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Search for "Staudinger reaction" in Full Text gives 26 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence
- Long Zhao,
- Mao-Lin Yang,
- Min Liu and
- Ming-Wu Ding
Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32
- /addition/nucleophilic substitution reactions. Keywords: aza-Wittig reaction; 3,4-dihydroquinazoline; 4H-3,1-benzothiazine; nucleophilic substitution; Passerini reaction; Staudinger reaction; Introduction The chemistry of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines is of constant interest owing to
- . Compound 4a was then allowed to react with triphenylphosphine in CH2Cl2 at room temperature for 2 h to produce the iminophosphorane 5a by Staudinger reaction. Aza-Wittig reaction of 5a with phenyl isocyanate generated carbodiimide 6a, which was then treated with diethylamine to form the guanidine
Graphical Abstract
Figure 1: Some bioactive 3,4-dihydroquinazolines and 4H-3,1-benzothiazines.
Scheme 1: Representative preperation of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines.
Scheme 2: Preparation of 3,4-dihydroquinazoline 8a.
Scheme 3: Preparation of 3,4-dihydroquinazolines 8.
Scheme 4: Preparation of 4H-3,1-benzothiazines 11.
N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts
- Viera Poláčková,
- Dominika Krištofíková,
- Boglárka Némethová,
- Renata Górová,
- Mária Mečiarová and
- Radovan Šebesta
Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176
- after each step prompted us to apply a Mitsunobu and Staudinger reaction for the preparation of amine 2 (Scheme 1) [33]. This one-pot reaction gave the desired amine 2 in 56% yield. Then, the corresponding isothiocyanate 3a was prepared by reaction of amine 2 with CS2 and DCC according to the reported
Graphical Abstract
Figure 1: Catalyst design principles.
Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
Scheme 3: Synthesis of adducts 8a,d,f in solution.
Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
- Mathias B. Danielsen and
- Jesper Wengel
Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125
- -aminopropyl)aminoethyl (88) PS linkage was too heat-labile for nuclease tests [117]. Filichev and co-workers have recently synthesized a variant of the phosphoramidate internucleotide linkage (Table 9B) and have obtained some preliminary results. Modification 91 was introduced via Staudinger reaction during
Graphical Abstract
Figure 1: A schematic representation of 16-mer ASOs in different designs. White circles represent unmodified ...
Figure 2: Structures of 5-(1-propargylamino)-2’-deoxyuridine (A) and 2’-aminoethoxy-5-propargylaminouridine (...
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
- Nikita Brodyagin,
- Martins Katkevics,
- Venubabu Kotikam,
- Christopher A. Ryan and
- Eriks Rozners
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
Graphical Abstract
Figure 1: Structure of DNA and PNA.
Figure 2: PNA binding modes: (A) PNA–dsDNA 1:1 triplex; (B) PNA–DNA–PNA strand-invasion triplex; (C) the Hoog...
Figure 3: Structure of P-form PNA–DNA–PNA triplex from reference [41]. (A) view in the major groove and (B) view ...
Figure 4: Structures of backbone-modified PNA.
Figure 5: Structures of PNA having α- and γ-substituted backbones.
Figure 6: Structures of modified nucleobases in PNA to improve Hoogsteen hydrogen bonding to guanine and aden...
Figure 7: Proposed hydrogen bonding schemes for modified PNA nucleobases designed to recognize pyrimidines or...
Figure 8: Modified nucleobases to modulate Watson–Crick base pairing and chemically reactive crosslinking PNA...
Figure 9: Examples of triplets formed by Janus-wedge PNA nucleobases (blue). R1 denotes DNA, RNA, or PNA back...
Figure 10: Examples of fluorescent PNA nucleobases. R1 denotes DNA, RNA, or PNA backbones.
Figure 11: Endosomal entrapment and escape pathways of PNA and PNA conjugates.
Figure 12: (A) representative cell-penetrating peptides (CPPs), (B) conjugation designs and linker chemistries....
Figure 13: Proposed delivery mode by pHLIP-PNA conjugates (A) the transmembrane section of pHLIP interacting w...
Figure 14: Structures of modified penetratin CPP conjugates with PNA linked through either disulfide (for stud...
Figure 15: Chemical structure of C9–PNA, a stable amphipathic (cyclic-peptide)–PNA conjugate.
Figure 16: Structures of PNA conjugates with a lipophilic triphenylphosphonium cation (TPP–PNA) through (A) th...
Figure 17: Structures of (A) chloesteryl–PNA, (B) cholate–PNA and (C) cholate–PNA(cholate)3.
Figure 18: Structures of PNA–GalNAc conjugates (A) (GalNAc)2K, (B) triantennary (GalNAc)3, and (C) trivalent (...
