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Search for "metabolite" in Full Text gives 160 result(s) in Beilstein Journal of Organic Chemistry.
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
- . Nakiterpiosin (117) is a marine sponge metabolite which demonstrates a potent cytotoxicity against the P388 leukemic cell line. The photo-variant of the Nazarov cyclization has been applied as one of the steps in the total synthesis of nakiterpiosin (117, Scheme 37) [63]. Starting from substrate 115, 1-indanone
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 (...
Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds
- Sophie Letort,
- Michaël Bosco,
- Benedetta Cornelio,
- Frédérique Brégier,
- Sébastien Daulon,
- Géraldine Gouhier and
- François Estour
Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45
- pesticide inclusion into the cyclodextrin cavity undeniably influence the degradation process. Indeed, it was shown that the lowest hydrolysis rates correspond to the highest dissociation constants from TRIMEB [36][37]. As methyl paraoxon represents the main and first metabolite of methyl parathion [38
Graphical Abstract
Figure 1: Structures of G agents.
Figure 2: Scavenger based on a heterodifunctionalized β-cyclodextrin derivative.
Figure 3: Structures of β-cyclodextrin derivatives 2–5.
Figure 4: Structures of pesticides tested.
Scheme 1: Synthetic pathway to derivatives 2 and 3 (Tr = trityl).
Scheme 2: Synthesis of compound 4.
Scheme 3: Synthesis of compound 5 (Tr = trityl).
Figure 5: Hydrolysis of methyl paraoxon (0.5 mM) in the presence of compounds 1, 2, 3 or 2-iodosobenzoic acid...
Figure 6: Hydrolysis of methyl paraoxon (0.5 mM) in the presence of compounds 1, 2, 3 or 2-iodosobenzoic acid...
Figure 7: Hydrolysis of methyl paraoxon (0.5 mM) in the presence of compounds 2, 4, 5 or 2-iodosobenzoic acid...
Figure 8: Hydrolysis of methyl paraoxon (0.5 mM) in the presence of mixtures of compounds 4, 5 with IBA or im...
Figure 9: Influence of the pesticide structure on the hydrolytic efficiency of compound 2 (0.25 mM). Kinetic ...
Figure 10: Influence of TRIMEB, IBA and imidazole on the hydrolysis of methyl parathion (0.5 mM). The final co...
Figure 11: Ability of compounds 1–4 in preventing the inhibition of acetylcholinesterase by soman (GD).
Polyketide stereocontrol: a study in chemical biology
- Kira J. Weissman
Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39
- ] and hydroxy-/methoxymalonyl-ACP [42] are generated via multi-step pathways from a primary metabolite, with the intermediates tethered to a discrete ACP domain. The building blocks are then transferred onto the AT domains of the PKS, and from there to the downstream integral ACP to participate in chain
Graphical Abstract
Figure 1: Structures of clinically-relevant polyketides: erythromycin A (1), azithromycin (2), clarithromycin...
Figure 2: Schematic of erythromycin A (1) bound to 23S ribosomal RNA of the 50S subunit of the Deinococcus ra...
Figure 3: Schematic of the biosynthetic pathway leading to erythromycin A (1) in the bacterium Saccharopolysp...
Figure 4: Schematic of the virginiamycin PKS from Streptomyces virginiae, a member of the trans-AT PKS family ...
Figure 5: Determination of the stereochemistry of extender unit selection by the AT domains of modular PKS. a...
Figure 6: Creation by genetic engineering of the DEBS 1-TE model system. The region of the eryAIII gene encod...
Figure 7: Model for substrate selection by AT domains. a) Sequence motifs in malonyl- and methylmalonyl-CoA-s...
Figure 8: Proposed mechanism for KS-catalyzed chain extension, based on extrapolation from studies on homolog...
Figure 9: Experiment in vitro to determine the stereochemistry of condensation in modular PKS [46]. Use of specif...
Figure 10: Genetic engineering experiments which suggested a role for the KS domain in epimerization. a) A dik...
Figure 11: Models for control of the stereochemistry of reduction by KR domains. The two directions of ketored...
Figure 12: Assays in vitro to evaluate the stereospecificity of recombinant KR domains. A series of KR domains...
Figure 13: Assays in vitro which provided the first direct evidence that KR domains act as epimerases [77]. Biosyn...
Figure 14: Assays in vitro to demonstrate directly the epimerase activity of PKS KR domains. a) Equilibrium ex...
Figure 15: Model for DH-catalyzed generation of trans and cis double bonds by syn elimination from substrates ...
Figure 16: Stereospecificity of dehydration by Rif DH10 [94]. a) The four possible diastereomeric diketide-ACP sub...
Figure 17: Stereocontrol by PKS ER domains. Sequence motifs correlated with the final stereochemistry of the C...
Figure 18: a) PKS engineered to test the role of the ER stereospecificity residues [115]. TKS-ERY4 was created by r...
Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis
- Darcy J. Atkinson,
- Briar J. Naysmith,
- Daniel P. Furkert and
- Margaret A. Brimble
Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226
- mechanism is operative [31]. Indole metabolite In 1996, during a screening program for biologically active metabolites from marine ascidians, Riguera et al. identified a small group of amino acid containing compounds in a cytotoxic extract of the ascidian Leptoclinides dubius [32]. Among these compounds was
- the unique enduracididine-containing bromoindole metabolite 11 (Figure 4). This was the first time the enduracididine motif had been isolated from a marine source. The exact compound responsible for the observed cytotoxicity was not determined. Mannopeptimycins Mannopeptimycins α–ε (12–16, Figure 5
Graphical Abstract
Figure 1: Structures of the enduracididine family of amino acids (1–6).
