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Search for "steroid" in Full Text gives 69 result(s) in Beilstein Journal of Organic Chemistry.
Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering
- Eric J. N. Helfrich,
- Geng-Min Lin,
- Christopher A. Voigt and
- Jon Clardy
Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283
- functional roles, which range from widely distributed metabolites like cholesterol, to those with more restricted distribution like vitamins A and D, carotenoids, and steroid hormones, to some with highly restricted distribution like pheromones, fragrances, and defense metabolites [2][3]. Many of the more
Graphical Abstract
Figure 1: Examples of bioactive terpenoids.
Figure 2: Repetitive electrophilic and nucleophilic functionalities in terpene and type II PKS-derived polyke...
Figure 3: Abundance and distribution of bacterial terpene biosynthetic gene clusters as determined by genome ...
Figure 4: Terpenoid biosynthesis. Terpenoid biosynthesis is divided into two phases, 1) terpene scaffold gene...
Figure 5: Mechanisms for type I, type II, and type II/type I tandem terpene cyclases. a) Tail-to-head class I...
Figure 6: Functional TC characterization. a) Different terpenes were produced when hedycaryol (18) synthase a...
Figure 7: Selected examples of terpene modification by bacterial CYPs. a) Hydroxylation [89]. b) Carboxylation, h...
Figure 8: Off-target effects observed during heterologous expression of terpenoid BGCs. Unexpected oxidation ...
Figure 9: TC promiscuity and engineering. a) Spata-13,17-diene (39) synthase (SpS) can take C15 and C25 oligo...
Figure 10: Substrate promiscuity and engineering of CYPs. a) Selected examples from using a CYP library to oxi...
Figure 11: Engineering of terpenoid pathways. a) Metabolic network of terpenoid biosynthesis. Toxic intermedia...
Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups
- Xiaowei Li,
- Xiaolin Shi,
- Xiangqian Li and
- Dayong Shi
Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218
- hydrocarbons, substituted cyclic molecules, terpenoids, and steroid derivatives, were selectively fluorinated at some otherwise inaccessible sites, however, in low to moderate yields. On the other hand, the same group [83] developed Mn(salen)Cl as a catalyst for the direct C–H fluorination at benzylic
Graphical Abstract
Scheme 1: The main three strategies of fluorination: nucleophilic, electrophilic and radical fluorination.
Scheme 2: Doyle’s Pd-catalyzed fluorination of allylic chlorides.
Scheme 3: Allylic fluorination of 2- and 3-substituted propenyl esters.
Scheme 4: Regioselective allylic fluorination of cinnamyl phosphorothioate esters.
Scheme 5: Palladium-catalyzed aliphatic C–H fluorination reported by Doyle.
Scheme 6: Pd-catalyzed enantioselective fluorination of α-ketoesters followed by stereoselective reduction to...
Scheme 7: Pd-catalyzed C(sp3)–H fluorination of oxindoles.
Scheme 8: C–H fluorination of 8-methylquinoline derivatives with F− reagents.
Scheme 9: Fluorination of α-cyano acetates reported by van Leeuwen.
Scheme 10: The catalytic enantioselective electrophilic C–H fluorination of α-chloro-β-keto phosphonates.
Scheme 11: Fluorination of unactivated C(sp3)–H bonds directed by the bidentate PIP auxiliary.
Scheme 12: Fluorination of C(sp3)–H bonds at the β-position of carboxylic acids.
Scheme 13: Enantioselective benzylic C–H fluorination with a chiral transient directing group.
Scheme 14: Microwave-heated Pd-catalyzed fluorination of aryl alcohols.
Scheme 15: Fluorination of aryl potassium trifluoroborates.
Scheme 16: C(sp2)–F bond formation using precatalyst [L·Pd]2(cod).
Scheme 17: Pd-catalyzed fluorination of (hetero)aryl triflates and bromides.
Scheme 18: The Pd-catalyzed C–H fluorination of arenes with Selectfluor/NFSI.
Scheme 19: Pd(II)-catalyzed ortho-monofluorination protocol for benzoic acids.
Scheme 20: Pd-catalyzed C(sp2)–H bond fluorination of 2-arylbenzothiazoles.
Scheme 21: Nitrate-promoted fluorination of aromatic and olefinic C(sp2)–H bonds and proposed mechanism.
Scheme 22: Fluorination of oxalyl amide-protected benzylamine derivatives.
Scheme 23: C–H fluorination of benzaldehydes with orthanilic acids as transient directing group.
Scheme 24: Pd(II)-catalyzed aryl C–H fluorination with various directing groups.
Scheme 25: Cu-catalyzed aliphatic, allylic, and benzylic fluorination.
Scheme 26: Cu-catalyzed SN2 fluorination of primary and secondary alkyl bromides.
Scheme 27: Copper-catalyzed fluorination of alkyl triflates.
Scheme 28: Cu-catalyzed fluorination of allylic bromides and chlorides.
Scheme 29: Synthetic strategy for the fluorination of active methylene compounds.
Scheme 30: Fluorination of β-ketoesters using a tartrate-derived bidentate bisoxazoline-Cu(II) complex.
Scheme 31: Highly enantioselective fluorination of β-ketoesters and N-Boc-oxindoles.
Scheme 32: Amide group-assisted site-selective fluorination of α-bromocarbonyl compounds.
Scheme 33: Cu-mediated aryl fluorination reported by Sanford [77].
Scheme 34: Mono- or difluorination reactions of benzoic acid derivatives.
Scheme 35: Cu-catalyzed fluorination of diaryliodonium salts with KF.
Scheme 36: Copper(I)-catalyzed cross-coupling of 2-pyridylaryl bromides.
Scheme 37: AgNO3-catalyzed decarboxylative fluorination of aliphatic carboxylic acids.
Scheme 38: The Mn-catalyzed aliphatic and benzylic C–H fluorination.
Scheme 39: Iron(II)-promoted C–H fluorination of benzylic substrates.
Scheme 40: Ag-catalyzed fluorodecarboxylation of carboxylic acids.
Scheme 41: Vanadium-catalyzed C(sp3)–H fluorination.
Scheme 42: AgNO3-catalyzed radical deboronofluorination of alkylboronates and boronic acids.
Scheme 43: Selective heterobenzylic C–H fluorination with Selectfluor reported by Van Humbeck.
Scheme 44: Fe(II)-catalyzed site-selective fluorination guided by an alkoxyl radical.
Scheme 45: Fluorination of allylic trichloroacetimidates reported by Nguyen et al.
Scheme 46: Iridium-catalyzed fluorination of allylic carbonates with TBAF(t-BuOH)4.
Scheme 47: Iridium-catalyzed asymmetric fluorination of allylic trichloroacetimidates.
Scheme 48: Cobalt-catalyzed α-fluorination of β-ketoesters.
Scheme 49: Nickel-catalyzed α-fluorination of various α-chloro-β-ketoesters.
Scheme 50: Ni(II)-catalyzed enantioselective fluorination of oxindoles and β-ketoesters.
Scheme 51: Scandium(III)-catalyzed asymmetric C–H fluorination of unprotected 3-substituted oxindoles.
Scheme 52: Iron-catalyzed directed C–H fluorination.
Scheme 53: Electrophilic silver-catalyzed Ar–F bond-forming reaction from arylstannanes.
Figure 1: Nucleophilic, electrophilic and radical CF3 sources.
Scheme 54: Cu(I)-catalyzed allylic trifluoromethylation of unactivated terminal olefins.
Scheme 55: Direct copper-catalyzed trifluoromethylation of allylsilanes.
Scheme 56: Cupper-catalyzed enantioselective trifluoromethylation of five and six-membered ring β-ketoesters.
Scheme 57: Cu-catalyzed highly stereoselective trifluoromethylation of secondary propargyl sulfonates.
Scheme 58: Remote C(sp3)–H trifluoromethylation of carboxamides and sulfonamides.
Scheme 59: Trifluoromethylation of allylsilanes with photoredox catalysis.
Scheme 60: Ag-catalyzed decarboxylative trifluoromethylation of aliphatic carboxylic acids in aqueous CH3CN.
Scheme 61: Decarboxylative trifluoromethylation of aliphatic carboxylic acids via combined photoredox and copp...
Scheme 62: Palladium-catalyzed Ar–CF3 bond-forming reaction.
Scheme 63: Palladium-catalyzed trifluoromethylation of arenes with diverse heterocyclic directing groups.
Scheme 64: Pd-catalyzed trifluoromethylation of indoles as reported by Liu.
Scheme 65: Pd-catalyzed trifluoromethylation of vinyl triflates and vinyl nonaflates.
Scheme 66: Pd(II)-catalyzed ortho-trifluoromethylation of aromatic C–H bonds.
Scheme 67: Visible-light-induced Pd(OAc)2-catalyzed ortho-trifluoromethylation of acetanilides with CF3SO2Na.
Scheme 68: CuI-catalyzed trifluoromethylation of aryl- and alkenylboronic acids.
Scheme 69: Cu-catalyzed trifluoromethylation of aryl- and vinylboronic acids.
Scheme 70: Copper-catalyzed trifluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 71: Formation of C(sp2)–CF3 bond catalyzed by copper(I) complex.
Scheme 72: Loh’s Cu(I)-catalyzed trifluoromethylation of enamides and electron-deficient alkenes.
Scheme 73: Copper and iron-catalyzed decarboxylative tri- and difluoromethylation.
Scheme 74: Cu-catalyzed trifluoromethylation of hydrazones developed by Bouyssi.
Scheme 75: Cu(I)-catalyzed trifluoromethylation of terminal alkenes.
Scheme 76: Cu/Ag-catalyzed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 77: Copper-catalyzed direct alkenyl C–H trifluoromethylation.
Scheme 78: Copper(I/II)-catalyzed direct trifluoromethylation of styrene derivatives.
Scheme 79: Regioselective trifluoromethylation of pivalamido arenes and heteroarenes.
Scheme 80: Synthesis of trifluoromethylquinones in the presence of copper(I).
Scheme 81: Oxidative trifluoromethylation of imidazoheterocycles in ionic liquid/water.
Scheme 82: A mild and fast continuous-flow trifluoromethylation of coumarins using a CuI/CF3SO2Na/TBHP system.
Scheme 83: Copper-catalyzed oxidative trifluoromethylation of various 8-aminoquinolines.
Scheme 84: PA-directed copper-catalyzed trifluoromethylation of anilines.
Scheme 85: Trifluoromethylation of potassium vinyltrifluoroborates catalyzed by Fe(II).
Scheme 86: Alkenyl trifluoromethylation catalyzed by Ru(phen)3Cl2 as photocatalyst.
Scheme 87: Ru-catalyzed trifluoromethylation of alkenes by Akita’s group.
Scheme 88: Ir-catalyzed Cvinyl–CF3 bond formation of α,β-unsaturated carboxylic acids.
Scheme 89: Ag(I)-catalyzed denitrative trifluoromethylation of β-nitrostyrenes.
Scheme 90: Photocatalyzed direct trifluoromethylation of aryl and heteroaryl C–H bonds.
Scheme 91: Rhenium (MTO)-catalyzed direct trifluoromethylation of aromatic substrates.
Scheme 92: Trifluoromethylation of unprotected anilines under [Ir(ppy)3] catalyst.
Scheme 93: Oxidative trifluoromethylation of imidazopyridines and imidazoheterocycles.
Scheme 94: Ruthenium-catalyzed trifluoromethylation of (hetero)arenes with trifluoroacetic anhydride.
Scheme 95: Phosphovanadomolybdic acid-catalyzed direct C–H trifluoromethylation.
Scheme 96: Picolinamide-assisted ortho-trifluoromethylation of arylamines.