Figure 19: Vitamin B12–PNA conjugates with different linkages.
Figure 20: Structures of (A) neomycin B, (B) PNA–neamine conjugate, and (C) PNA–neosamine conjugate.
Figure 21: PNA clamp (red) binding to target DNA containing a mixture of sequences (A) PNA binds with higher a...
Figure 22: Rolling circle amplification using PNA openers (red) to invade a dsDNA target forming a P-loop. A p...
Figure 23: Molecular beacons containing generic fluorophores (Fl) and quenchers (Q) recognizing a complementar...
Figure 24: (A) Light-up fluorophores such as thiazole orange display fluorescence enhancement upon binding to ...
Figure 25: Templated fluorogenic detection of oligonucleotides using two PNAs. (A) Templated FRET depends on h...
Figure 26: Lateral flow devices use a streptavidin labeled strip on nitrocellulose paper to anchor a capture P...
DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies
- Yongdong Su,
- Maitsetseg Bayarjargal,
- Tracy K. Hale and
- Vyacheslav V. Filichev
Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65
- modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to
- transfection reagent, whereas, N+ONs remain concentrated in vesicles within the cytoplasm. These results indicate that both N+ and Ts-modified ONs are promising for various in vivo applications. Keywords: cell uptake; charge neutral modification; DNA; modified phosphates; Staudinger reaction; Introduction
- one or more N-modified phosphoramidate groups (Scheme 1, III) were obtained after the removal of the protective groups and β-cyanoethyl groups using ≈28% ammonia. We found out that a higher conversion was observed when performing the Staudinger reaction at 37 °C rather than at room temperature. The
Graphical Abstract
Figure 1: Illustration of H-bonding in a DNA duplex and a parallel triplex. A) Depiction of Watson–Crick base...
Scheme 1: The synthesis of ONs with Ts and N+ modification using the Staudinger reaction during the solid-pha...
Figure 2: Percentage of intact ONs after 120 min. A) N+ONs; B) Ts-ONs. Percentage of intact ONs was determine...
Figure 3: Representative images of mouse NIH 3T3 fibroblasts incubated with either (A–C) no oligo or 20 µM of...
Figure 4: Representative confocal microscopy section showing the FAM vesicles inside the cell. Mouse NIH 3T3 ...
N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds
- Iwona E. Głowacka,
- Aleksandra Trocha,
- Andrzej E. Wróblewski and
- Dorota G. Piotrowska
Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168
- (Scheme 32) [85]. The reaction involved a nucleophilic displacement at more hindered C2 with inversion of configuration to form the azido ester (2S,1'R)-126 which was transformed into (S)-125 in usual way. However, since amines can be obtained from azides by a Staudinger reaction the ester (2S,1'R)-126
Graphical Abstract
Figure 1: Examples of three-carbon chirons.
Figure 2: Structures of derivatives of N-(1-phenylethyl)aziridine-2-carboxylic acid 5–8.
Figure 3: Synthetic equivalency of aziridine aldehydes 6.
Scheme 1: Synthesis of N-(1-phenylethyl)aziridine-2-carboxylates 5. Reagents and conditions: a) TEA, toluene,...
Scheme 2: Absolute configuration at C2 in (2S,1'S)-5a. Reagents and conditions: a) 20% HClO4, 80 °C, 30 h the...
Scheme 3: Major synthetic strategies for a 2-ketoaziridine scaffold [R* = (R)- or (S)-1-phenylethyl; R′ = Alk...
Scheme 4: Synthesis of cyanide (2S,1'S)-13. Reagents and conditions: a) NH3, EtOH/H2O, rt, 72 h; b) Ph3P, CCl4...
Scheme 5: Synthesis of key intermediates (R)-16 and (R)-17 for (R,R)-formoterol (14) and (R)-tamsulosin (15)....
Scheme 6: Synthesis of mitotic kinesin inhibitors (2R/S,1'R)-23. Reagents and conditions: a) H2, Pd(OH)2, EtO...
Scheme 7: Synthesis of (R)-mexiletine ((R)-24). Reagents and conditions: a) TsCl, TEA, DMAP, CH2Cl2, rt, 1 h;...
Scheme 8: Synthesis of (−)-cathinone ((S)-27). Reagents and conditions: a) PhMgBr, ether, 0 °C; b) H2, 10% Pd...
Scheme 9: Synthesis of N-Boc-norpseudoephedrine ((1S,2S)-(+)-29) and N-Boc-norephedrine ((1R,2S)-29). Reagent...
Scheme 10: Synthesis of (−)-ephedrine ((1R,2S)-31). Reagents and conditions: a) TfOMe, MeCN then NaBH3CN, rt; ...
Scheme 11: Synthesis of xestoaminol C ((2S,3R)-35), 3-epi-xestoaminol C ((2S,3S)-35) and N-Boc-spisulosine ((2S...