Figure 2: Enduracidin A (7) and B (8).
Figure 3: Minosaminomycin (9) and related antibiotic kasugamycin (10).
Figure 4: Enduracididine-containing compound 11 identified in a cytotoxic extract of Leptoclinides dubius [32].
Figure 5: Mannopeptimycins α–ε (12–16).
Figure 6: Regions of the mannopeptimycin structure investigated in structure–activity relationship investigat...
Figure 7: Teixobactin (17).
Scheme 1: Proposed biosynthesis of L-enduracididine (1) and L-β-hydroxyenduracididine (5).
Scheme 2: Synthesis of enduracididine (1) by Shiba et al.
Scheme 3: Synthesis of protected enduracididine diastereomers 31 and 32.
Scheme 4: Synthesis of the C-2 azido diastereomers 36 and 37.
Scheme 5: Synthesis of 2-azido-β-hydroxyenduracididine derivatives 38 and 39.
Scheme 6: Synthesis of protected β-hydroxyenduracididine derivatives 40 and 41.
Scheme 7: Synthesis of C-2 diastereomeric amino acids 46 and 47.
Scheme 8: Synthesis of protected β-hydroxyenduracididines 51 and 52.
Scheme 9: General transformation of alkenes to cyclic sulfonamide 54 via aziridine intermediate 53.
Scheme 10: Synthesis of (±)-enduracididine (1) and (±)-allo-enduracididine (3).
Scheme 11: Synthesis of L-allo-enduracididine (3).
Scheme 12: Synthesis of protected L-allo-enduracididine 63.
Scheme 13: Synthesis of β-hydroxyenduracididine derivative 69.
Scheme 14: Synthesis of minosaminomycin (9).
Scheme 15: Retrosynthetic analysis of mannopeptimycin aglycone (77).
Scheme 16: Synthesis of protected amino acids 87 and 88.
Scheme 17: Synthesis of mannopeptimycin aglycone (77).
Scheme 18: Synthesis of N-mannosylation model guanidine 92 and attempted synthesis of benzyl protected mannosy...
Scheme 19: Synthesis of benzyl protected mannosyl D-β-hydroxyenduracididine 97.
Scheme 20: Synthesis of L-β-hydroxyenduracididine 98.
Scheme 21: Total synthesis of mannopeptimycin α (12) and β (13).
Scheme 22: Synthesis of protected L-allo-enduracididine 102.
Scheme 23: The solid phase synthesis of teixobactin (17).
Scheme 24: Retrosynthesis of the macrocyclic core 109 of teixobactin (17).
Scheme 25: Synthesis of macrocycle 117.
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
- both fragments of the polypropionate metabolite dolabriferol from a common precursor. The endoperoxide 304 was converted into ketone 305 with the help of the pseudo-enantiomeric quinine-derived catalyst (deMeQ-Ac) in toluene with moderate 47% yield. The peroxide 306 was transformed into ketone 307 with
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.
Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity
- Atul A. Dhavan,
- Rahul D. Kaduskar,
- Loana Musso,
- Leonardo Scaglioni,
- Piera Anna Martino and
- Sabrina Dallavalle
Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159
- Veterinary Medicine - Microbiology and Immunology, Università degli Studi di Milano, via Celoria 10, I-20133 Milano, Italy 10.3762/bjoc.12.159 Abstract The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and
- ]. Chemical analysis of a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of the plant Juniperus excelsa yielded a new metabolite, leopolic acid A (1, Figure 1) [2]. Leopolic acid has unprecedented structural features consisting of an aliphatic side chain attached to a 2,3-pyrrolidinedione
Graphical Abstract
Figure 1: Structure of leopolic acid A.
Scheme 1: Synthesis of leopolic acid A. Reagents and conditions: a) p-methoxybenzylamine, EtOH, rt, 12 h, 98%...
Scheme 2: Synthesis of compound 17. Reagents and conditions: a) Oxalyl chloride, DMSO, CH2Cl2, TEA, −78 °C to...
Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene
- Frederick J. Seidl and
- Noah Z. Burns
Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129
- regio- and enantioselectivity. Disclosed herein, this discovery has enabled the first total synthesis of (−)-anverene (1) (Scheme 1, bottom), a secondary metabolite from the algae Plocamium cartilagineum with selective antibiotic activity against vancomycin-resistant Enterococcus faecium (VREF) [10
Graphical Abstract
Scheme 1: Selective bromochlorination and possible disconnections for anverene (1).
Scheme 2: Selective total synthesis of (−)-anverene. Reagents and conditions: a) NBS (1.2 equiv), ClTi(OiPr)3...
Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides
- Andrew W. Truman
Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120
- for a number of characterised secondary metabolite pathways. For example, the bottromycin gene cluster encodes two stand-alone YcaO domain proteins that have been postulated to participate in heterocyclisation reactions [10][11][12][13]. Lanthionine bond formation in lanthipeptides Lanthipeptides
- that have been characterised for both RiPPs and for other secondary metabolite pathways, but it is interesting to note that there are a significant number of biochemical modifications that, thus far, appear to be unique to RiPP biosynthesis. For example, lanthionine formation, YcaO protein-catalysed
Graphical Abstract
Figure 1: Schematic of RiPP biosynthesis. Thiazole/oxazole formation is represented by the blue heterocycle (...