Scheme 97: A nickel-catalyzed C–H trifluoromethylation of free anilines.
Scheme 98: Cu-mediated trifluoromethylation of terminal alkynes reported by Qing.
Scheme 99: Huang’s C(sp)–H trifluoromethylation using Togni’s reagent.
Scheme 100: Cu-catalyzed methods for trifluoromethylation with Umemoto’s reagent.
Scheme 101: The synthesis of alkynyl-CF3 compounds in the presence of fac-[Ir(ppy)3] under visible-light irradi...
Scheme 102: Pd-catalyzed Heck reaction reported by Reutrakul.
Scheme 103: Difluoromethylation of enamides and ene-carbamates.
Scheme 104: Difluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 105: Copper-catalyzed direct C(sp2)–H difluoroacetylation reported by Pannecoucke and co-workers.
Scheme 106: Difluoroalkylation of aldehyde-derived hydrazones with functionalized difluoromethyl bromides.
Scheme 107: Photoredox-catalyzed C–H difluoroalkylation of aldehyde-derived hydrazones.
Scheme 108: Synergistic ruthenium(II)-catalyzed C–H difluoromethylation reported by Ackermann.
Scheme 109: Visible-light photocatalytic decarboxylation of α,β-unsaturated carboxylic acids.
Scheme 110: Synthesis of difluorinated ketones via S-alkyl dithiocarbamates obtained from acyl chlorides and po...
Scheme 111: Synthesis of aryl and heteroaryl difluoromethylated phosphonates.
Scheme 112: Difluoroalkylation of secondary propargyl sulfonates using Cu as the catalyst.
Scheme 113: Ru(II)-mediated para-selective difluoromethylation of anilides and their derivatives.
Scheme 114: Bulky diamine ligand promoted cross-coupling of difluoroalkyl bromides.
Scheme 115: Copper-catalyzed C3–H difluoroacetylation of quinoxalinones.
Scheme 116: Copper(I) chloride-catalyzed trifluoromethylthiolation of enamines, indoles and β-ketoesters.
Scheme 117: Copper-boxmi-catalyzed asymmetric trifluoromethylthiolation of β-ketoesters.
Scheme 118: Direct Cu-catalyzed trifluoromethylthiolation of boronic acids and alkynes.
Scheme 119: Cu-catalyzed synthesis of α-trifluoromethylthio-substituted ketones.
Scheme 120: Trifluoromethylthiolation reactions promoted by diazotriflone and copper.
Scheme 121: Halide activation of N-(trifluoromethylthio)phthalimide.
Scheme 122: The visible light-promoted trifluoromethylthiolation reported by Glorius.
Scheme 123: Synthesis of α-trifluoromethylthioesters via Goossen’s approach.
Scheme 124: Photoinduced trifluoromethylthiolation of diazonium salts.
Scheme 125: Ag-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.
Scheme 126: Catalytic (hetero)aryl C–H trifluoromethoxylation under visible light.
Scheme 127: Photoinduced C–H-bond trifluromethoxylation of (hetero)arenes.
1,2,3-Triazolium macrocycles in supramolecular chemistry
- Mastaneh Safarnejad Shad,
- Pulikkal Veettil Santhini and
- Wim Dehaen
Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211
- macrocycles are a class of steroid-based receptors which can host polar molecules in nonpolar solvents because of their amphiphilic nature. As a result, their design and synthesis has been a topic of substantial research interest in supramolecular chemistry [32][33]. Various synthetic methods have been
Graphical Abstract
Figure 1: Hydrogen, halogen or chalcogen bonding to anions within a bistriazolium macrocycle.
Figure 2: Main synthetic strategies towards macrocyclic triazoliums.
Figure 3: Chemical structure of compound 1 (1a, 1b and 1c) and 2.
Figure 4: Chemical structure of compound 3 and 4.
Figure 5: Chemical structure of compound 5.
Figure 6: Chemical structure of compound 6.
Figure 7: Chemical structure of compound 7.
Figure 8: Chemical structure of compound 8.
Figure 9: Chemical structures of compound 9.
Figure 10: Chemical structures of compound 10, 11 and 12.
Figure 11: Chemical structure of compound 13.
Figure 12: Chemical structure of compound 15 including the sigma-connected TCNQ dimer.
Figure 13: Chemical structure of compound 16 for the kinetic resolution of epoxides.
Figure 14: Chemical structure of compound 17a (bisnaphtho crown ether shown).
Figure 15: Jump rope in molecular double-lasso compounds 18.
Figure 16: Chemical structure of compound 19 and acid–base triggered motions.
Steroid diversification by multicomponent reactions
- Leslie Reguera,
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Daniel G. Rivera
Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121
- materials for relevant MCRs such as those based on imine and isocyanide. The focus is mainly posed on proving the amenability of MCRs for the diversity-oriented derivatization of naturally occurring steroids and the construction of complex steroid-based platforms for drug discovery, chemical biology and
- steroid biological functions. Such oxygenated and alkene groups represent the entrance door for subsequent synthetic modifications, including the incorporation of MCR reactive functionalities. In the last two decades, MCRs have emerged as effective tools for the rapid derivatization of steroidal skeletons
- with steroids. Herein, we provide a comprehensive review describing – to our understanding – the most important inputs of the utilization of MCRs in the structural diversification of steroids. The review is divided in different aspects of steroid chemistry, such as modification of the side chain and
Graphical Abstract
Figure 1: Structures of natural steroids of A) animal and B) plant origin.
Scheme 1: Synthesis of a steroidal β-lactam by Ugi reaction of a cholanic aldehyde [14].
Scheme 2: Synthetic route to steroidal 2,5-diketopiperazines based on a diastereoselective Ugi-4CR with an an...
Scheme 3: Multicomponent synthesis of a heterocycle–steroid hybrid using a ketosteroid as carbonyl component [18]....
Scheme 4: Synthesis of peptidomimetic–steroid hybrids using the Ugi-4CR with spirostanic amines and carboxyli...
Scheme 5: Synthesis of azasteroids using the Ugi-4CR with androstanic and pregnanic carboxylic acids [22].
Figure 2: Ugi-4CR-derived library of androstanic azasteroids with diverse substitution patterns at the phenyl...
Scheme 6: Synthesis of 4-azacholestanes by an intramolecular Ugi-4C-3R [26].
Scheme 7: Synthesis of amino acid–steroid hybrid by multiple Ugi-4CR using steroidal isocyanides [29].
Scheme 8: Synthesis of ecdysteroid derivatives by Ugi-4CR using a steroidal isocyanide [30].
Scheme 9: Stereoselective multicomponent synthesis of a steroid–tetrahydropyridine hybrid using a chiral bifu...
Scheme 10: Pd(II)-catalyzed three-component reaction with an alkynyl seco-cholestane [34].
Scheme 11: Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36].
Scheme 12: Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37,38].
Scheme 13: Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli-3CR [39,42,43].
Scheme 14: Synthesis of steroidal pyridopyrimidines by a reaction sequence comprising a 4CR followed by a post...
Scheme 15: Synthesis of steroid-fused pyrimidines by MCR of 2-hydroxymethylene-3-ketosteroids [46].
Scheme 16: Synthesis of steroid-fused naphthoquinolines by the Kozlov–Wang MCR using ketosteroids [50,51].
Scheme 17: Conjugation of steroids to carbohydrates and peptides by the Ugi-4CR [62,63].
Scheme 18: Solid-phase multicomponent conjugation of peptides to steroids by the Ugi-4CR [64].
Scheme 19: Solid-phase multicomponent conjugation of peptides to steroids by the Petasis-3CR [68].
Scheme 20: Synthesis of steroidal macrobicycles (cages) by multiple multicomponent macrocyclizations based on ...
Scheme 21: One-pot synthesis of steroidal cages by double Ugi-4CR-based macrocyclizations [76].
Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions
- Angélica de Fátima S. Barreto and
- Carlos Kleber Z. Andrade
Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88
- chimeric peptoid macrocycles containing steroid moieties [37]. The process was based on designing a 4-fold Ugi-4CR macrocyclization by using the steroidal diisocyanide 107 with diacid 108 or diamine 109 (Scheme 21). According to the authors, this was the first report of repetitive multicomponent reactions
- approach provided the synthesis of steroid-biaryl ether hybrid macrocycles 117 and 118 with up to 68 members by the MiBs strategy. Another representative example of MiBs is the synthesis of the biaryl ether-containing macrocycles 123a–f (Scheme 23) [39]. The synthetic strategy involved the mixing of three
- [41] performed the first use of the diamine/diacid combination of bidirectional Ugi-MiBs in the synthesis of novel steroid–peptoid hybrid macrocycles. Scheme 25 shows two examples using this combination for the synthesis of cholane–peptoid hybrid macrocycles. Another application of the MiBs approach
Graphical Abstract
Scheme 1: Comparison between a normal sequential reaction and an MCR.
Scheme 2: Synthesis of tetrazoles and hydantoinimide derivatives by consecutive Ugi reactions [17].
Scheme 3: Synthesis of tetrazole-ketopiperazines by two consecutive Ugi reactions [19].
Scheme 4: Synthesis of acylhydrazino bis(1,5-disubstituted tetrazoles) through two hydrazine-Ugi-azide reacti...
Scheme 5: Synthesis of substituted α-aminomethyltetrazoles through two consecutive Ugi reactions (U-4CR and U...
Scheme 6: Synthesis of tetrazole peptidomimetics by direct use of amino acids in two consecutive Ugi reaction...
Scheme 7: One-pot 8CR based on 3 sequential IMCRs [25].
Scheme 8: Combination of IMCRs for the synthesis of substituted 2H-imidazolines [25].
Scheme 9: 6CR involving a tandem combination of Groebke–Blackburn–Bienaymé and Ugi reaction for the synthesis...
Scheme 10: 5CR involving a tandem combination of Groebke–Blackburn–Bienaymé and Passerini reaction for the syn...
Scheme 11: Synthesis of tubugis via three consecutive IMCRs [27].
Scheme 12: Synthesis of telaprevir through consecutive IMCRs [28].
Scheme 13: Another synthesis of telaprevir through consecutive IMCRs [29].
Scheme 14: a) Synthetic sequence for accessing diverse macrocycles containing the tetrazole nucleus by the uni...
Scheme 15: a) Synthetic sequence for the tetrazolic macrocyclic depsipeptides using a combination of two IMCRs...
Scheme 16: Synthesis of cyclic pentapeptoids by consecutive Ugi reactions [32].
Scheme 17: Synthesis of a cyclic pentapeptoid by consecutive Ugi reactions [32].
Scheme 18: MW-mediated synthesis of a cyclopeptoid by consecutive Ugi reactions [33].
Scheme 19: Synthesis of six cyclic pentadepsipeptoids via consecutive isocyanide-based IMCRs [34].
Scheme 20: Microwave-mediated synthesis of a cyclic heptapeptoid through four consecutive IMCRs [35].
Scheme 21: Macrocyclization of bifunctional building blocks containing diacid/diisonitrile and diamine/diisoni...
Scheme 22: Synthesis of steroid-biaryl ether hybrid macrocycles by MiBs [38].
Scheme 23: Synthesis of biaryl ether-containing macrocycles by MiBs [39].
Scheme 24: Synthesis of natural product-inspired biaryl ether-cyclopeptoid macrocycles [40].
Scheme 25: Synthesis of cholane-based hybrid macrolactams by MiBs [41].
Scheme 26: Synthesis of macrocyclic oligoimine-based DCL using the Ugi-4CR-based quenching approach [42].
Scheme 27: Dye-modified and photoswitchable macrocycles by MiBs [43].