Scheme 12: Synthesis of ʟ-tryptophanol ((S)-41). Reagents and conditions: a) CDI, MeCN, rt, 1 h then TMSI, MeC...
Scheme 13: Synthesis of ʟ-homophenylalaninol ((S)-42). Reagents and conditions: a) NaH, THF, 0 °C to −78 °C, 1...
Scheme 14: Synthesis of ᴅ-homo(4-octylphenyl)alaninol ((R)-47) and a sphingolipid analogue (R)-48. Reagents an...
Scheme 15: Synthesis of florfenicol ((1R,2S)-49). Reagents and conditions: a) (S)-1-phenylethylamine, TEA, MeO...
Scheme 16: Synthesis of natural tyroscherin ((2S,3R,6E,8R,10R)-55). Reagents and conditions: a) I(CH2)3OTIPS, t...
Scheme 17: Syntheses of (−)-hygrine (S)-61, (−)-hygroline (2S,2'S)-62 and (−)-pseudohygroline (2S,2'R)-62. Rea...
Scheme 18: Synthesis of pyrrolidine (3S,3'R)-68, a fragment of the fluoroquinolone antibiotic PF-00951966. Rea...
Scheme 19: Synthesis of sphingolipid analogues (R)-76. Reagents and conditions: a) BnBr, Mg, THF, reflux, 6 h;...
Scheme 20: Synthesis of ᴅ-threo-PDMP (1R,2R)-81. Reagents and conditions: a) TMSCl, NaI, MeCN, rt, 1 h 50 min,...
Scheme 21: Synthesis of the sphingolipid analogue SG-14 (2S,3S)-84. Reagents and conditions: a) LiAlH4, THF, 0...
Scheme 22: Synthesis of the sphingolipid analogue SG-12 (2S,3R)-88. Reagents and conditions: a) 1-(bromomethyl...
Scheme 23: Synthesis of sphingosine-1-phosphate analogues DS-SG-44 and DS-SG-45 (2S,3R)-89a and (2S,3R)-89a. R...
Scheme 24: Synthesis of N-Boc-safingol ((2S,3S)-95) and N-Boc-ᴅ-erythro-sphinganine ((2S,3R)-95). Reagents and...
Scheme 25: Synthesis of ceramide analogues (2S,3R)-96. Reagents and conditions: a) NaBH4, ZnCl2, MeOH, −78 °C,...
Scheme 26: Synthesis of orthogonally protected serinols, (S)-101 and (R)-102. Reagents and conditions: a) BnBr...
Scheme 27: Synthesis of N-acetyl-3-phenylserinol ((1R,2R)-105). Reagents and conditions: a) AcOH, CH2Cl2, refl...
Scheme 28: Synthesis of (S)-linezolid (S)-107. Reagents and conditions: a) LiAlH4, THF, 0 °C to reflux; b) Boc2...
Scheme 29: Synthesis of (2S,3S,4R)-2-aminooctadecane-1,3,4-triol (ᴅ-ribo-phytosphingosine) (2S,3S,4R)-110. Rea...
Scheme 30: Syntheses of ᴅ-phenylalanine (R)-116. Reagents and conditions: a) AcOH, CH2Cl2, reflux, 4 h; b) MsC...
Scheme 31: Synthesis of N-Boc-ᴅ-3,3-diphenylalanine ((R)-122). Reagents and conditions: a) PhMgBr, THF, −78 °C...
Scheme 32: Synthesis of ethyl N,N’-di-Boc-ʟ-2,3-diaminopropanoate ((S)-125). Reagents and conditions: a) NaN3,...
Scheme 33: Synthesis of the bicyclic amino acid (S)-(+)-127. Reagents and conditions: a) BF3·OEt2, THF, 60 °C,...
Scheme 34: Synthesis of lacosamide, (R)-2-acetamido-N-benzyl-3-methoxypropanamide (R)-130. Reagents and condit...
Scheme 35: Synthesis of N-Boc-norfuranomycin ((2S,2'R)-133). Reagents and conditions: a) H2C=CHCH2I, NaH, THF,...
Scheme 36: Synthesis of MeBmt (2S,3R,4R,6E)-139. Reagents and conditions: a) diisopropyl (S,S)-tartrate (E)-cr...
Scheme 37: Synthesis of (+)-polyoxamic acid (2S,3S,4S)-144. Reagents and conditions: a) AD-mix-α, MeSO2NH2, t-...
Scheme 38: Synthesis of the protected 3-hydroxy-ʟ-glutamic acid (2S,3R)-148. Reagents and conditions: a) LiHMD...