Figure 2: Examples of heterocycles in RiPPs alongside the precursor peptides that these molecules derive from...
Figure 3: Formation of thiazoles and oxazoles in RiPPs. A) Biosynthesis of microcin B17. B) Mechanistic model...
Figure 4: Lanthionine bond formation. A) Nisin and its precursor peptide. B) Mechanism of lanthionine bond fo...
Figure 5: S-[(Z)-2-Aminovinyl]-D-cysteine (AviCys) formation in the epidermin pathway. A) Mechanisms for deca...
Figure 6: Cyclisation in the biosynthesis of thiopeptides. A) Mechanism of TclM-catalysed heterocyclisation i...
Figure 7: ATP-dependent macrocyclisation. A) General mechanism for ATP-dependent macrolactonisation or macrol...
Figure 8: Peptidase-like macrolactam formation. A) General mechanism. B) Examples of RiPPs cyclised by serine...
Figure 9: Structure of autoinducing peptide AIP-I from Staphylococcus aureus and the sequence of the correspo...
Figure 10: Radical cyclisation in RiPP biosynthesis. A) AlbA-catalysed formation of thioethers in the biosynth...
Figure 11: RiPPs with uncharacterised mechanisms of cyclisation. Unusual heterocycles in ComX and methanobacti...
Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites
- Antonio Dávila-Céspedes,
- Peter Hufendiek,
- Max Crüsemann,
- Till F. Schäberle and
- Gabriele M. König
Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96
- that large genomes often correlate with the potential for prolific secondary metabolite production by revealing almost 8.6% of the genome to be possibly involved in the biosynthesis of secondary metabolites [36]. Mining this genome for the presence of PKS and NRPS genes exposed 18 biosynthetic clusters
- of compounds that have recently been shown to have antiproliferative effects on leukemic K-562 cells [27]. Halotolerant and halophilic marine myxobacteria are poorly investigated regarding secondary metabolite production. Therefore, the pool of secondary metabolites isolated from organisms of this
- osmolytes like betaine and ectoine were detected in the halotolerant bacterium. Taxonomy, cultivation and secondary metabolite chemistry of marine-derived myxobacteria (Nannocystineae) The following sections summarize features of three halotolerant and three marine-derived bacterial taxa clustered in the
Graphical Abstract
Figure 1: Structures of cystobactamids 507, 919-1 and 919-2.
Figure 2: Structures of aurafuron A and corallopyronin A.
Figure 3: Structures of ixabepilone and capecitabine.
Figure 4: Structures of DKxanthene-534 and myxochelin A.
Figure 5: Phylogenetic tree of halotolerant and halophilic myxobacteria. The neighbor-joining tree is based o...
Figure 6: Structure of nannocystin A.
Figure 7: Structure of phenylnannolones A–C.
Figure 8: Structures of the pyrronazols, dihydroxyphenazin and 1-hydroxyphenazin-6-yl-α-D-arabinofuranoside.
Figure 9: Structures of nannozinones A + B and nannochelin A from N. pusilla strain MNa10913.
Figure 10: Structure of haliangicin from H. ochraceum.
Figure 11: Structure of haliamide from H. ochraceum SMP-2.
Figure 12: Structures of salimabromide, enhygrolides A + B and salimyxins A + B.
Figure 13: Structures of miuraenamides A–F from P. miuraensis.
Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography
- Luíse Azevedo,
- Larissa Faqueti,
- Marina Kritsanida,
- Antonia Efstathiou,
- Despina Smirlis,
- Gilberto C. Franchi Jr,
- Grégory Genta-Jouve,
- Sylvie Michel,
- Louis P. Sandjo,
- Raphaël Grougnet and
- Maique W. Biavatti
Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68
- aglycone to be a sesquiterpene [33]. Based on previous reports, the signals of a CH group at δ 2.12/65.2 (C-10) and a quaternary carbon at δ 53.8 (C-6) observed in the NMR spectra of compound 1 suggested a trixane scaffold for this secondary metabolite [34]. C-10 and C-6 are respectively shared by two and
Graphical Abstract
Figure 1: UPLC profile of the butanol fraction of the leaves of Jungia sellowii after shaking the flask with ...
Figure 2: Structures of compounds 1–3.
Figure 3: COSY and HMBC correlations of compounds 1–3.
Figure 4: NOESY correlations of compounds 1–3.
Figure 5: ECD spectra of compounds 1–3.
Antibiotics from predatory bacteria
- Juliane Korp,
- María S. Vela Gurovic and
- Markus Nett
Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58
- presence of putative secondary metabolite gene clusters using the publicly available online tool antiSMASH 3.0 [51]. This analysis revealed that all strains possess extraordinary capacities for natural product assembly. Interestingly, however, the number of biosynthetic loci is not linearly correlated with
- the genome size. The largest number of secondary metabolite gene clusters was found in Corallococcus coralloides DSM 2259 and not in the two Sorangium cellulosum strains, although the latter feature significantly larger genomes (Table 1). When the number of detected loci is related to the genome size
- of biosynthesis gene clusters provide no information about the identity or biological role of the associated natural products, we note that predatory myxobacteria possess a higher density of secondary metabolite gene clusters in their genomes than their non-predatory relatives. But are these clusters
Graphical Abstract
Figure 1: Natural products isolated from M. xanthus DK1622. DKxanthene-534 (1); myxalamid B (2); myxovirescin...