Scheme 28: Synthesis of nonsymmetric cryptands by two sequential double Ugi-4CR-based macrocyclizations [44].
Scheme 29: Synthesis of steroid–aryl hybrid cages by sequential 2- and 3-fold Ugi-4CR-based macrocyclizations [46]....
Scheme 30: Ugi-MiBs approach towards natural product-like macrocycles [47].
Scheme 31: a) Bidirectional macrocyclization of peptides by double Ugi reaction. b) Ugi-4CR for the generation...
Scheme 32: MiBs based on the Passerini-3CR for the synthesis of macrolactones [49].
Scheme 33: Template-driven approach for the synthesis of macrotricycles 170 [50].
Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials
- Patrycja Żak and
- Cezary Pietraszuk
Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28
- research, active in preliminary tests and commercially available second generation Grubbs–Hoveyda catalyst Ru-3 and its nitro derivative Ru-4 were selected. The same authors were able to successfully functionalize allylsilsesquioxane with more challenging, three different steroid derivatives. The reactions
Graphical Abstract
Figure 1: Cubic octasilsesquioxane.
Scheme 1: Reactivity of vinylsilanes in the presence of ruthenium alkylidene complexes; a) cross metathesis, ...
Figure 2: The scope and limitations of metathesis in transformations of vinyl-substituted siloxanes and silse...
Scheme 2: Application of olefin metathesis in the synthesis and modification of POSS-based materials: a) func...
Figure 3: Olefin metathesis catalysts used in transformations of silsesquioxanes.
Figure 4: Octavinyl-substituted cubic silsesquioxane (OVS) and spherosilicate.
Scheme 3: Cross metathesis of OVS with terminal olefins (stereoselectivity as discussed in the text).
Scheme 4: Cross metathesis of OVS with substituted styrenes.
Scheme 5: Modification of OVS via CM with styrenes.
Figure 5: Vinylbiphenyl chromophore-decorated cubic silsesquioxanes.
Scheme 6: Cross metathesis of OVS with carboranylstyrene.
Scheme 7: Synthesis of octakis[2-(p-carboxyphenyl)ethyl]silsesquioxane via CM and subsequent hydrogenation.
Scheme 8: Cross metathesis of monovinyl-POSS with olefins.
Scheme 9: Cross metathesis of monovinyl-POSS with highly π-conjugated substituted styrenes.
Scheme 10: Cross metathesis of monovinylgermasilsesquioxane with styrenes.
Scheme 11: Cross metathesis of DDSQ-2SiVi with olefins.
Scheme 12: Cross metathesis of DDSQ-2SiVi with substituted styrenes.
Scheme 13: Cross metathesis of (DDSQ-2GeVi) with olefins.
Scheme 14: CM of divinyl-substituted T10 and T12 with 4-bromostyrene (selected isomers are shown).
Scheme 15: Synthesis of vinylstilbene derivatives of T10 and T12 via a sequence of CM and Heck coupling.
Scheme 16: Cross metathesis of allyl-POSS with tert-butyl acrylate and (Z)-1,4-diacetoxy-but-2-ene.
Scheme 17: Cross metathesis of allyl-POSS with olefins.
Scheme 18: Acyclic diene metathesis copolymerization of DDSQ-2SiVi with diolefins.
Scheme 19: Acyclic diene metathesis copolymerization of DDSQ-2GeVi with diolefins.
Scheme 20: Ring-opening metathesis copolymerization of norbornenylethyl-POSS with norbornene.
Scheme 21: Synthesis of a polyethylene–POSS copolymer via ring-opening metathesis copolymerization of norborne...
Scheme 22: ROMP of norbornenylethyl-POSS with 1,5-cyclooctadiene.
Scheme 23: Copolymerization of POSS-functionalized norbornene with DCPD.
Scheme 24: Copolymerization of tris(norbornenylethyl)-POSS with DCPD.
Scheme 25: Copolymerization of N-(propyl-POSS)-7-oxanorbornene-5,6-dicarboximide with 3-(trifluoromethyl)pheny...
Figure 6: Homopolymers and copolymers having POSS groups attached to the main chain via flexible spacers of d...
Scheme 26: Ring-opening metathesis copolymerization of POSS-NBE with methyltetracyclododecene.
Scheme 27: Synthesis of block copolymer via ROMP by sequential monomer addition.
Scheme 28: Synthesis of a liquid crystalline polymer with POSS core in the side chain.
Scheme 29: Sequential synthesis of copolymers of polynorbornene containing POSS and PEO pendant groups.
Scheme 30: Synthesis of rodlike POSS−bottlebrush block copolymers [54].
Scheme 31: Surface-initiated ROMP producing copolymer layers on the surface of CdSe/ZnS quantum dots.
Degenerative xanthate transfer to olefins under visible-light photocatalysis
- Atsushi Kaga,
- Xiangyang Wu,
- Joel Yi Jie Lim,
- Hirohito Hayashi,
- Yunpeng Lu,
- Edwin K. L. Yeow and
- Shunsuke Chiba
Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283
- functionalized cyclopentane 3an and pyrrolidine 3ao, respectively, via 5-exo-trig radical cyclization (Table 2, entries 13 and 14). The present method was capable in functionalizing olefins 2p and 2q installed on steroid scaffolds with high efficiency (Table 2, entries 15 and 16). We next examined the reactions
Graphical Abstract
Scheme 1: Degenerative radical transfer of xanthates to olefins.
Scheme 2: Photocatalytic RAFT polymerization of xanthate 4.
Figure 1: Photoluminescence (PL) spectra of the 3MLCT state of 8 in degassed DMSO solvent with (A) various co...
Figure 2: (A) ns-Transient absorption spectra of photocatalyst 8 in degassed DMSO recorded at different delay...
Figure 3: UV–vis absorption spectrum of 1a (1 mM solution in DMSO).
Scheme 3: Determination of quantum yield.
Scheme 4: Proposed reaction mechanism.
Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors
- Rebeka Jójárt,
- Szabolcs Pécsy,
- György Keglevich,
- Mihály Szécsi,
- Réka Rigó,
- Csilla Özvegy-Laczka,
- Gábor Kecskeméti and
- Erzsébet Mernyák
Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262
- -benzyl ether function displayed substantial submicromolar OATP2B1 inhibitory activity. The inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by in vitro radiosubstrate incubation methods. None of
- large circulatory reservoir catalyzed by steroid sulfatase (STS), is one of the major alternative sources of prehormone estrone for the local supply of estrogens [2]. The availability of free estrone on the cellular level depends on the expression of STS and/or SULT, which catalyze the sulfation of the
- reduction of the 17-oxo function leading to 17β-estradiol. This last step of the estrogen biosynthesis is catalyzed by the 17β-hydroxy steroid dehydrogenase type 1 isoenzyme (17β-HSD1) [13]. Thus STS and 17β-HSD1 became important drug targets in estrogen-dependent diseases [1][14]. Their inhibition could be
Graphical Abstract
Scheme 1: Pd-catalyzed C(sp2)–P couplings at C-2 or C-4 in the 13α-estrone series.
The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series
- Ildikó Bacsa,
- Dávid Szemerédi,
- János Wölfling,
- Gyula Schneider,
- Lilla Fekete and
- Erzsébet Mernyák
Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85
- -natural C-18 steroid containing cis junction of rings C and D [21][22]. This core-modified compound differs from its natural 13β counterpart not only in the configuration of C-13, but also its more flexible conformation. Poirier et al. investigated the in vitro and in vivo estrogenic activity of 3,17
Graphical Abstract
Scheme 1: Pd-catalyzed aminations at C-2 or C-4 in the 13α-estrone series. Reactions were performed on a 0.25...
Scheme 2: Two-step synthesis of 2-amino-13α-estra-1,3,5(10)-trien-17-one (13).
On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site
- Eirinaios I. Vrettos,
- Gábor Mező and
- Andreas G. Tzakos
Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80
- , present on the cell surface of the targeted tissues and not within their cytosol or nucleus (i.e., steroid receptors [33]). The selected receptor should be uniquely expressed or overexpressed on cancer cells (usually 3-fold or higher in comparison with normal cells). Additionally, it should be expressed
Graphical Abstract
Figure 1: Conventional chemotherapy versus targeted chemotherapy. Black color = Solid malignant tumor; red = ...
Figure 2: A. General structural architecture of the ideal navigated drug delivery system [31]. B. General structu...
Figure 3: Binding and penetration mechanism of iRGD. The iRGD peptide is accumulated on the surface of αv int...
Figure 4: Representative examples of anticancer drugs utilized for the construction of PDCs. The most usual c...
Figure 5: Illustration of the drug release mechanism from the self-immolative spacer PABC conjugated to a tum...
Figure 6: Structures of the PDCs named AN-152 and AN-207.
Figure 7: Structure of the PDC named AN-238.
Figure 8: Chemical structure and synthetic scheme for the PDC ANG1005. (A) ANG1005 is composed of three molec...
Figure 9: Structure of oxime linked Dau–GnRH-III conjugate with or without cathepsin B labile spacer and thei...
Figure 10: Synthesis of the most effective GnRH-III–Dau conjugate with two drug molecules [153].
Figure 11: Structures of the four different PDCs of D-Lys6-GnRH-I and gemcitabine (GSG, GSG2, 3G, 3G2) [19].
Figure 12: Structures of (A) native sunitinib; (B) SAN1 analog of sunitinib and (C) assembled PDC named SAN1GS...
Figure 13: Synthetic scheme for the formation of GSG and the unexpected side product [156].
Figure 14: Illustration of uncharted guanidinium peptide coupling reagent side reactions during PDCs synthesis ...
Figure 15: Putative mechanism for the formation of the uronium side product [156].
Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies
- Elias Christoforides,
- Andreas Papaioannou and
- Kostas Bethanis
Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69
- inclusion compound remains very stable in aqueous solution at both temperatures. Keywords: beta-cyclodextrin; cholesterol; crystal structure; molecular dynamics; Introduction Cholesterol ((3β)-cholest-5-en-3-ol, CHL, Figure 1a) is a polycyclic steroid that is synthesized in mammalian cells and has a
- significant role in biology as an essential structural component of the cell walls and as precursor for the biosynthesis of several substances such as vitamin D, bile acids and steroid hormones. However, the consumption of food rich in cholesterol like meat, eggs and dairy products has been associated with
Graphical Abstract
Figure 1: Schematic representation of (a) the cholesterol molecule; (b) the β-cyclodextrin molecule.
Figure 2: (a) Crystal structure of the inclusion compound of cholesterol in β-CD dimer. Water molecules are o...
Figure 3: RMSD over time for all CHL (green) and β-CD (blue) atoms (a) at 300 K and (b) at 340 K.
Figure 4: Representative snapshots of the CHL/β-CD inclusion complex at 0 (a, c) and 11 ns (b, d) in timescal...
Figure 5: (a) Distance between the O1 atom (CHL) and the centroid DK of the O4n atoms of host A at 300 (green...
Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review
- Fabio Tonin and
- Isabel W. C. E. Arends
Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33
- reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each
- secondary bile acid. It is produced by bacteria in the colon from CDCA trough the dehydroxylation of the C7 functional group of the steroid framework. Low percentages of other secondary bile acids and related keto derivatives can be found in the bile. The solubility properties, interactions and metabolisms
- are related to the position and stereochemistry of the hydroxy groups attached to the steroid ring. A general structure with the names of several bile acids is reported in Figure 2. Deconjugation Free bile acids can be obtained from the corresponding bile amides (with glycine and taurine) through a
Graphical Abstract
Figure 1: Chemical structure of UDCA.
Figure 2: Chemical structures of bile acids and salts.
Figure 3: Comparison between Wolff–Kishner and Mozingo reduction. Notably the overall chemical reaction is th...