Scheme 39: Synthesis of (+)-isoserine (R)-152. Reagents and conditions: a) AcCl, MeCN, rt, 0.5 h then Na2CO3, ...
Scheme 40: Synthesis of (3R,4S)-N3-Boc-3,4-diaminopentanoic acid (3R,4S)-155. Reagents and conditions: a) Ph3P...
Scheme 41: Synthesis of methyl (2S,3S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoate (2S,3S,4S)-159. ...
Scheme 42: Syntheses of methyl (3S,4S) 4,5-di-N-Boc-amino-3-hydroxypentanoate ((3S,4S)-164), methyl (3S,4S)-4-N...
Scheme 43: Syntheses of (3R,5S)-5-(aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one ((3R,5S)-168). Reage...
Scheme 44: Syntheses of a series of imidazolin-2-one dipeptides 175–177 (for R' and R'' see text). Reagents an...
Scheme 45: Syntheses of (2S,3S)-N-Boc-3-hydroxy-2-hydroxymethylpyrrolidine ((2S,3S)-179). Reagents and conditi...
Scheme 46: Syntheses of enantiomers of 1,4-dideoxy-1,4-imino-ʟ- and -ᴅ-lyxitols (2S,3R,4S)-182 and (2R,3S,4R)-...
Scheme 47: Synthesis of 1,4-dideoxy-1,4-imino-ʟ-ribitol (2S,3S,4R)-182. Reagents and conditions: a) AcOH, CH2Cl...
Scheme 48: Syntheses of 1,4-dideoxy-1,4-imino-ᴅ-arabinitol (2R,3R,4R)-182 and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ...
Scheme 49: Syntheses of natural 2,5-imino-2,5,6-trideoxy-ʟ-gulo-heptitol ((2S,3R,4R,5R)-184) and its C4 epimer...
Scheme 50: Syntheses of (−)-dihydropinidine ((2S,6R)-187a) (R = C3H7) and (2S,6R)-isosolenopsins (2S,6R)-187b ...
Scheme 51: Syntheses of (+)-deoxocassine ((2S,3S,6R)-190a, R = C12H25) and (+)-spectaline ((2S,3S,6R)-190b, R ...
Scheme 52: Synthesis of (−)-microgrewiapine A ((2S,3R,6S)-194a) and (+)-microcosamine A ((2S,3R,6S)-194b). Rea...
Scheme 53: Syntheses of ʟ-1-deoxynojirimycin ((2S,3S,4S,5R)-200), ʟ-1-deoxymannojirimycin ((2S,3S,4S,5S)-200) ...
Scheme 54: Syntheses of 1-deoxy-ᴅ-galacto-homonojirimycin (2R,3S,4R,5S)-211. Reagents and conditions: a) MeONH...
Scheme 55: Syntheses of 7a-epi-hyacinthacine A1 (1S,2R,3R,7aS)-220. Reagents and conditions: a) TfOTBDMS, 2,6-...
Scheme 56: Syntheses of 8-deoxyhyacinthacine A1 ((1S,2R,3R,7aR)-221). Reagents and conditions: a) H2, Pd/C, PT...
Scheme 57: Syntheses of (+)-lentiginosine ((1S,2S,8aS)-227). Reagents and conditions: a) (EtO)2P(O)CH2COOEt, L...
Scheme 58: Syntheses of 8-epi-swainsonine (1S,2R,8S,8aR)-231. Reagents and conditions: a) Ph3P=CHCOOMe, MeOH, ...
Scheme 59: Synthesis of a protected vinylpiperidine (2S,3R)-237, a key intermediate in the synthesis of (−)-sw...
Scheme 60: Synthesis of a modified carbapenem 245. Reagents and conditions: a) AcOEt, LiHMDS, THF, −78 °C, 1.5...
Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials
- Widukind Moormann,
- Daniel Langbehn and
- Rainer Herges
Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68
- deprotection with TiCl4 the hydroxy-functionalized diazocines 4a and 4b were obtained [32]. The hydroxy groups in 4a and 4b were successfully converted into azides using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) and DBU [33]. The synthesis was completed with a Staudinger reaction to obtain
Graphical Abstract
Figure 1: (a) Isomerization of parent diazocine 1. Distances of carbon atoms para to the ethylene bridge were...
Figure 2: Synthesized target diazocines 4–7 for applications in responsive materials.
Scheme 1: Key reactions in diazocine synthesis.
Scheme 2: Syntheses of the functionalized diazocines 4–7. Reaction conditions: i) Isobutylene, sulfuric acid,...
Figure 3: UV–vis spectra of 3,3’-diaminodiazocine 2 (left), 3,3’-di(aminomethyl)diazocine 6a (center), and 3,...