Figure 2: Vegetative cells of P. fallax HKI 727 under a phase-contrast microscope (K. Martin, unpublished). B...
Figure 3: Structures of myxopyronins A (11) and B (12), corallopyronins A (13), B (14) and C (15), as well as...
Figure 4: Structure of althiomycin (17).
Figure 5: Structures of cystobactamids 919-1 (18), 919-2 (19), and 507 (20).
Figure 6: Structures of natural products isolated from Herpetosiphon spp.: siphonazole (21); auriculamide (22...
Biosynthesis of α-pyrones
- Till F. Schäberle
Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56
- temperature. Alternaria spp. had also been linked to a poultry disease outbreak called poultry hemorrhagic syndrome. However, the main toxic effects seem to be linked to other toxins produced, e.g., the non pyrone metabolite tenuazonic acid [20]. Nevertheless, alternariol (17) and altenuene (18) were studied
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])...
Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation
- Franziska Gille and
- Andreas Kirschning
Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55
- of myxovalargin (1), a secondary metabolite from Myxococcus fulvus with antibacterial activity [14][15], we report on copper-mediated cross-coupling chemistry to create peptide fragments bearing dehydrovaline and dehydroisoleucine. We faced difficulties to use the reported conditions for the C–N
Graphical Abstract
Scheme 1: Selected examples of oligopeptides bearing dehydroamino acid moieties: myxovalargin (1), argyrin A (...
Scheme 2: The Buchwald cross-coupling reaction in the preparation of peptides containing dehydroamino acids 4....
Scheme 3: Syntheses of vinyl iodides 10 and 11.
Scheme 4: Preparation of vinyl iodides 24–29 (Cbz = benzyloxycarbonyl, Alloc = allyloxycarbonyl, Boc = tert-b...
Scheme 5: Copper-mediated C–N cross-coupling of dehydropeptides 31–33, 36, 37, and 39–41.
Scheme 6: C–N coupling reaction between amide 43 and vinyl iodide 42; formation of dehydroisoleucine containi...
Natural products from microbes associated with insects
- Christine Beemelmanns,
- Huijuan Guo,
- Maja Rischer and
- Michael Poulsen
Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34
- molecular analysis of the biosynthetic gene cluster of pederin (3) [49][50][51][52]. Beetle larvae hatching from pederin-containing eggs were less prone to predation by wolf spiders than pederin-free larvae, indicating the ecological significance of this secondary metabolite [53]. The biosynthetic gene
- moiety with a pyran ring. A follow-up study via genomic analysis and metabolomic profiles revealed that piperazic acid-containing cyclic depsipeptides are very common in this ecological niche of ant-associated bacteria. Fermentation and purification of metabolite extracts of three ant-associated
- typical for all other attine ant fungi. The fungus was found to produce several antifungal diketopiperazines (e.g., 33) [114]. In another study, also reported by Clardy and co-workers, the secondary metabolite profile of the symbiotic fungus Bionectria sp. associated with the fungus-growing ant
Graphical Abstract
Figure 1: Flow chart of the typical characterization of chemical signals from microbial interactions. (1) Che...
Figure 2: Multilateral microbe–insect interactions. (1) Insect–symbiont interactions with both partners benef...
Figure 3: a) Interactions between bacterial (endo)symbionts and insects with both partners benefiting from th...
Figure 4: Multilateral microbial interactions in fungus-growing insects. (1) Insect cultivar: protects and sh...
Figure 5: Small molecules (chemical mediators) play key roles in maintaining garden homeostasis in fungus-gro...
Figure 6: Secondary metabolites isolated from Actinobacteria from fungus-growing termites. Microtermolide A (...
Figure 7: Secondary metabolites from bacterial mutualists of solitary insects. Bafilomycin A1 (21), bafilomyc...
Figure 8: Beneficial interactions (1) between fungal symbionts and insects.
Figure 9: Secondary metabolites isolated from fungal symbionts. Cerulenin (30), helvolic acid (31), lepiochlo...
Figure 10: Predatory interactions, (1) entomopathogenic fungi use insect as prey.
Figure 11: Entomopathogenic fungi use secondary metabolites as insecticidal compounds to kill their prey. Dest...
Synthesis of cyclic N1-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells
- Ahmed Mahal,
- Stefano D’Errico,
- Nicola Borbone,
- Brunella Pinto,
- Agnese Secondo,
- Valeria Costantino,
- Valentina Tedeschi,
- Giorgia Oliviero,
- Vincenzo Piccialli and
- Gennaro Piccialli
Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289
- ]. Among these NNs there is the cyclic ADP-ribose (cADPR 1, Figure 1), a metabolite strictly involved in the homeostasis of cellular calcium ions. cADPR is a second messenger that activates the ryanodine receptors of the sarcoplasmic reticulum and mobilizes Ca2+ ions in many cell types of protozoa, plants
- [17]. Using the Aplysia ADP-ribosyl cyclase many metabolite analogues of cADPR have been produced starting from NAD+ and NADP+ [18][19][20][21]. However, the specificity of the enzymatic cyclization mechanism drastically limits its applicability for enzymatic or chemo-enzymatic procedures. For this
Graphical Abstract
Figure 1: Structures of cADPR (1), cIDPR (2), cpIDP (3) and cpIMP (4).