Figure 4: Reaction catalysed by the 12α-HSDH; the 12-OH group of CA or UCA is oxidized yielding 12-oxo-CDCA o...
Figure 5: Epimerization reaction catalysed by the 7α-HSDH and 7β-HSDH; the 7α-OH group of CA (R = OH) or CDCA...
Figure 6: Overview of the chemoenzymatic process for the production of UDCA from CA: The oxidation, reduction...
Figure 7: Schematic representation of the flow reactor for the continuous conversion of CDCA to UDCA [93].
Figure 8: Chemoenzymatic pathways for the formation of UDCA from CA that profit by the C7 hydroxylation activ...
Synthesis of ergostane-type brassinosteroids with modifications in ring A
- Vladimir N. Zhabinskii,
- Darya A. Osiyuk,
- Yuri V. Ermolovich,
- Natalia M. Chaschina,
- Tatsiana S. Dalidovich,
- Miroslav Strnad and
- Vladimir A. Khripach
Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229
- ; metabolites; Introduction The group of steroid plant hormones called brassinosteroids (BS) currently comprises about 70 compounds [1]. It is generally accepted that only few of them (such as brassinolide, castasterone, epibrassinolide, etc.), possessing 2α,3α-, (22R,23R)-diol groups, B-lactone, and 6-ketone
Graphical Abstract
Scheme 1: Structural features of epicastasterone (1), epibrassinolide (2) and A-ring units 3–12 of BS biosynt...
Scheme 2: (a) Ac2O, Py, DMAP, 60 °C; (b) K2CO3, MeOH, 20 °C (97% over 2 steps); (c) TCDI, DMAP, THF, 65 °C (7...
Scheme 3: (a) MsCl, Py, 20 °C (95%); (b) Zn, NaI, DMF, 150 °C (83%); (c) KOH, MeOH, 65 °C (96%).
Scheme 4: (a) MCPBA, CH2Cl2, 20 °C (90%); (b) NBS, DME, 20 °C; (c) KOH, MeOH, 20 °C (85% over 2 steps).
Scheme 5: (a) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (94%); (b) PCC, CH2Cl2, 20 °C (84%); (c) H2, Pd/C, 20 °...
Scheme 6: (a) TsCl, DMAP, Py, 30 °C (91%); (b) Py, 115 °C (65%); (c) KOH, MeOH, 20 °C (52%).
Scheme 7: (a) NaBH4, EtOH, −25 °C (49%); (b) KOH, MeOH, 65 °C (85%).
Scheme 8: (a) Anisaldehyde, TMSCl, MeOH, 20 °C; (b) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (86% over 2 steps...
Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity
- Henryk Myszka,
- Patrycja Sokołowska,
- Agnieszka Cieślińska,
- Andrzej Nowacki,
- Maciej Jaśkiewicz,
- Wojciech Kamysz and
- Beata Liberek
Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227
- the obtained compounds are active against Gram-positive bacteria and Candida type fungi. Keywords: antimicrobial activities; D-galactosamine; diosgenin; glycosylation; saponin; tetrachlorophthalimido derivatives; Introduction Saponins are steroid or triterpenoid glycosides found in various plants [1
Graphical Abstract
Scheme 1: Synthesis of diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside (4).
Figure 1: Derivatives of diosgenyl glycosides 5–13.
Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective
- Yaroslav D. Boyko,
- Valentin S. Dorokhov,
- Alexey Yu. Sukhorukov and
- Sema L. Ioffe
Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220
- exploited the Michael addition of enolates to nitrosoalkenes in their studies towards syntheses of 3-methoxy-9β-estra(1,3,5(10))trien(11,17)dione (25) (1977) [31] and (+/−)-isocomene (1981) [32]. The key carbon–carbon bond formation step in the synthesis of steroid 25 was the stereoselective reaction of α
- hydrolysis of the oximino group gave target steroid 25 with the desired configuration of all stereogenic centers. In the attempted route to (+/−)-isocomene, Oppolzer and co-workers suggested pentalenone 29, accessible by an intramolecular aldol condensation/elimination of diketone 30, as a key precursor
Graphical Abstract
Scheme 1: Precursors of nitrosoalkenes NSA.
Scheme 2: Reactions of cyclic α-chlorooximes 1 with 1,3-dicarbonyl compounds.
Scheme 3: C-C-coupling of N,N-bis(silyloxy)enamines 3 with 1,3-dicarbonyl compounds.
Scheme 4: Reaction of N,N-bis(silyloxy)enamines 3 with nitronate anions.
Scheme 5: Reaction of α-chlorooximes TBS ethers 2 with ester enolates.
Scheme 6: Assembly of bicyclooctanone 14 via an intramolecular cyclization of nitrosoalkene NSA2.
Scheme 7: A general strategy for the assembly of bicyclo[2.2.1]heptanes via an intramolecular cyclization of ...
Scheme 8: Stereochemistry of Michael addition to cyclic nitrosoalkene NSA3.
Scheme 9: Stereochemistry of Michael addition to acyclic nitrosoalkenes NSA4.
Scheme 10: Stereochemistry of Michael addition to γ-alkoxy nitrosoalkene NSA5.
Scheme 11: Oppolzer’s total synthesis of 3-methoxy-9β-estra(1,3,5(10))trien(11,17)dione (25).
Scheme 12: Oppolzer’s total synthesis of (+/−)-isocomene.
Figure 1: Alkaloids synthesized using stereoselective Michael addition to conjugated nitrosoalkenes.
Scheme 13: Weinreb’s total synthesis of alstilobanines A, E and angustilodine.
Scheme 14: Weinreb’s approach to the core structure of apparicine alkaloids.
Scheme 15: Weinreb’s synthesis of (+/−)-myrioneurinol via stereoselective conjugate addition of malonate to ni...
Scheme 16: Reactions of cyclic α-chloro oximes with Grignard reagents.
Scheme 17: Corey’s synthesis of (+/−)-perhydrohistrionicotoxin.
Scheme 18: Addition of Gilman’s reagents to α,β-epoxy oximes 53.
Scheme 19: Addition of Gilman’s reagents to α-chlorooximes.
Scheme 20: Reaction of silyl nitronate 58 with organolithium reagents via nitrosoalkene NSA12.
Scheme 21: Reaction of β-ketoxime sulfones 61 and 63 with lithium acetylides.
Scheme 22: Electrophilic addition of nitrosoalkenes NSA14 to electron-rich arenes.
Scheme 23: Addition of nitrosoalkenes NSA14 to pyrroles and indoles.
Scheme 24: Reaction of phosphinyl nitrosoalkenes NSA15 with indole.
Scheme 25: Reaction of pyrrole with α,α’-dihalooximes 70.
Scheme 26: Synthesis of indole-derived psammaplin A analogue 72.
Scheme 27: Synthesis of tryptophanes by reduction of oximinoalkylated indoles 68.
Scheme 28: Ottenheijm’s synthesis of neoechinulin B analogue 77.
Scheme 29: Synthesis of 1,2-dihydropyrrolizinones 82 via addition of pyrrole to ethyl bromopyruvate oxime.
Scheme 30: Kozikowski’s strategy to indolactam-based alkaloids via addition of indoles to ethyl bromopyruvate ...
Scheme 31: Addition of cyanide anion to nitrosoalkenes and subsequent cyclization to 5-aminoisoxazoles 86.
Scheme 32: Et3N-catalysed addition of trimethylsilyl cyanide to N,N-bis(silyloxy)enamines 3 leading to 5-amino...
Scheme 33: Addition of TMSCN to allenyl N-siloxysulfonamide 89.
Scheme 34: Reaction of nitrosoallenes NSA16 with malodinitrile and ethyl cyanoacetic ester.
Scheme 35: [4 + 1]-Annulation of nitrosoalkenes NSA with sulfonium ylides 92.
Scheme 36: Reaction of diazo compounds 96 with nitrosoalkenes NSA.
Scheme 37: Tandem Michael addition/oxidative cyclization strategy to isoxazolines 100.
Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly
- Weizhun Yang,
- Bo Yang,
- Sherif Ramadan and
- Xuefei Huang
Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207
- utilized glycosyl sulfoxide donors for glycosylation of unreactive substrates such as steroid derivative 2 by the Kahne group [25]. The axial C-7 hydroxy group in 2 is sterically hindered due to unfavorable 1,3-diaxial interactions. The traditional premixed glycosylation gave only low yields (<30%) of the
Graphical Abstract
Scheme 1: a) Traditional glycosylation typically employs the premixed approach with both the donor and the ac...
Scheme 2: Glycosylation of an unreactive substrate. Reagents and conditions: (a) Tf2O, −78 °C, CH2Cl2 (DCM), ...
Scheme 3: Bromoglycoside-mediated glycosylation.
Scheme 4: Glycosyl bromide-mediated selenoglycosyl donor-based iterative glycosylation. Reagents and conditio...
Scheme 5: Preactivation-based glycosylation using 2-pyridyl glycosyl donors.
Scheme 6: Chemoselective dehydrative glycosylation. Reagents and conditions: (a) Ph2SO, Tf2O, 2-chloropyridin...
Figure 1: Representative structures of products formed by the preactivation-based dehydrative glycosylation o...
Scheme 7: Possible mechanism for the dehydrative glycosylation. (a) Formation of diphenyl sulfide bis(triflat...
Scheme 8: Chemoselective iterative dehydrative glycosylation. Reagents and conditions: (a) Ph2SO, Tf2O, 2,4,6...
Scheme 9: Chemoselective iterative dehydrative glycosylation. Reagents and conditions: (a) Ph2SO, Tf2O, −40 °...
Scheme 10: Chemical synthesis of a hyaluronic acid (HA) trimer 47. Reagents and conditions: (a) Ph2SO, TTBP, CH...
Figure 2: Retrosynthetic analysis of pentasaccharide 48.
Scheme 11: Effects of anomeric leaving groups on glycosylation outcomes. Reagents and conditions: (a) Ph2SO, Tf...
Scheme 12: Reactivity-based one-pot chemoselective glycosylation.
Scheme 13: Preactivation-based iterative glycosylation of thioglycosides.
Scheme 14: BSP/Tf2O promoted synthesis of 75.
Scheme 15: Proposed mechanism for preactivation-based glycosylation strategy.
Figure 3: The preactivations of glycosyl donors 83, 85 and 87 were investigated by low temperature NMR, which...
Scheme 16: The more electron-rich glycosyl donor 91 gave a higher glycosylation yield than the glycosyl donor ...
Scheme 17: Comparison of the BSP/Tf2O and p-TolSCl/AgOTf promoter systems in facilitating the preactivation-ba...
Scheme 18: One-pot synthesis of Globo-H hexasaccharide 105 using building blocks 101, 102, 103 and 104.
Scheme 19: Synthesis of (a) oligosaccharides 109–113 towards (b) 30-mer galactan 115. Reagents and conditions:...
Figure 4: Structure of mycobacterial arabinogalactan 116.
Figure 5: Representative complex glycans from glycolipid family synthesized by the preactivation-based thiogl...
Figure 6: Representative microbial and mammalian oligosaccharides synthesized by the preactivation-based thio...
Figure 7: Some representative mammalian oligosaccharides synthesized by the preactivation-based thioglycoside...
Figure 8: Preparation of a heparan sulfate oligosaccharides library.
Scheme 20: Synthesis of oligo-glucosamines through electrochemical promoted preactivation-based thioglycoside ...
Scheme 21: Synthesis of 2-deoxyglucosides through preactivation. Reagents and conditions: a) AgOTf, p-TolSCl, ...
Scheme 22: Synthesis of tetrasaccharide 153. Reagents and conditions: (a) AgOTf, p-TolSCl, CH2Cl2, −78 °C; the...