Enzyme-free genetic copying of DNA and RNA sequences
- Marilyne Sosson and
- Clemens Richert
Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47
- , the 3'-amine was protected with an azidomethyloxycarbonyl (Azoc) protecting group. This protecting group can be rapidly removed under non-denaturing conditions after incorporation by the complementary nucleotide using the Staudinger reaction with a water-soluble phosphine (Figure 11). This protocol
Graphical Abstract
Figure 1: Enzyme-free template-directed extension of an RNA primer by one nucleotide. B = nucleobase, LG = le...
Figure 2: Oligomerization of the 2-methylimidazolide of guanosine-5'-monophosphate on a poly(C) template.
Figure 3: Structures of backbone linkages produced in enzyme-free primer extension reactions: the phosphorami...
Figure 4: System used for studying the template effect with all 64 possible triplets at the extension site (B...
Figure 5: Interactions attracting the incoming nucleotide to the extension site. Besides base pairing via hyd...
Figure 6: Three possible fates of activated nucleotides in aqueous buffer that result from hydrolysis, primer...
Figure 7: Steps and equilibria considered in our quantitative model of chemical primer extension [34]. The model ...
Figure 8: Binding equilibrium between mononucleotides and hairpins representing primer–template duplexes, as ...
Figure 9: Template-directed primer extension on an RNA template performed with OAt-GMP at 1.8 mM (orange), 3....
Figure 10: Copying of four nucleotides on an immobilized RNA duplex, as reported by Deck et al. [32].
Figure 11: Extension cycle of aminoterminal primer with N-protected nucleotides on solid support, as described...
Figure 12: Formation of a highly reactive methylimidazolium bisphosphate from methylimidazolides of nucleotide...
Figure 13: 31P NMR spectrum (161.9 MHz) of crude MeIm-GMP in D2O. The resonance of the imidazolium bisphosphat...
Figure 14: Imidazolium bisphosphate as intermediate in the primer extension reaction, as described by Szostak ...
Figure 15: Proposed steps of enzyme-free primer extension with in situ activation, using the "general condensa...
Fluorogenic PNA probes
- Tirayut Vilaivan
Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17
- the unmasking of quenched or caged fluorophores by chemical reactions, such as the Staudinger reaction [98][99][100][101], hydrolysis [102] and group transfer mediated by nucleophilic substitution [103][104]. Optimizing the conditions requires a good balance between the affinity of the probe to the
Graphical Abstract
Figure 1: The design of classical DNA molecular beacons.
Figure 2: Structures of DNA and selected PNA systems.
Figure 3: Various binding modes of PNA to double stranded DNA including triplex formation, triplex invasion, ...
Figure 4: The design and working principle of the PNA beacons according to (A) Ortiz et al. [41] and (B) Armitage...
Figure 5: The design of "stemless" PNA beacons.
Figure 6: The applications of PNA openers to facilitate the binding of PNA beacons to double stranded DNA [40,47].
Figure 7: The working principle of snap-to-it probes that employed metal chelation to bring the dyes in close...
Figure 8: Examples of pre-formed dye-labeled PNA monomers and functionalizable PNA monomers.
Figure 9: Dual-labeled PNA beacons with end-stacking or intercalating quencher.
Figure 10: The working principle of hybrid PNA-peptide beacons for detection of (A) proteins [80] and (B) protease...
Figure 11: The working principle of binary probes.
Figure 12: The working principle of nucleic acid templated fluorogenic reactions leading to a (A) ligated prod...
Figure 13: Catalytic cycles in fluorogenic nucleic acid templated reactions [90].
Figure 14: The working principle of strand displacement probes.
Figure 15: (A) Examples of CPP successfully used with labeled PNA probes. (B) The use of single-labeled PNA pr...
Figure 16: The concept of PNA–GO platform for DNA/RNA sensing.
Figure 17: Single-labeled fluorogenic PNA probes.
Figure 18: Examples of environment sensitive fluorescent labels that have been incorporated into PNA probes as...
Figure 19: The mechanism of fluorescence change in TO dye.
Figure 20: Fluorescent nucleobases capable of hydrogen bonding that have been incorporated into PNA probes.
Figure 21: Comparison of the designs of the (A) light-up PNA probe and (B) FIT PNA probe.
Figure 22: The structures of TO and its analogues that have successfully been used in FIT PNA probes.
Figure 23: The working principle of dual-labeled FIT PNA probes [222,223].
Aminosugar-based immunomodulator lipid A: synthetic approaches
- Alla Zamyatina
Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3
Graphical Abstract
Figure 1: (A) Gram-negative bacterial membrane with LPS as major component of the outer membrane; (B) structu...
Figure 2: Structures of representative TLR4 ligands: TLR4 agonists (E. coli lipid A, N. meningitidis lipid A ...
Figure 3: (A) Co-crystal structure of the homodimeric E. coli Ra-LPS·hMD-2∙TLR4 complex (PDB code: 3FXI); (B)...