Figure 2: Synthetic strategies explored in the cyclization step via phosphodiester bond formation.
Scheme 1: i) (iPr)2NP(OCE)Cl, DIPEA, THF, 1 h, rt; ii) 1) 1H-tetrazole, THF, 2) t-BuOOH, 2 h, rt; iii) 1) (iP...
Scheme 2: i) DNCB, K2CO3, DMF, 4 h, 80 °C; ii) 5-aminopentan-1-ol, DMF, 16 h, 50 °C; iii) Ac2O, pyridine, 2 h...
Figure 3: Effect of 3 and 4 on intracellular [Ca2+] in NGF-differentiated PC12 cells. (A) and (B): representa...
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
- endogenous metabolite of the most common estrogen hormone, 17β-estradiol, has been intensively studied owing to its proven potent antiangiogenic, antiproliferative and antitumoral activities [2][3]. However, its poor bioavailability has retarded its development as a drug [4][5]. Although recent reports of
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...
Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms
- Tatjana Huber,
- Lara Weisheit and
- Thomas Magauer
Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273
- . Although the key 2,3-Wittig–Still rearrangement proceeded in low yield and further improvements are necessary, a promising route towards the synthesis of umbellacetal (114) and xenibellol (15) was thus established. Yao and co-workers have investigated a synthetic approach towards the soft coral metabolite
Graphical Abstract
Figure 1: a) Structure of xenicin (1) and b) numbering of the xenicane skeleton according to Schmitz and van ...
Figure 2: Overview of selected Xenia diterpenoids according to the four subclasses [2-20]. The nine-membered carboc...
Figure 3: Representative members of the caryophyllenes, azamilides and Dictyota diterpenes.
Scheme 1: Proposed biosynthesis of Xenia diterpenoids (OPP = pyrophosphate, GGPP = geranylgeranyl pyrophospha...
Scheme 2: Direct synthesis of the nine-membered carbocycle as proposed by Schmitz and van der Helm (E = elect...
Scheme 3: The construction of E- or Z-cyclononenes.
Scheme 4: Total synthesis of racemic β-caryophyllene (22) by Corey.
Scheme 5: Total synthesis of racemic β-caryophyllene (22) by Oishi.
Scheme 6: Total synthesis of coraxeniolide A (10) by Leumann.
Scheme 7: Total synthesis of antheliolide A (18) by Corey.
Scheme 8: a) Synthesis of enantiomer 80, b) total syntheses of coraxeniolide A (10) and c) β-caryophyllene (22...
Scheme 9: Total synthesis of blumiolide C (11) by Altmann.
Scheme 10: Synthesis of a xeniolide F precursor by Hiersemann.
Scheme 11: Synthesis of the xenibellol (15) and the umbellacetal (114) core by Danishefsky.
Scheme 12: Proposed biosynthesis of plumisclerin A (118).
Scheme 13: Synthesis of the tricyclic core structure of plumisclerin A by Yao.
Scheme 14: Total synthesis of 4-hydroxydictyolactone (137) by Williams.
Scheme 15: Photoisomerization of 4-hydroxydictyolactone (137) to 4-hydroxycrenulide (138).
Scheme 16: The total synthesis of (+)-acetoxycrenulide (151) by Paquette.
Recent highlights in biosynthesis research using stable isotopes
- Jan Rinkel and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271
- of the metabolite did not prove to be suitable for broader applications, and therefore, after the discovery of the isotopes by Frederick Soddy, for which he was awarded the Nobel prize in 1921, the first labeling experiments using isotopes quickly changed the way of investigating metabolic pathways
Graphical Abstract
Figure 1: Structures of lovastatin (1), aflatoxin B1 (2) and amphotericin B (3).
Scheme 1: a) Structure of rhizoxin (4). b) Two possible mechanisms of chain branching catalysed by a branchin...
Scheme 2: Structure of coelimycin P1 (8) and proposed biosynthetic formation from the putative PKS produced a...
Scheme 3: Structure of trioxacarcin A (9) with highlighted carbon origins of the polyketide core from acetate...
Scheme 4: Proposed biosynthetic assembly of clostrubin A (12). Bold bonds show intact acetate units.
Figure 2: Structure of forazoline A (13).
Figure 3: Structures of tyrocidine A (14) and teixobactin (15).
Figure 4: Top: Structure of the NRPS product kollosin A (16) with the sequence N-formyl-D-Leu-L-Ala-D-Leu-L-V...
Scheme 5: Proposed biosynthesis of aspirochlorine (20) via 18 and 19.
Scheme 6: Two different macrocyclization mechanisms in the biosynthesis of pyrrocidine A (24).
Figure 5: Structure of thiomarinol A (27). Bold bonds indicate carbon atoms derived from 4-hydroxybutyrate.
Figure 6: Structures of artemisinin (28), ingenol (29) and paclitaxel (30).
Figure 7: The revised (31) and the previously suggested (32) structure of hypodoratoxide and the structure of...
Figure 8: Structure of the two interconvertible conformers of (1(10)E,4E)-germacradien-6-ol (34) studied with...
Scheme 7: Proposed cyclization mechanism of corvol ethers A (42) and B (43) with the investigated reprotonati...