Scheme 23: Aglycon transfer from a thioglycosyl acceptor to an activated donor can occur during preactivation-...
Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems
- Marco Mottinelli,
- Mathew P. Leese and
- Barry V. L. Potter
Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182
- electrophilic aromatic substitution that is strongly impacted by the effects of the substituents on the electron density of the aromatic ring in intermediate 4. Given our established interest in exploring structural mimetics for the steroid nucleus we were drawn to explore whether the PFB reaction could be used
- to access libraries of regioisomeric N-aryl-1,2,3,4-tetrahydroisoquinoline derivatives that might facilitate the design of new structural templates for steroid-binding receptors. We thus evaluated the robustness and flexibility of this approach to the THIQ system and considered, in particular, the
Graphical Abstract
Figure 1: Non-steroidal templates from estradiol.
Scheme 1: Pomeranz–Fritsch and Pomeranz–Fritsch–Bobbitt reactions. Conditions: (a) conc. H2SO4; (b) benzene, ...
Scheme 2: Designed synthesis of THIQ. Conditions: (a) NaBH(OAc)3, CHCl3, rt; (b) 6 M HCl or 70% HClO4 (see Table 1),...
Scheme 3: Side reaction during the double alkylation of 7 and possible reaction mechanism for the formation o...
Scheme 4: Competition between the formation of 5- and 7-substituted THIQs. Conditions: (a) 6 M HCl, rt.
Scheme 5: Formation of the 4-hydroxy and 4-methoxy-THIQs. Conditions: (a) 6 M HCl or 70% HClO4, rt (see Table 3).
Scheme 6: Competition between the formation of THIQs 10a,o,p and indoles 16a,o,p. Conditions: (a) 70% HClO4, ...
Scheme 7: Competition between 6- and 7-membered ring formation. Conditions: (a) NaBH(OAc)3, CHCl3, rt; (b) 2,...
Scheme 8: Competition between ring formation para- or meta- to an activating group. Conditions: (a) NaBH(OAc)3...
Strategies toward protecting group-free glycosylation through selective activation of the anomeric center
- A. Michael Downey and
- Michal Hocek
Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123
- worked well with not only simple aliphatic and phenolic alcohols but also with amino acids and steroid alcohols (Figure 1). The authors posit that the stereoselectivity can be rationalized by an oxycarbenium/BF3-coordinated 3-bromo-2-pyridyloxy ion-pair intermediate that is displaced by the alcohol in an
Graphical Abstract
Scheme 1: Solution-state conformations of D-glucose.
Scheme 2: Enzymatic synthesis of oligosaccharides.
Scheme 3: Enzymatic synthesis of a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-termina...
Scheme 4: A) Selected GTs-mediated syntheses of oligosaccharides and other biologically active glycosides. B)...
Scheme 5: Enzymatic synthesis of nucleosides.
Scheme 6: Fischer glycosylation strategies.
Scheme 7: The basis of remote activation (adapted from [37]).
Scheme 8: Classic remote activation employing a MOP donor to access α-anomeric alcohols, carboxylates, and ph...
Figure 1: Synthesis of monoprotected glycosides from a (3-bromo-2-pyridyloxy) β-D-glycopyranosyl donor under ...
Scheme 9: Plausible mechanism for the synthesis of α-galactosides. TBDPS = tert-butyldiphenylsilyl.
Scheme 10: Synthesis of the 6-O-monoprotected galactopyranoside donor for remote activation.
Scheme 11: UDP-galactopyranose mutase-catalyzed isomerization of UDP-Galp to UDP-Galf.
Scheme 12: Synthesis of the 1-thioimidoyl galactofuranosyl donor.
Scheme 13: Glycosylation of MeOH using a self-activating donor in the absence of an external activator. a) Syn...
Scheme 14: The classical Lewis acid-catalyzed glycosylation.
Figure 2: Unprotected glycosyl donors used for the Lewis acid-catalyzed protecting group-free glycosylation r...
Scheme 15: Four-step synthesis of the phenyl β-galactothiopyranosyl donor.
Scheme 16: Protecting-group-free C3′-regioselective glycosylation of sucrose with α–F Glc.
Scheme 17: Synthesis of the α-fluoroglucosyl donor.
Figure 3: Protecting-group-free glycosyl donors and acceptors used in the Au(III)-catalyzed glycosylation.
Scheme 18: Synthesis of the mannosyl donor used in the study [62].
Scheme 19: The Pd-catalyzed stereoretentive glycosylation of arenes using anomeric stannane donors.
Scheme 20: Preparation of the protecting-group-free α and β-stannanes from advanced intermediates for stereoch...
Figure 4: Selective anomeric activating agents providing donors for direct activation of the anomeric carbon.
Scheme 21: One-step access to sugar oxazolines or 1,6-anhydrosugars.
Scheme 22: Enzymatic synthesis of a chitoheptaose using a mutant chitinase.
Scheme 23: One-pot access to glycosyl azides [73], dithiocarbamates [74], and aryl thiols using DMC activation and sub...
Scheme 24: Plausible reaction mechanism.
Scheme 25: Protecting-group-free synthesis of anomeric thiols from unprotected 2-deoxy-2-N-acetyl sugars.
Scheme 26: Protein conjugation of TTL221-PentK with a hyaluronan hexasaccharide thiol.
Scheme 27: Proposed mechanism.
Scheme 28: Direct two-step one-pot access to glycoconjugates through the in situ formation of the glycosyl azi...
Scheme 29: DMC as a phosphate-activating moiety for the synthesis of diphosphates. aβ-1,4-galactose transferas...
Figure 5: Triazinylmorpholinium salts as selective anomeric activating agents.
Scheme 30: One-step synthesis of DBT glycosides from unprotected sugars in aqueous medium.
Scheme 31: Postulated mechanism for the stereoselective formation of α-glycosides.
Scheme 32: DMT-donor synthesis used for metal-catalyzed glycosylation of simple alcohols.
Figure 6: Protecting group-free synthesis of glycosyl sulfonohydrazides (GSH).
Figure 7: The use of GSHs to access 1-O-phosphoryl and alkyl glycosides. A) Glycosylation of aliphatic alcoho...
Scheme 33: A) Proposed mechanism of glycosylation. B) Proposed mechanism for stereoselective azidation of the ...
Scheme 34: Mounting GlcNAc onto a sepharose solid support through a GSH donor.
Scheme 35: Lawesson’s reagent for the formation of 1,2-trans glycosides.
Scheme 36: Protecting-group-free protein conjugation via an in situ-formed thiol glycoside [98].
Scheme 37: pH-Specific glycosylation to functionalize SAMs on gold.
Figure 8: Protecting-group-free availability of phenolic glycosides under Mitsunobu conditions. DEAD = diethy...
Scheme 38: Accessing hydroxyazobenzenes under Mitsunobu conditions for the study of photoswitchable labels. DE...
Scheme 39: Stereoselective protecting-group-free glycosylation of D-glucose to provide the β-glucosyl benzoic ...
Figure 9: Direct synthesis of pyranosyl nucleosides from unactivated and unprotected ribose using optimized M...
Figure 10: Direct synthesis of furanosyl nucleosides from 5-O-monoprotected ribose in a one-pot glycosylation–...
Figure 11: Synthesis of ribofuranosides using a monoprotected ribosyl donor via an anhydrose intermediate.
Figure 12: C5′-modified nucleosides available under our conditions.
Scheme 40: Plausible reaction mechanism for the formation of the anhydrose.
Figure 13: Direct glycosylation of several aliphatic alcohols using catalytic Ti(Ot-Bu)4 in the presence of D-...
Figure 14: Access to glycosides using catalytic PPh3 and CBr4.
Figure 15: Access to ribofuranosyl glycosides as the major product under catalytic conditions. aLiOCl4 (2.0 eq...
Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands
- Nikolay V. Lukashev,
- Gennadii A. Grabovyi,
- Dmitry A. Erzunov,
- Alexey V. Kazantsev,
- Gennadij V. Latyshev,
- Alexei D. Averin and
- Irina P. Beletskaya.
Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55
- arylaminocholanes and cholane-diaminoanthraquinone derivatives by Pd- and Cu-catalyzed amination. Such compounds not only have cation binding properties, but also might be easily introduced in lipid membranes to form ion channels. Appropriate close location of lipophilic steroid fragments in bis(cholanediamino
Graphical Abstract
Figure 1: A tripodal molecular pocket (a) [12] or jellyfish resembling receptors (b) [11,16].
Scheme 1: Example of Pd-catalyzed amination for modification of bile acid derivatives.
Scheme 2: Synthesis of 24-aminocholanols.
Scheme 3: Synthesis of 24-arylaminocholanols by Cu-catalyzed amination.
Scheme 4: Synthesis of 24-arylaminocholanols by Pd-catalyzed amination.
Figure 2: UV–vis spectra of 5c (50 μM solution in MeCN) before and after the addition of 5 equiv of metal per...
Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)
- Alexander Bogdanov,
- Cora Hertzer,
- Stefan Kehraus,
- Samuel Nietzer,
- Sven Rohde,
- Peter J. Schupp,
- Heike Wägele and
- Gabriele M. König
Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50
- peak with a retention time of 14.7 min of the UPLC-chromatogram of VLC fraction 7, is characteristic for the secosteroid 1 or the polyhydroxylated steroid 4, both with a molecular weight of 492 Da. More importantly, UPLC–HRMS investigations produced also some peaks with m/z values that cannot be linked
- to isolated compounds 1–19. Thus, in VLC fraction 7 and 8 an m/z value of 287.24 (M + H) indicates most probably the presence of the instable sarcophytonin A with a molecular weight of 286.23 Da [16]. VLC fractions 7 and 8 also contain m/z values characteristic for steroid constituents of Sarcophyton
- soft corals that could not be isolated in the current study, e.g., m/z 397.35 (M + H) suggests the presence of a steroid compound reported by Kobayashi et al. from Sarcophyton glaucum [17] with a molecular mass of 396 Da as outlined in Table S7B (Supporting Information File 1). Detailed analysis of the
Graphical Abstract
Figure 1: Secondary metabolites isolated in this study from P. longicirrum.
Figure 2: Structures of secondary metabolites from P. longicirrum as described by Coll et al. in 1985 [13].
Figure 3: Significant 1H,1H COSY correlations as found in compound 1.
Figure 4: Secosterols [22,24] related to 3β,5α,6β-trihydroxy-9-oxo-9,11-secogorgostan-11-ol (1) from P. longicirrum.
Figure 5: Conformational structure of 1 (key NOESY correlations are indicated with blue arrows; coupling cons...
Figure 6: Structure of cembranoid 5. 1H,1H spin systems (A, B and C) are indicated in bold, arrows show key H...
Figure 7: Compound 5 and the most closely related cembranoids from soft corals.
Figure 8: Proposed configuration and selected NOE correlations of bisepoxide 12 (key NOE correlations are ind...
Figure 9: Structures of bisglaucumlids A–C (23–25).
Figure 10: Proposed configuration of the eastern part (rings B, C and D) of isobisglaucumlides B and C (14 and ...
Figure 11: Effect of Phyllodesmium metabolites in different concentrations on predation by Canthigaster soland...
Figure 12: Phylogenetic tree of octocorals relevant as putative food sources for Phyllodesmium spp. Phylogram ...
Synthesis of 1-indanones with a broad range of biological activity
- Marika Turek,
- Dorota Szczęsna,
- Marek Koprowski and
- Piotr Bałczewski
Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48
- derivative 265 having the steroid framework from 1,2-dihydro-7-methoxy-4-vinylnaphthalene (262) and α-bromo substituted cyclopentenone 263 by the SnCl4-catalyzed Diels–Alder cycloaddition [102]. In this reaction, 1-indanone 265 was obtained in 59% yield via dehydrogenation of a mixture of cycloadducts 264a–c
Graphical Abstract
Figure 1: Biologically active 1-indanones and their structural analogues.