Figure 4: Co-crystal structures of (A) hybrid TLR4·hMD-2 with the bound antagonist eritoran (PDB: 2Z65, TLR4 ...
Scheme 1: Synthesis of E. coli and S. typhimurium lipid A and analogues with shorter acyl chains.
Scheme 2: Synthesis of N. meningitidis Kdo-lipid A.
Scheme 3: Synthesis of fluorescently labeled E. coli lipid A.
Scheme 4: Synthesis of H. pylori lipid A and Kdo-lipid A.
Scheme 5: Synthesis of tetraacylated lipid A corresponding to P. gingivalis LPS.
Scheme 6: Synthesis of pentaacylated P. gingivalis lipid A.
Scheme 7: Synthesis of monophosphoryl lipid A (MPLA) and analogues.
Scheme 8: Synthesis of tetraacylated Rhizobium lipid A containing aminogluconate moiety.
Scheme 9: Synthesis of pentaacylated Rhizobium lipid A and its analogue containing ether chain.
Scheme 10: Synthesis of pentaacylated Rhizobium lipid A containing 27-hydroxyoctacosanoate lipid chain.
Scheme 11: Synthesis of zwitterionic 1,1′-glycosyl phosphodiester: a partial structure of GalN-modified Franci...
Scheme 12: Synthesis of a binary 1,1′-glycosyl phosphodiester: a partial structure of β-L-Ara4N-modified Burkh...
Scheme 13: Synthesis of Burkholderia lipid A containing binary glycosyl phosphodiester linked β-L-Ara4N.
A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway
- Dmitry Yu. Vandyshev,
- Khidmet S. Shikhaliev,
- Andrey Yu. Potapov,
- Michael Yu. Krysin,
- Fedor I. Zubkov and
- Lyudmila V. Sapronova
Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252
- a result of their direct heterocyclization involving various single-carbon electrophilic reagents [15][16][20]. A similar one-pot aza-Staudinger reaction of 3-(azidomethyl)pyridazines with isothiocyanates in the presence of PMe3 also results in imidazopyridazines [17]. In the synthesis of imidazo
Graphical Abstract
Scheme 1: Intramolecular cyclization of 3-(aminomethyl)pyridazines and related compounds (route A). Condition...
Scheme 2: Heterocyclization of 1-aminoimidazoles with 1,3-dicarbonyl or α,β-unsaturated carbonyl compounds (r...
Scheme 3: Heterocyclization of 1-aminoimidazoles with structural transformation of dielectrophilic reagents (...
Scheme 4: Recyclization of N-arylitaconimides 1 with 1,2-diaminobenzimidazole (2).
Scheme 5: Possible synthetic routes of the interaction of itaconimides 1 with diaminoimidazole 4.
Scheme 6: 1H,13C-HMBC correlations: the most significant correlations for imidazopyridazine 9d and possible f...
Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics
- Matthias Wünsch,
- David Schröder,
- Tanja Fröhr,
- Lisa Teichmann,
- Sebastian Hedwig,
- Nils Janson,
- Clara Belu,
- Jasmin Simon,
- Shari Heidemeyer,
- Philipp Holtkamp,
- Jens Rudlof,
- Lennard Klemme,
- Alessa Hinzmann,
- Beate Neumann,
- Hans-Georg Stammler and
- Norbert Sewald
Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240
- -protected S-methylisothiourea to yield the arginine analogous propargylamine 7x in a yield of 79%. During the decomposition of the azide in the Staudinger reaction, the TMS group at the alkyne was cleaved off simultaneously. Cleavage of TMS groups with PPh3 under similar conditions has not been reported so
Graphical Abstract
Figure 1: Concept of carboxylic acid or amide bond replacement on the basis of an alkyne moiety.
Figure 2: Selection of reactions based on propargylamines as precursors. a) Intramolecular Pauson–Khand react...
Figure 3: Two different approaches for the stereoselective de novo synthesis of propargylamines using Ellman’...
Figure 4: Synthesis of propargylamines 4a and 4b by introducing the side chain as nucleophile. (a) HC≡CCH2OH,...
Figure 5: Reaction of N-sulfinylimine 5h with (trimethylsilyl)ethynyllithium. (a) GP-3 or GP-4. (b) Aqueous w...
Figure 6: Side reactions observed in the course of the conversion of highly electrophilic sulfinylimines 5. (...
Figure 7: a) Possible transition states TI and TII for the transfer of the methyl moiety from AlMe3 to the im...
Figure 8: Base-induced rearrangement of propargylamines bearing electron-withdrawing substituents.
Figure 9: Base-catalyzed rearrangement of propargylamines 11 to α,β-unsaturated imines 12. A) Reaction scheme...