Scheme 8: Predicted (top) and observed (bottom) 13C-labeling pattern in cyclooctatin (45) after feeding of [U-...
Scheme 9: Proposed mechanism of the cyclooctat-9-en-7-ol (52) biosynthesis catalysed by CotB2. Annotated hydr...
Scheme 10: Cyclization mechanism of sesterfisherol (59). Bold lines indicate acetate units; black circles repr...
Scheme 11: Cyclization mechanisms to pentalenene (65) and protoillud-6-ene (67).
Scheme 12: Reactions of chorismate catalyzed by three different enzyme subfamilies. Oxygen atoms originating f...
Scheme 13: Incorporation of sulfur into tropodithietic acid (72) via cysteine.
Scheme 14: Biosynthetic proposal for the starter unit of antimycin biosynthesis. The hydrogens at positions R1...
Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale
- Janne Weisell,
- Jouko Vepsäläinen and
- Petri A. Turhanen
Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237
- -methylbut-3-enyl)triphosphoric acid diester] (1) are described. ApppI is an active metabolite of the mevalonate pathway and thus is of major biological significance. Chemically synthezised ApppI was purified by using triethylammonium bicarbonate as the counter ion in ion-pair chromatography and
- synthesize the very important metabolite ApppI (1) have been described and for the first time, the methods are described in detail. ApppI is a rather interesting compound which is known to exert several unique biological effects and it is possible that novel properties await discovery. Now we can produce
- ApppI at a multi-milligram scale which will be important in advancing research into this interesting metabolite. Experimental 1H, 31P and 13C NMR spectra were recorded on a 500 MHz spectrometer operating at 500.1, 202.5 and 125.8 MHz, respectively. Dimethyl phosphorochloridate (3) is commercially
Graphical Abstract
Figure 1: Examples of non-N-BPs and N-BPs.
Scheme 1: Synthesis of ApppI (1).
Scheme 2: Synthesis of 3-methylbut-3-en-1-yl (trimethylsilyl) phosphorochloridate (2).
The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine
- Christine Cychon,
- Ellen Lichte and
- Matthias Köck
Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220
- alkaloids (PIAs), the citrinamines A–D (1–4) and the bromopyrrole alkaloid N-methylagelongine (5). All citrinamines are dimers of hymenidin (6) which was also isolated from this sponge as the major metabolite. Citrinamines A (1) and B (2) are derivatives of the PIA dimer mauritiamine (7), whereas
Graphical Abstract
Figure 1: Selected pyrrole-imidazole alkaloids (1–4, 6–11, and 13–20), and agelongine analogues (5, 12, and 21...
Figure 2: Selected 1H,1H-COSY (blue bonds), 1H,1H-NOESY (blue arrows), 1H,13C-HMBC, and 1H,15N-HMBC (both red...
Figure 3: Selected 1H,1H-COSY (blue bonds), 1H,1H-NOESY (blue arrows), 1H,13C-HMBC, and 1H,15N-HMBC (both red...
Figure 4: Selected 1H,1H-COSY (blue bonds), 1H,1H-NOESY (blue arrows), and 1H,13C-HMBC (red arrows) correlati...
Figure 5: Selected 1H,1H-COSY (blue bonds), 1H,1H-NOESY (blue arrows), 1H,13C-HMBC, and 1H,15N-HMBC (both red...
Figure 6: Selected 1H,1H-COSY (blue bonds), 1H,13C-HMBC, and 1H,15N-HMBC (both red arrows) correlations for N...
Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners
- Mohamed Ramadan El Sayed Aly,
- Hosam Ali Saad and
- Shams Hashim Abdel-Hafez
Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208
- II, were triggered to release bioactive coumarines by photolysis at 350 nm [14]. Dendrogenin A (DDA, III) is a natural metabolite in healthy mammals. It arises from conjugation of 5,6α-epoxycholesterol (5,6α-EC) with histamine. In vitro studies showed that DDA induced tumor cell re-differentiation
- ]. Chitinases are special enzymes involved in processing this valuable metabolite. Therefore, triazolocholesterol–glucopyranosylamine conjugates 16, 17 and 20 (Scheme 4) were prepared to compare the pharmacological effects of the modification of the D-glucopyranose moiety in VI (Figure 1) as glucosamine in
Graphical Abstract
Figure 1: Structure of ceragenin (CSA-8) and selected cholesterol conjugates.
Scheme 1: Reagents and conditions: (a) CBr4, PPh3, DCM (74%); (b) NaN3, DMF, 100 °C (63%); (c) CuSO4·5H2O, L-...
Scheme 2: Reagents and conditions: (a) NaN3, DMF, 100 °C (9b, 47%); (b) CuSO4·5H2O, L-AsAc, THF/H2O [11a, n =...
Scheme 3: Reagents and conditions: CuSO4·5H2O, L-AsAc, THF/H2O (96%).
Scheme 4: Reagents and conditions: (a) 1, TMSOTF, CH3CN, rt (74%); (b) NaOMe, MeOH (84%); (c) NaOH; HCl (pH 5...
Scheme 5: Reagents and conditions: (a) 9a, TMSOTF, DCM, rt (19%); (b) 10, CuSO4·5H2O, L-AsAc, THF/H2O (62%); ...