Figure 2: Number of papers about (a) 1-indanones, (b) synthesis of 1-indanones.
Scheme 1: Synthesis of 1-indanone (2) from hydrocinnamic acid (1).
Scheme 2: Synthesis of 1-indanone (2) from 3-(2-bromophenyl)propionic acid (3).
Scheme 3: Synthesis of 1-indanones 5 from 3-arylpropionic acids 4.
Scheme 4: Synthesis of kinamycin (9a) and methylkinamycin C (9b).
Scheme 5: Synthesis of trifluoromethyl-substituted arylpropionic acids 12, 1-indanones 13 and dihydrocoumarin...
Scheme 6: Synthesis of 1-indanones 16 from benzoic acids 15.
Scheme 7: Synthesis of 1-indanones 18 from arylpropionic and 3-arylacrylic acids 17.
Scheme 8: The NbCl5-induced one-step synthesis of 1-indanones 22.
Scheme 9: Synthesis of biologically active 1-indanone derivatives 26.
Scheme 10: Synthesis of enantiomerically pure indatraline ((−)-29).
Scheme 11: Synthesis of 1-indanone (2) from the acyl chloride 30.
Scheme 12: Synthesis of the mechanism-based inhibitors 33 of coelenterazine.
Scheme 13: Synthesis of the indane 2-imidazole derivative 37.
Scheme 14: Synthesis of fluorinated PAHs 41.
Scheme 15: Synthesis of 1-indanones 43 via transition metal complexes-catalyzed carbonylative cyclization of m...
Scheme 16: Synthesis of 6-methyl-1-indanone (46).
Scheme 17: Synthesis of 1-indanone (2) from ester 48.
Scheme 18: Synthesis of benzopyronaphthoquinone 51 from the spiro-1-indanone 50.
Scheme 19: Synthesis of the selective endothelin A receptor antagonist 55.
Scheme 20: Synthesis of 1-indanones 60 from methyl vinyl ketone (57).
Scheme 21: Synthesis of 1-indanones 64 from diethyl phthalate 61.
Scheme 22: Synthesis of 1-indanone derivatives 66 from various Meldrum’s acids 65.
Scheme 23: Synthesis of halo 1-indanones 69.
Scheme 24: Synthesis of substituted 1-indanones 71.
Scheme 25: Synthesis of spiro- and fused 1-indanones 73 and 74.
Scheme 26: Synthesis of spiro-1,3-indanodiones 77.
Scheme 27: Mechanistic pathway for the NHC-catalyzed Stetter–Aldol–Michael reaction.
Scheme 28: Synthesis of 2-benzylidene-1-indanone derivatives 88a–d.
Scheme 29: Synthesis of 1-indanone derivatives 90a–i.
Scheme 30: Synthesis of 1-indanones 96 from o-bromobenzaldehydes 93 and alkynes 94.
Scheme 31: Synthesis of 3-hydroxy-1-indanones 99.
Scheme 32: Photochemical preparation of 1-indanones 103 from ketones 100.
Scheme 33: Synthesis of chiral 3-aryl-1-indanones 107.
Scheme 34: Photochemical isomerization of 2-methylbenzil 108.
Scheme 35: Synthesis of 2-hydroxy-1-indanones 111a–c.
Scheme 36: Synthesis of 1-indanone derivatives 113 and 114 from η6-1,2-dioxobenzocyclobutene complex 112.
Scheme 37: Synthesis of nakiterpiosin (117).
Scheme 38: Synthesis of 2-alkyl-1-indanones 120.
Scheme 39: Synthesis of fluorine-containing 1-indanone derivatives 123.
Scheme 40: Synthesis of 2-benzylidene and 2-benzyl-1-indanones 126, 127 from the chalcone 124.
Scheme 41: Synthesis of 2-bromo-6-methoxy-3-phenyl-1-indanone (130).
Scheme 42: Synthesis of combretastatin A-4-like indanones 132a–s.
Figure 3: Chemical structures of investigated dienones 133 and synthesized cyclic products 134–137.
Figure 4: Chemical structures of 1-indanones and their heteroatom analogues 138–142.
Scheme 43: Synthesis of 2-phosphorylated and 2-non-phosphorylated 1-indanones 147 and 148 from β-ketophosphona...
Scheme 44: Photochemical synthesis of 1-indanone derivatives 150, 153a, 153b.
Scheme 45: Synthesis of polysubstituted-1-indanones 155, 157.
Scheme 46: Synthesis of 1-indanones 159a–g from α-arylpropargyl alcohols 158 using RhCl(PPh3)3 as a catalyst.
Scheme 47: Synthesis of optically active 1-indanones 162 via the asymmetric Rh-catalyzed isomerization of race...
Scheme 48: Mechanism of the Rh-catalyzed isomerization of α-arylpropargyl alcohols 161 to 1-indanones 162.
Figure 5: Chemical structure of abicoviromycin (168) and its new benzo derivative 169.
Scheme 49: Synthesis of racemic benzoabicoviromycin 172.
Scheme 50: Synthesis of [14C]indene 176.
Scheme 51: Synthesis of indanone derivatives 178–180.
Scheme 52: Synthesis of racemic pterosin A 186.
Scheme 53: Synthesis of trans-2,3-disubstituted 1-indanones 189.
Scheme 54: Synthesis of 3-aryl-1-indanone derivatives 192.
Scheme 55: Synthesis of 1-indanone derivatives 194 from 3-(2-iodoaryl)propanonitriles 193.
Scheme 56: Synthesis of 1-indanones 200–204 by cyclization of aromatic nitriles.
Scheme 57: Synthesis of 1,1’-spirobi[indan-3,3’-dione] derivative 208.
Scheme 58: Total synthesis of atipamezole analogues 211.
Scheme 59: Synthesis of 3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1’-indan]-5,5’-diol hydrochloride 216.
Scheme 60: Synthesis of 3-arylindan-1-ones 219.
Scheme 61: Synthesis of 2-hydroxy-1-indanones 222.
Scheme 62: Synthesis of the 1-indanone 224 from the THP/MOM protected chalcone epoxide 223.
Scheme 63: Synthesis of 1-indanones 227 from γ,δ-epoxy ketones 226.
Scheme 64: Synthesis of 2-hydroxy-2-methylindanone (230).
Scheme 65: Synthesis of 1-indanone derivatives 234 from cyclopropanol derivatives 233.
Scheme 66: Synthesis of substituted 1-indanone derivatives 237.
Scheme 67: Synthesis of 7-methyl substituted 1-indanone 241 from 1,3-pentadiene (238) and 2-cyclopentenone (239...
Scheme 68: Synthesis of disubstituted 1-indanone 246 from the siloxydiene 244 and 2-cyclopentenone 239.
Scheme 69: Synthesis of 5-hydroxy-1-indanone (250) via the Diels–Alder reaction of 1,3-diene 248 with sulfoxid...
Scheme 70: Synthesis of halogenated 1-indanones 253a and 253b.
Scheme 71: Synthesis of 1-indanones 257 and 258 from 2-bromocyclopentenones 254.
Scheme 72: Synthesis of 1-indanone 261 from 2-bromo-4-acetoxy-2-cyclopenten-1-one (260) and 1,2-dihydro-4-viny...
Scheme 73: Synthesis of 1-indanone 265 from 1,2-dihydro-7-methoxy-4-vinylnaphthalene (262) and bromo-substitut...
Scheme 74: Synthesis of 1-indanone 268 from dihydro-3-vinylphenanthrene 266 and 4-acetoxy-2-cyclopenten-1-one (...
Scheme 75: Synthesis of 1-indanone 271 from phenylselenyl-substituted cyclopentenone 268.
Scheme 76: Synthesis of 1-indanone 272 from the trienone 270.
Scheme 77: Synthesis of the 1-indanone 276 from the aldehyde 273.
Scheme 78: Synthesis of 1-indanones 278 and 279.
Scheme 79: Synthesis of 1-indanone 285 from octa-1,7-diyne (282) and cyclopentenone 239.
Scheme 80: Synthesis of benz[f]indan-1-one (287) from cyclopentenone 239 and o-bis(dibromomethyl)benzene (286)....
Scheme 81: Synthesis of 3-methyl-substituted benz[f]indan-1-one 291 from o-bis(dibromomethyl)benzene (286) and...
Scheme 82: Synthesis of benz[f]indan-1-one (295) from the anthracene epidioxide 292.
Scheme 83: Synthesis of 1-indanone 299 from homophthalic anhydride 298 and cyclopentynone 297.
Scheme 84: Synthesis of cyano-substituted 1-indanone derivative 301 from 2-cyanomethylbenzaldehyde (300) and c...
Scheme 85: Synthesis of 1-indanone derivatives 303–305 from ketene dithioacetals 302.
Scheme 86: Synthesis of 1-indanones 309–316.
Scheme 87: Mechanism of the hexadehydro-Diels–Alder (HDDA) reaction.
Scheme 88: Synthesis of 1-indenone 318 and 1-indanones 320 and 321 from tetraynes 317 and 319.
Scheme 89: Synthesis of 1-indanone 320 from the triyn 319.
Scheme 90: Synthesis 1-indanone 328 from 2-methylfuran 324.
Scheme 91: Synthesis of 1-indanones 330 and 331 from furans 329.
Scheme 92: Synthesis of 1-indanone 333 from the cycloadduct 332.
Scheme 93: Synthesis of (S)-3-arylindan-1-ones 335.
Scheme 94: Synthesis of (R)-2-acetoxy-1-indanone 338.
Figure 6: Chemical structures of obtained cyclopenta[α]phenanthrenes 339.
Scheme 95: Synthesis of the benzoindanone 343 from arylacetaldehyde 340 with 1-trimethylsilyloxycyclopentene (...
Rearrangements of organic peroxides and related processes
- Ivan A. Yaremenko,
- Vera A. Vil’,
- Dmitry V. Demchuk and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162
Graphical Abstract
Figure 1: The named transformations considered in this review.
Scheme 1: The Baeyer–Villiger oxidation.
Scheme 2: The general mechanism of the peracid-promoted Baeyer–Villiger oxidation.
Scheme 3: General mechanism of the Lewis acid-catalyzed Baeyer–Villiger rearrangement.
Scheme 4: The theoretically studied mechanism of the BV oxidation reaction promoted by H2O2 and the Lewis aci...
Scheme 5: Proton movements in the transition states of the Baeyer–Villiger oxidation.
Scheme 6: The dependence of the course of the Baeyer–Villiger oxidation on the type of O–O-bond cleavage in t...
Scheme 7: The acid-catalyzed Baeyer–Villiger oxidation of cyclic epoxy ketones 22.
Scheme 8: Oxidation of isophorone oxide 29.
Scheme 9: Synthesis of acyl phosphate 32 from acyl phosphonate 31.
Scheme 10: Synthesis of aflatoxin B2 (36).
Scheme 11: The Baeyer–Villiger rearrangement of ketones 37 to lactones 38.
Scheme 12: Synthesis of 3,4-dimethoxybenzoic acid (40) via Baeyer–Villiger oxidation.
Scheme 13: Oxone transforms α,β-unsaturated ketones 43 into vinyl acetates 44.
Scheme 14: The Baeyer–Villiger oxidation of ketones 45 using diaryl diselenide and hydrogen peroxide.
Scheme 15: Baeyer–Villiger oxidation of (E)-2-methylenecyclobutanones.