Enabling technologies and green processes in cyclodextrin chemistry
- Giancarlo Cravotto,
- Marina Caporaso,
- Laszlo Jicsinszky and
- Katia Martina
Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30
- azido β-CD was obtained by a Staudinger reaction or in the presence of hydrazine. A new generation of organophosphate scavengers has been obtained by Le Provost et al. [25] in which β-CD was regioselectively monosubstituted at O-2 using a bromomethyl pyridine derivative under US irradiation to avoid
Graphical Abstract
Figure 1: (a) Multihorn-flow US reactor, (b) Cavitational turbine, (c) Pilot-scale BM, (d) High-pressure MW r...
Figure 2: Trends in CD papers and CD use in green chemical processes.
Figure 3: Distribution of energy efficient methods in CD publications.
Figure 4: Document type dealing with CD chemistry under non-conventional techniques (conference proceedings a...
Figure 5: Document type dealing with sustainable technologies in CD publications.
Scheme 1: Synthesis of 6I-(p-toluenesulfonyl)-β-CD.
Scheme 2: Example of CuAAC with 6I-azido-6I-deoxy-β-CD and phenylacetylene.
Scheme 3: Synthesis of 6I-benzylureido-6I-deoxy-per-O-acetyl-β-CD.
Scheme 4: Synthesis of 3I-azido-3I-deoxy-altro-α, β- and γ-CD.
Scheme 5: Synthesis of 2-2’ bridged bis(β-CDs). Reaction conditions: 1) TBDMSCl, imidazole, dry pyridine, sti...
Scheme 6: Insoluble reticulated CD polymer.
Scheme 7: CD-HDI cross linked polymers.
Scheme 8: Derivatization of 6I-(p-toluenesulfonyl)-β-CD by tosyl displacement.
Scheme 9: Synthetic scheme for the preparation of heptakis(6-amino-6-deoxy)-β-CD, heptakis(6-deoxy-6-ureido)-...
Scheme 10: Structure of CD derivatives obtained via MW-assisted CuAAC.
Scheme 11: Preparation of SWCN CD-DOTA carrier.
Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors
- Morgan Hans,
- Jan Lorkowski,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252
- tetrafluoroborate without any apparent complication [59]. We have further optimized this procedure on the occasion of a mechanistic study of the Staudinger reaction catalyzed by NHC·ketene zwitterions (Scheme 5) [60]. Synthesis of 1,3-dimesitylimidazolinium chloride The “saturated” analogue of the IMes carbene, 1,3
Graphical Abstract
Scheme 1: Various synthetic paths leading to the formation of NHCs.
Scheme 2: Retrosynthetic path for the preparation of symmetrical imidazolium and imidazolinium salts from sim...
Figure 1: Structures of the imidazolium and imidazolinium salts discussed in this study and their acronyms.
Scheme 3: Synthesis of 1,3-dicyclohexylimidazolium tetrafluoroborate (ICy·HBF4).
Scheme 4: Synthesis of 1,3-dibenzylimidazolium tetrafluoroborate (IBn·HBF4).
Scheme 5: Synthesis of 1,3-dimesitylimidazolium salts (IMes·HCl and IMes·HBF4).
Scheme 6: Synthesis of 1,3-dimesitylimidazolinium chloride (SIMes·HCl).
Scheme 7: Synthesis of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IDip·HCl).
Scheme 8: Synthesis of 1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (SIDip·HCl).
Scheme 9: Synthesis of 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazolium chloride (IDip*·HCl).
Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries
- Markus Nörrlinger and
- Thomas Ziegler
Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256
- nitro group was achieved with a Staudinger reaction [14]. Thus, treatment of 5 with triphenylphosphine in aqueous THF gave tert-butyl 3-aminomethyl-5-nitrobenzoate which was not isolated but immediately converted into the corresponding Fmoc-protected derivative 6 in 78% overall yield. Final
Graphical Abstract
Figure 1: Malonyl-linked aromatic glycoconjugate building blocks for spot synthesis of combinatorial glycopep...
Scheme 1: Synthesis of the aromatic backbone building blocks 7 and 9.
Scheme 2: Synthesis of dimers 17, 20, 22 and 24.
Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions
- Andreas Gansäuer,
- Andreas Okkel,
- Lukas Schwach,
- Laura Wagner,
- Anja Selig and
- Aram Prokop
Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169
- A–D shown in Figure 2 were used as amino-substituted azides. They are readily obtained from the corresponding diazides through a Staudinger reaction (see Supporting Information File 1 for details) [45][46]. As for the carboxylates the different tether lengths and substitution patterns of the arene
Graphical Abstract
Scheme 1: Modular titanocene synthesis via acylation reactions [24].