Scheme 6: Reagents & conditions: (a) Propargyl bromide, NaH, Et2O/DMF (quant. for both 26 and 30); (b) 3, CuSO...
Scheme 7: Reagents and conditions: (a) Bu2SnO, MeOH; propargyl bromide, TBAI, Tol (92%); (b) CuSO4·5H2O, L-As...
Figure 2: In vitro antimicrobial activity of some new cholesterol derivatives against E.coli, S. aureus. A. f...
Figure 3: Cytotoxicity effect of some new cholesterol derivatives on the PC3 cell line. Doxorubicin (Dox) was...
Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity
- Louis P. Sandjo,
- Victor Kuete and
- Maique W. Biavatti
Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183
- to a substructure that could be considered complete with the aforementioned observation. Furthermore, the assignment of the 13C shifts of a new, isolated metabolite could be made by comparing with those compiled in Table 6, where the mass spectrometry data provides information on the elemental
- ]. Synthesis of ascididemin (42) The first synthesis of ascididemin was performed in 1992 by Moody et al. [64] and included four steps with an overall yield of 21%. Recently, the same secondary metabolite was prepared by six efficient steps which afforded a yield two-fold (45%) of that of the previous
- using phosphoryl bromide. Another organozinc substrate was coupled to the obtained intermediate by a Negishi cross-coupling and cyclisation occurred to give the expected secondary metabolite (Scheme 8) [68]. The yield of the last step in the preparation of 9 could be improved by using the synthetic
Graphical Abstract
Figure 1: Fragments produced by the FAB–MS of dehydrokuanoniamine B (20) [42].
Figure 2: Fragments produced by the EIMS of sagitol (26) [55].
Figure 3: Fragments produced by the EIMS of styelsamine B (4) [45].
Figure 4: Fragments produced by the EIMS of styelsamine D (6) [45].
Figure 5: Fragments produced by the EIMS of subarine (37) [40].
Scheme 1: Synthesis of styelsamine B (4) and cystodytin J (1) [58].
Scheme 2: Synthesis of sebastianine A (38) and its regioisomer 39 [59].
Scheme 3: Synthesis route A of neoamphimedine (12) [61].
Scheme 4: Synthesis route B of neoamphimedine (12) [62].
Scheme 5: Synthesis of arnoamines A (40) and B (41) [63].
Scheme 6: Synthesis of ascididemin (42) [65].
Scheme 7: Synthesis of subarine (37) [66,67].
Scheme 8: Synthesis of demethyldeoxyamphimedine (9) [68].
Scheme 9: Synthesis of pyridoacridine analogues related to ascididemin (42) [70].
Scheme 10: Synthesis of analogues of meridine (56) [71].
Scheme 11: Synthesis of bulky pyridoacridine as eilatin (58) [72].
Scheme 12: Synthesis of AK37 (59), analogue of kuanoniamine A (60) [73].
Figure 6: Biosynthesis pathway I [74].
Figure 7: Reaction illustrating catechol and kynuramine as possible biosynthetic precursors [75].
Figure 8: Biosynthesis pathway B deduced from the feeding experiment A using labelled precursors [76].
Figure 9: Proposed biosynthesis pathway [47].
Figure 10: 4H-Pyrido[2,3,4-kl]acridin-4-one as a cytotoxic pharmacophore.
Figure 11: 7H-Pyrido[2,3,4-kl]acridine as a cytotoxic pharmacophore.
Figure 12: 9H-Quinolino[4,3,2-de][1,10]phenanthrolin-9-one as a cytotoxic pharmacophore.
Figure 13: 8H-Benzo[b]pyrido[4,3,2-de][1,7]phenanthrolin-8-one as a cytotoxic pharmacophore.
Figure 14: Pyrido[4,3,2-mn]pyrrolo[3,2,1-de]acridine as a cytotoxic pharmacophore.
Figure 15: 9H-Pyrido[4,3,2-mn]thiazolo[4,5-b]acridin-9-one and 8H-pyrido[4,3,2-mn]thiazolo[4,5-b]acridine: cyt...
Figure 16: 9H-quinolino[4,3,2-de][1,10]phenanthrolin-9-one as an anti-mycobacterial pharmacophore.
Figure 17: 9H-Quinolino[4,3,2-de][1,10]phenanthrolin-9-one as an antibacterial pharmacophore.
Figure 18: Saturated and less saturated pyridine moieties as aspartyl inhibitor cores.
Figure 19: Iminobenzoquinone and acridone cores as intercalating and TOPO inhibitor motifs found in pyridoacri...
The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry
- Marcus Baumann and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134
- , R1 = cyclopropyl, R2 = piperazinyl) [44]. An important early industry-based example was disclosed by scientists at Bristol-Myers Squibb in 2008 detailing a flow approach towards converting the psychotropic agent buspirone (7) into its major active metabolite, 6-hydroxybuspirone (9) [45]. This work
Graphical Abstract
Figure 1: Pharmaceutical structures targeted in early flow syntheses.
Scheme 1: Flow synthesis of 6-hydroxybuspirone (9). Inserted photograph reprinted with permission from [45]. Copy...
Figure 2: Configuration of a baffled reactor tube (left) and its schematic working principle (right).
Scheme 2: McQuade’s flow synthesis of ibuprofen (16).
Scheme 3: Jamison’s flow synthesis of ibuprofen sodium salt (17).
Scheme 4: Flow synthesis of imatinib (23).