Scheme 16: Oxidation of β-ionone (56) by H2O2/(BnSe)2 with formation of (E)-2-(2,6,6-trimethylcyclohex-1-en-1-...
Scheme 17: The mechanism of oxidation of ketones 58a–f by hydrogen peroxide in the presence of arsonated polys...
Scheme 18: Oxidation of ketone (58b) by H2O2 to 6-methylcaprolactone (59b) catalyzed by Pt complex 66·BF4.
Scheme 19: Oxidation of ketones 67 with H2O2 in the presence of [(dppb}Pt(µ-OH)]22+.
Scheme 20: The mechanism of oxidation of ketones 67 in the presence of [(dppb}Pt(µ-OH)]22+ and H2O2.
Scheme 21: Oxidation of benzaldehydes 69 in the presence of the H2O2/MeReO3 system.
Scheme 22: Oxidation of acetophenones 72 in the presence of the H2O2/MeReO3 system.
Scheme 23: Baeyer–Villiger oxidation of 2-adamantanone (45c) in the presence of Sn-containing mesoporous silic...
Scheme 24: Aerobic Baeyer–Villiger oxidation of ketones 76 using metal-free carbon.
Scheme 25: A regioselective Baeyer-Villiger oxidation of functionalized cyclohexenones 78 into a dihydrooxepin...
Scheme 26: The oxidation of aldehydes and ketones 80 by H2O2 catalyzed by Co4HP2Mo15V3O62.
Scheme 27: The cleavage of ketones 82 with hydrogen peroxide in alkaline solution.
Scheme 28: Oxidation of ketones 85 to esters 86 with H2O2–urea in the presence of KHCO3.
Scheme 29: Mechanism of the asymmetric oxidation of cyclopentane-1,2-dione 87a with the Ti(OiPr)4/(+)DET/t-BuO...
Scheme 30: The oxidation of cis-4-tert-butyl-2-fluorocyclohexanone (93) with m-chloroperbenzoic acid.
Scheme 31: The mechanism of the asymmetric oxidation of 3-substituted cyclobutanone 96a in the presence of chi...
Scheme 32: Enantioselective Baeyer–Villiger oxidation of cyclic ketones 98.
Scheme 33: Regio- and enantioselective Baeyer–Villiger oxidation of cyclic ketones 101.
Scheme 34: The proposed mechanism of the Baeyer–Villiger oxidation of acetal 105f.
Scheme 35: Synthesis of hydroxy-10H-acridin-9-one 117 from tetramethoxyanthracene 114.
Scheme 36: The Baeyer–Villiger oxidation of the fully substituted pyrrole 120.
Scheme 37: The Criegee rearrangement.
Scheme 38: The mechanism of the Criegee reaction of a peracid with a tertiary alcohol 122.
Scheme 39: Criegee rearrangement of decaline ethylperoxoate 127 into ketal 128.
Scheme 40: The ionic cleavage of 2-methoxy-2-propyl perester 129.
Scheme 41: The Criegee rearrangement of α-methoxy hydroperoxide 136.
Scheme 42: Synthesis of enol esters and acetals via the Criegee rearrangement.
Scheme 43: Proposed mechanism of the transformation of 1-hydroperoxy-2-oxabicycloalkanones 147a–d.
Scheme 44: Transformation of 3-hydroxy-1,2-dioxolanes 151 into diketone derivatives 152.
Scheme 45: Criegee rearrangement of peroxide 153 with the mono-, di-, and tri-O-insertion.
Scheme 46: The sequential Criegee rearrangements of adamantanes 157a,b.
Scheme 47: Synthesis of diaryl carbonates 160a–d from triarylmethanols 159a–d through successive oxygen insert...
Scheme 48: The synthesis of sesquiterpenes 162 from ketone 161 with a Criegee rearrangement as one key step.
Scheme 49: Synthesis of trans-hydrindan derivatives 164, 165.
Scheme 50: The Hock rearrangement.
Scheme 51: The general scheme of the cumene process.
Scheme 52: The Hock rearrangement of aliphatic hydroperoxides.
Scheme 53: The mechanism of solvolysis of brosylates 174a–c and spiro cyclopropyl carbinols 175a–c in THF/H2O2....
Scheme 54: The fragmentation mechanism of hydroperoxy acetals 178 to esters 179.
Scheme 55: The acid-catalyzed rearrangement of phenylcyclopentyl hydroperoxide 181.
Scheme 56: The peroxidation of tertiary alcohols in the presence of a catalytic amount of acid.
Scheme 57: The acid-catalyzed reaction of bicyclic secondary alcohols 192 with hydrogen peroxide.
Scheme 58: The photooxidation of 5,6-disubstituted 3,4-dihydro-2H-pyrans 196.
Scheme 59: The oxidation of tertiary alcohols 200a–g, 203a,b, and 206.
Scheme 60: Transformation of functional peroxide 209 leading to 2,3-disubstitued furans 210 in one step.
Scheme 61: The synthesis of carbazoles 213 via peroxide rearrangement.
Scheme 62: The construction of C–N bonds using the Hock rearrangement.
Scheme 63: The synthesis of moiety 218 from 217 which is a structural motif in the antitumor–antibiotic of CC-...
Scheme 64: The in vivo oxidation steps of cholesterol (219) by singlet oxygen.
Scheme 65: The proposed mechanism of the rearrangement of cholesterol-5α-OOH 220.
Scheme 66: Photochemical route to artemisinin via Hock rearrangement of 223.
Scheme 67: The Kornblum–DeLaMare rearrangement.
Scheme 68: Kornblum–DeLaMare transformation of 1-phenylethyl tert-butyl peroxide (225).
Scheme 69: The synthesis 4-hydroxyenones 230 from peroxide 229.
Scheme 70: The Kornblum–DeLaMare rearrangement of peroxide 232.
Scheme 71: The reduction of peroxide 234.
Scheme 72: The Kornblum–DeLaMare rearrangement of endoperoxide 236.
Scheme 73: The rearrangement of peroxide 238 under Kornblum–DeLaMare conditions.
Scheme 74: The proposed mechanism of rearrangement of peroxide 238.
Scheme 75: The Kornblum–DeLaMare rearrangement of peroxides 242a,b.
Scheme 76: The base-catalyzed rearrangements of bicyclic endoperoxides having electron-withdrawing substituent...
Scheme 77: The base-catalyzed rearrangements of bicyclic endoperoxides 249a,b having electron-donating substit...
Scheme 78: The base-catalyzed rearrangements of bridge-head substituted bicyclic endoperoxides 251a,b.
Scheme 79: The Kornblum–DeLaMare rearrangement of hydroperoxide 253.
Scheme 80: Synthesis of β-hydroxy hydroperoxide 254 from endoperoxide 253.
Scheme 81: The amine-catalyzed rearrangement of bicyclic endoperoxide 263.
Scheme 82: The base-catalyzed rearrangement of meso-endoperoxide 268 into 269.
Scheme 83: The photooxidation of 271 and subsequent Kornblum–DeLaMare reaction.
Scheme 84: The Kornblum–DeLaMare rearrangement as one step in the oxidation reaction of enamines.
Scheme 85: The Kornblum–DeLaMare rearrangement of 3,5-dihydro-1,2-dioxenes 284, 1,2-dioxanes 286, and tert-but...
Scheme 86: The Kornblum–DeLaMare rearrangement of epoxy dioxanes 290a–d.
Scheme 87: Rearrangement of prostaglandin H2 292.
Scheme 88: The synthesis of epicoccin G (297).
Scheme 89: The Kornblum–DeLaMare rearrangement used in the synthesis of phomactin A.
Scheme 90: The Kornblum–DeLaMare rearrangement in the synthesis of 3H-quinazolin-4-one 303.
Scheme 91: The Kornblum–DeLaMare rearrangement in the synthesis of dolabriferol (308).
Scheme 92: Sequential transformation of 3-substituted 2-pyridones 309 into 3-hydroxypyridine-2,6-diones 311 in...
Scheme 93: The Kornblum–DeLaMare rearrangement of peroxide 312 into hydroxy enone 313.
Scheme 94: The Kornblum–DeLaMare rearrangement in the synthesis of polyfunctionalized carbonyl compounds 317.
Scheme 95: The Kornblum–DeLaMare rearrangement in the synthesis of (Z)-β-perfluoroalkylenaminones 320.
Scheme 96: The Kornblum–DeLaMare rearrangement in the synthesis of γ-ketoester 322.
Scheme 97: The Kornblum–DeLaMare rearrangement in the synthesis of diterpenoids 326 and 328.
Scheme 98: The synthesis of natural products hainanolidol (331) and harringtonolide (332) from peroxide 329.
Scheme 99: The synthesis of trans-fused butyrolactones 339 and 340.
Scheme 100: The synthesis of leucosceptroid C (343) and leucosceptroid P (344) via the Kornblum–DeLaMare rearra...
Scheme 101: The Dakin oxidation of arylaldehydes or acetophenones.
Scheme 102: The mechanism of the Dakin oxidation.
Scheme 103: A solvent-free Dakin reaction of aromatic aldehydes 356.
Scheme 104: The organocatalytic Dakin oxidation of electron-rich arylaldehydes 358.
Scheme 105: The Dakin oxidation of electron-rich arylaldehydes 361.
Scheme 106: The Dakin oxidation of arylaldehydes 358 in water extract of banana (WEB).
Scheme 107: A one-pot approach towards indolo[2,1-b]quinazolines 364 from indole-3-carbaldehydes 363 through th...
Scheme 108: The synthesis of phenols 367a–c from benzaldehydes 366a-c via acid-catalyzed Dakin oxidation.
Scheme 109: Possible transformation paths of the highly polarized boric acid coordinated H2O2–aldehyde adduct 3...
Scheme 110: The Elbs oxidation of phenols 375 to hydroquinones.
Scheme 111: The mechanism of the Elbs persulfate oxidation of phenols 375 affording p-hydroquinones 376.
Scheme 112: Oxidation of 2-pyridones 380 under Elbs persulfate oxidation conditions.
Scheme 113: Synthesis of 3-hydroxy-4-pyridone (384) via an Elbs oxidation of 4-pyridone (382).
Scheme 114: The Schenck rearrangement.
Scheme 115: The Smith rearrangement.
Scheme 116: Three main pathways of the Schenck rearrangement.
Scheme 117: The isomerization of hydroperoxides 388 and 389.
Scheme 118: Trapping of dioxacyclopentyl radical 392 by oxygen.
Scheme 119: The hypothetical mechanism of the Schenck rearrangement of peroxide 394.
Scheme 120: The autoxidation of oleic acid (397) with the use of labeled isotope 18O2.
Scheme 121: The rearrangement of 18O-labeled hydroperoxide 400 under an atmosphere of 16O2.
Scheme 122: The rearrangement of the oleate-derived allylic hydroperoxides (S)-421 and (R)-425.
Scheme 123: Mechanisms of Schenck and Smith rearrangements.
Scheme 124: The rearrangement and cyclization of 433.
Scheme 125: The Wieland rearrangement.
Scheme 126: The rearrangement of bis(triphenylsilyl) 439 or bis(triphenylgermyl) 441 peroxides.
Scheme 127: The oxidative transformation of cyclic ketones.
Scheme 128: The hydroxylation of cyclohexene (447) in the presence of tungstic acid.
Scheme 129: The oxidation of cyclohexene (447) under the action of hydrogen peroxide.
Scheme 130: The reaction of butenylacetylacetone 455 with hydrogen peroxide.
Scheme 131: The oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 132: The proposed mechanism for the oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 133: The rearrangement of ozonides.
Scheme 134: The acid-catalyzed oxidative rearrangement of malondialdehydes 462 under the action of H2O2.
Scheme 135: Pathways of the Lewis acid-catalyzed cleavage of dialkyl peroxides 465 and ozonides 466.
Scheme 136: The mechanism of the transformation of (tert-butyldioxy)cyclohexanedienones 472.
Scheme 137: The synthesis of Vitamin K3 from 472a.
Scheme 138: Proposed mechanism for the transformation of 478d into silylated endoperoxide 479d.
Scheme 139: The rearrangement of hydroperoxide 485 to form diketone 486.
Scheme 140: The base-catalyzed rearrangement of cyclic peroxides 488a–g.
Scheme 141: Synthesis of chiral epoxides and aldols from peroxy hemiketals 491.
Scheme 142: The multistep transformation of (R)-carvone (494) to endoperoxides 496a–e.
Scheme 143: The decomposition of anthracene endoperoxide 499.
Scheme 144: Synthesis of esters 503 from aldehydes 501 via rearrangement of peroxides 502.
Scheme 145: Two possible paths for the base-promoted decomposition of α-azidoperoxides 502.
Scheme 146: The Story decomposition of cyclic diperoxide 506a.
Scheme 147: The Story decomposition of cyclic triperoxide 506b.
Scheme 148: The thermal rearrangement of endoperoxides A into diepoxides B.
Scheme 149: The transformation of peroxide 510 in the synthesis of stemolide (511).
Scheme 150: The possible mechanism of the rearrangement of endoperoxide 261g.
Scheme 151: The photooxidation of indene 517.
Scheme 152: The isomerization of ascaridole (523).
Scheme 153: The isomerization of peroxide 525.
Scheme 154: The thermal transformation of endoperoxide 355.
Scheme 155: The photooxidation of cyclopentadiene (529) at a temperature higher than 0 °C.
Scheme 156: The thermal rearrangement of endoperoxides 538a,b.
Scheme 157: The transformation of peroxides 541.
Scheme 158: The thermal rearrangements of strained cyclic peroxides.
Scheme 159: The thermal rearrangement of diacyl peroxide 551 in the synthesis of C4-epi-lomaiviticin B core 553....
Scheme 160: The 1O2 oxidation of tryptophan (554) and rearrangement of dioxetane intermediate 555.
Scheme 161: The Fe(II)-promoted cleavage of aryl-substituted bicyclic peroxides.
Scheme 162: The proposed mechanism of the Fe(II)-promoted rearrangement of 557a–c.
Scheme 163: The reaction of dioxolane 563 with Fe(II) sulfate.
Scheme 164: Fe(II)-promoted rearrangement of 1,2-dioxane 565.
Scheme 165: Fe(II) cysteinate-promoted rearrangement of 1,2-dioxolane 568.
Scheme 166: The transformation of 1,2-dioxanes 572a–c under the action of FeCl2.
Scheme 167: Fe(II) cysteinate-promoted transformation of tetraoxane 574.
Scheme 168: The CoTPP-catalyzed transformation of bicyclic endoperoxides 600a–d.
Scheme 169: The CoTPP-catalyzed transformation of epoxy-1,2-dioxanes.
Scheme 170: The Ru(II)-catalyzed reactions of 1,4-endoperoxide 261g.
Scheme 171: The Ru(II)-catalyzed transformation as a key step in the synthesis of elyiapyrone A (610) from 1,4-...
Scheme 172: Peroxides with antimalarial activity.
Scheme 173: The interaction of iron ions with artemisinin (616).
Scheme 174: The interaction of FeCl2 with 1,2-dioxanes 623, 624.
Scheme 175: The mechanism of reaction 623 and 624 with Fe(II)Cl2.
Scheme 176: The reaction of bicyclic natural endoperoxides G3-factors 631–633 with FeSO4.
Scheme 177: The transformation of terpene cardamom peroxide 639.
Scheme 178: The different ways of the cleavage of tetraoxane 643.
Scheme 179: The LC–MS analysis of interaction of tetraoxane 646 with iron(II)heme 647.
Scheme 180: The rearrangement of 3,6-epidioxy-1,10-bisaboladiene (EDBD, 649).
Scheme 181: Easily oxidized substrates.
Scheme 182: Biopathway of synthesis of prostaglandins.
Scheme 183: The reduction and rearrangements of isoprostanes.
Scheme 184: The partial mechanism for linoleate 658 oxidation.
Scheme 185: The transformation of lipid hydroperoxide.
Scheme 186: The acid-catalyzed cleavage of the product from free-radical oxidation of cholesterol (667).
Scheme 187: Two pathways of catechols oxidation.
Scheme 188: Criegee-like or Hock-like rearrangement of the intermediate hydroperoxide 675 in dioxygenase enzyme...
Scheme 189: Carotinoides 679 cleavage by carotenoid cleavage dioxygenases.
From steroids to aqueous supramolecular chemistry: an autobiographical career review
- Bruce C. Gibb
Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69
- , “slab of hydrocarbon”. Hence this example of selective, remote functionalization of the steroid framework was captivating. This captivation was itself pivotal to my career path, and it is a constant reminder to me (and hopefully young practitioners I’ve told this story to) how important it is to keep
- more specifically, the subset of this class of enzymes that play an important role in steroidogenesis. How does the body synthesize all those steroid hormones? How does Nature carry out remote functionalization on these slabs of hydrocarbon? The answer of course involves a heme-cofactor and an
- exceedingly stable capsular complexes (Figure 6). Regarding their stability, even at 5 μM, NMR showed complete encapsulation of estradiol; giving a minimum apparent binding constant for the empty capsule (the host is actually monomeric in the absence of guests) of 1 × 108 M−1. When the steroid was very large
Graphical Abstract
Scheme 1: The formation of a 1:1 complex and a 2:1 supramolecular nano-capsule complex from bowl-shaped “cavi...
Scheme 2: Abbreviated synthesis of 7-amino-2-phenyl-6-azaindolizine.
Figure 1: My two favorite compounds for my Ph.D. dissertation, “The Synthesis and Structural Examination of 3...
Scheme 3: An inspiring chlorination from the group of Ronald Breslow.
Scheme 4: The carceplex reaction.
Figure 2: Schematic of a cavitein.
Figure 3: General structure of zinc-TPA complexes.
Scheme 5: Stereoselective bridging of a resorcinarene with benzal halides.
Scheme 6: An eight-fold Ullman ether “weaving” reaction.
Scheme 7: Directed ortho-metallation of the deep-cavity cavitands, showing the mono-endo substituted to tetra-...
Scheme 8: Macrocycle synthesis via resorcinarene covalent templates.
Figure 4: Tris-pyridyl hosts.
Figure 5: (Center) Chemical structure of the octa-acid host. (Left and right) Respective space-filling repres...
Figure 6: Cartoons of the 2:1 host–guest complexes of estradiol (left) and cholesterol (right).
Figure 7: Representative guests for the capsular complexes formed by octa-acid (stoichiometry shown in parent...
Figure 8: A dendrimer-coated cavitand.
Figure 9: Selective oxidation of olefins by singlet oxygen.
Figure 10: a) Preferred packing motifs of methyl, pentyl and octyl guests. b) Product distribution observed fo...
Figure 11: Schematic of the competition of two esters for the capsule formed by octa-acid. The ester that bind...
Figure 12: Schematic of the inter-phase separation of propane and butane; the latter binds more strongly to th...
Figure 13: Structure of tetra-endo-methyl octa-acid (TEMOA).
Figure 14: Assembly properties of TEMOA.
Figure 15: How salts influence the association constant (Ka) for the binding of ClO4– to octa-acid (Figure 4). The ind...
Biosynthesis of α-pyrones
- Till F. Schäberle
Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56
- are an important group of steroids containing an α-pyrone moiety. The α-pyrone ring is here connected to a steroid nucleus, as exemplified in bufalin (31, Figure 7). These α-pyrones were detected in several plants, as well as in animals. The vast amount of derivatives shows also very diverse
Graphical Abstract
Figure 1: Selected monocyclic and monobenzo α-pyrone structures.
Figure 2: The basic core structure of dibenzo-α-pyrones.
Figure 3: Selected dibenzo-α-pyrones.
Figure 4: Structure of ellagic acid and of the urolithins, the latter metabolized from ellagic acid by intest...
Figure 5: Structure of murayalactone, the only dibenzo-α-pyrone described from bacteria.
Figure 6: Structures of the 6-pentyl-2-pyrone (29) and of trichopyrone (30). Only 29 showed antifungal activi...
Figure 7: Selected monocyclic α-pyrones.
Figure 8: Structures of the gibepyrones A–F.
Figure 9: Structures of the phomenins A and B.
Figure 10: Structures of monocyclic α-pyrones showing pheromone (47) and antitumor activity (48), respectively....
Figure 11: Structures of 6-alkyl (alkoxy or alkylthio)-4-aryl-3-(4-methanesulfonylphenyl)pyrones.
Figure 12: Structures of kavalactones.
Figure 13: Strutures of germicins.
Figure 14: Structures of the pseudopyronines.
Figure 15: The structures of the monobenzo-α-pyrone anticoagulant drugs warfarin and phenprocoumon.
Figure 16: Structures of selected monobenzo-α-pyrones.
Figure 17: Hypothetical pathway of 29 generation from linoleic acid [34].
Figure 18: Proposed biosynthetic pathway of alternariol (modified from [77]). Malonyl-CoA building blocks are appl...
Figure 19: Structures of phenylnannolones and of enterocin, both biosynthesized via polyketide synthase system...
Figure 20: Pyrone ring formation. Examples for the three types of PKS systems are shown in A–C. In D the mecha...
Figure 21: Structures of csypyrones.
Figure 22: Schematic drawing of the T-shaped catalytic cavities of the related enzymes CorB and MxnB. The two ...
Figure 23: Stereo representation of the CorB binding situation (modified from [89]). The substrate mimic (dark vio...
Figure 24: Proposed mechanism for the CsyB enzymatic reaction. A) Coupling reaction of the β-keto fatty acyl i...
Figure 25: Proposed biosynthesis of photopyrone D (37) by the enzyme PpyS from P. luminescens (modified from [63])...
Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction
- Mino R. Caira,
- Susan A. Bourne,
- Halima Samsodien and
- Vincent J. Smith
Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281
- diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion
- structures to be described are the first for crystalline CD inclusion complexes of a representative bioactive steroid and as such, their molecular structures shed some light on the nature of cyclodextrin-steroid interactions, including the phenomenon of ‘mutually induced fit’ accompanying complexation. This
- feature, while commonly observed in protein–ligand recognition and selection, is rare for small molecule structures [1]. In addition to the solid-state results detailed below, we report original data on the use of CDs to enhance the aqeous solubility of 2ME. The title steroid, originally identified as an
Graphical Abstract
Figure 1: Chemical structures of 2-methoxyestradiol (top) and the derivatised CDs DIMEB and TRIMEB (bottom).
Figure 2: The mode of inclusion of 2ME in the DIMEB cavity (a), space-filling side view of the complex with t...
Figure 3: Stereoview of the asymmetric unit in the crystal of the inclusion complex TRIMEB•2ME, with the host...
Figure 4: Space-filling images of complex unit A (as representative of units A and B) (a) and complex unit C ...
Figure 5: Inclination of the mean plane of the included 2ME molecule relative to the O4-heptagon of the host ...
Figure 6: Overlay of the steroid nucleus of 2ME (blue) in its own crystal with the refined models (grey) of t...
Figure 7: The TRIMEB·2ME complex unit D with two distinct (guest)O19-H···O(host) hydrogen bonds highlighted. ...
Figure 8: Dissolution profiles in water at 37 °C for untreated 2ME and various β-CD-containing preparations o...