Scheme 5: Flow synthesis of the potent 5HT1B antagonist 28.
Scheme 6: Flow synthesis of a selective δ-opioid receptor agonist 33.
Scheme 7: Flow synthesis of a casein kinase I inhibitor library (38).
Scheme 8: Flow synthesis of fluoxetine (46).
Scheme 9: Flow synthesis of artemisinin (55).
Scheme 10: Telescoped flow synthesis of artemisinin (55) and derivatives (62–64).
Scheme 11: Flow approach towards AZD6906 (65).
Scheme 12: Pilot scale flow synthesis of key intermediate 73.
Scheme 13: Semi-flow synthesis of vildagliptine (77).
Scheme 14: Pilot scale asymmetric flow hydrogenation towards 83. Inserted photograph reprinted with permission...
Figure 3: Schematic representation of the ‘tube-in-tube’ reactor.
Scheme 15: Flow synthesis of fanetizole (87) via tube-in-tube system.
Scheme 16: Flow synthesis of diphenhydramine.HCl (92).
Scheme 17: Flow synthesis of rufinamide (95).
Scheme 18: Large scale flow synthesis of rufinamide precursor 102.
Scheme 19: First stage in the flow synthesis of meclinertant (103).
Scheme 20: Completion of the flow synthesis of meclinertant (103).
Scheme 21: Flow synthesis of olanzapine (121) utilising inductive heating techniques.
Scheme 22: Flow synthesis of amitriptyline·HCl (127).
Scheme 23: Flow synthesis of E/Z-tamoxifen (132) using peristaltic pumping modules.
Figure 4: Container sized portable mini factory (photograph credit: INVITE GmbH, Leverkusen Germany).
Scheme 24: Flow synthesis of imidazo[1,2-a]pyridines 136 linked to frontal affinity chromatography (FAC).
Figure 5: Structures of zolpidem (142) and alpidem (143).
Scheme 25: Synthesis and screening loops in the discovery of new Abl kinase inhibitors.
Figure 6: Schotten–Baumann approach towards LY573636.Na (147).
Scheme 26: Pilot scale flow synthesis of LY2886721 (146).
Scheme 27: Continuous flow manufacture of alikiren hemifumarate 152.
(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues
- Armin de Meijere,
- Sergei I. Kozhushkov,
- Dmitrii S. Yufit,
- Christian Grosse,
- Marcel Kaiser and
- Vitaly A. Raev
Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302
- (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity. Keywords: amino acids; biosynthesis; building blocks; cyclopropanes; natural products; synthetic methods; Introduction The intermolecular signal metabolite hormaomycin (1, Figure 1) was first
- provided close to 20 hormaomycin analogues that have contributed to an understanding of the biosynthetic pathways, the conformational behavior in solution and the structure–activity relationship. After the initial observation that hormaomycin (1) has a marked influence on the secondary metabolite
Graphical Abstract
Figure 1: Structure and absolute configuration of hormaomycin (1), its fluoromethyl-substituted analogues 8a–c...
Figure 2: Structures of the Belokon'-type glycine complexes (BGC) (R)- and (S)-10.
Scheme 1: Intended routes to methyl trans-2-(fluormethyl)cyclopropanecarboxylates 14a–c.
Scheme 2: Synthesis of trans-(2-trifluoromethyl)cyclopropanecarboxylic acid (24).
Scheme 3: Preparation of racemic trans-2-(fluoromethyl)cyclopropylmethyl iodides 11a–c and their conversion t...
Figure 3: Structure and absolute configurations of the nickel(II) complexes (2S,1'R,2'S)-26a, (2S,1'R,2'S)-26b...
Figure 4: Structure and absolute configuration of nickel(II) complex (R,R,R)-28 in the crystal. Hydrogen atom...
Scheme 4: Mechanism of epimerization of the threonine nickel(II) complex 29.
Scheme 5: A new general approach to (2S,3R)-β-methylarylalanines 3 by alkylation of the glycine nickel(II) co...
Figure 5: Structure and absolute configuration of nickel(II) complex (2S,3S)-32 in the crystal. Hydrogen atom...
Scheme 6: Synthesis of the cyclohexadepsipeptides 52a–c for the hormaomycin analogues 8a–c with 3-(2'-fluorom...
Scheme 7: Synthesis of hormaomycin analogues with a: trifluoromethyl-, b: difluoromethyl-, c: monofluoromethy...
Figure 6: Two derivatives 58 and 59 of cyclohexadepsipeptide 52a containing the (trifluoromethylcyclopropyl)a...
Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3
- Zhi Kai Guo,
- Rong Wang,
- Wei Huang,
- Xiao Nian Li,
- Rong Jiang,
- Ren Xiang Tan and
- Hui Ming Ge
Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282
- liquid fermentation broth of Aspergillus sp. YXf3 and isolated a novel norditerpenoid, namely, aspergiloid I (1) (Figure 1). Herein, we report the production, isolation, structure characterization, and biological activity of 1, a rare spirolactone metabolite with a novel carbon skeleton. Results and
Graphical Abstract
Figure 1: Structure of aspergiloid I (1) and its novel skeleton.
Figure 2: Selected 1H,1H-COSY and HMBC correlations and key NOEs observed for 1.
Figure 3: X-ray single-crystal structure of 1.
Scheme 1: Proposed biosynthetic pathway of 1.