Figure 1: Carboxylates employed as titanocene starting materials for azide-substituted complexes.
Figure 2: Azides employed in this study and conditions for their synthesis.
Figure 3: Most active titanocenes of this study and their AC50 values.
Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ0)
- Sabin Llona-Minguez and
- Simon P. Mackay
Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135
- both alcohols showed a diastereomeric purity of >99% by 1H NMR. Mitsunobu reaction on the secondary alcohols using DEAD or DIAD did not provide the desired azides [42][43] nor did a one-pot Appel reaction/nucleophilic substitution/Staudinger reaction protocol involving a double inversion of
Graphical Abstract
Figure 1: Biosynthetic pathway leading to nucleosides queuosine and archaeosine.
Figure 2: Chemical structure of noraristeromycin.
Figure 3: Synthesis of PreQ0 and chloro-intermediate 9. Reagents and conditions: (a) Methyl formate, NaOMe, P...
Figure 4: Synthesis of 15, a (1RS,2SR,3RS)-3-aminocyclopentane-1,2-diol derivative of PreQ0. Reagents and con...
Figure 5: Synthesis of 16, a (1S,2R,3S,4R)-4-aminocyclopentane-1,2,3-triol derivative of PreQ0. Reagents and ...
Figure 6: Synthesis of 21 and 22, 3-arylcyclohexylamine derivatives of PreQ0. Reagents and conditions: (a) Ph...
Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability
- Malamatenia D. Manouilidou,
- Yannis G. Lazarou,
- Irene M. Mavridis and
- Konstantina Yannakopoulou
Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73
- ) satisfactory aqueous solubility and independent binding capacity of the cavities. Keywords: calculations; conformations; cyclodextrin; dimer; inclusion; PM3; Staudinger ligation; Introduction The Staudinger reaction [1] is a classical method for the preparation of amines from phosphines and azides [2][3
- , and (c) inclusion conformation. Typical conformations of 6: (a) open conformation, (b) vicinal, (c) inclusion/vicinal and (d) double inclusion conformation. (a) Staudinger reaction (b) Staudinger ligation, (c) the cyclodextrin structure with glucopyranose unit numbering: n = 7, β-CD; H3 and H5 atoms
Graphical Abstract
Scheme 1: (a) Staudinger reaction (b) Staudinger ligation, (c) the cyclodextrin structure with glucopyranose ...
Scheme 2: (a) i) HCl, NaNO2/H2O, then KI/H2O, 58%, ii) Ph2PH, Pd(OAc)2, Et3N, MeOH, 48%; (b) i) CH3COOH, H2SO4...
Scheme 3: Staudinger ligation reactions: (a) Preparation of 4 from mono[6-(3-azidopropylamino)-6-deoxy]-β-CD ...
Figure 1: 1H NMR chemical shift change (Δδ) of CD cavity Η3 signal of compounds titrated with 1-adamantylamin...
Figure 2: The most stable conformations of 4 at the PM3(COSMO) level of theory: (a) open, (b) vicinal, and (c...
Figure 3: Typical conformations of 6: (a) open conformation, (b) vicinal, (c) inclusion/vicinal and (d) doubl...
Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin
- Rajendra S. Rohokale and
- Dilip D. Dhavale
Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59
- -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed
Graphical Abstract
Figure 1: Microginin (1) and (2S,3R)-AHDA (2a).
Scheme 1: Retrosynthetic analysis of AHDA.
Scheme 2: Synthesis of AHDA 2a.
Scheme 3: Synthesis of ent-AHDA 2b.
Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
- Gijs Koopmanschap,
- Eelco Ruijter and
- Romano V.A. Orru
Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50
- - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002
- products were obtained in excellent yields and in high diastereoselectivity when chiral imines were employed (159b, de >95%). The group of van Boom and Overkleeft reported pipecolic amides via a Staudinger–Aza-Wittig/Ugi sequence (SAWU 3CR, Scheme 51) [132]. First the Staudinger reaction between an
Graphical Abstract
Scheme 1: The proposed mechanism of the Passerini reaction.
Scheme 2: The PADAM-strategy to α-hydroxy-β-amino amide derivatives 7. An additional oxidation provides α-ket...
Scheme 3: The general accepted Ugi-mechanism.
Scheme 4: Three commonly applied Ugi/cyclization approaches. a) UDC-process, b) UAC-sequence, c) UDAC-combina...
Scheme 5: Ugi reaction that involves the condensation of Armstrong’s convertible isocyanide.
Scheme 6: Mechanism of the U-4C-3CR towards bicyclic β-lactams.
Scheme 7: The Ugi 4C-3CR towards oxabicyclo β-lactams.
Scheme 8: Ugi MCR between an enantiopure monoterpene based β-amino acid, aldehyde and isocyanide resulting in...
Scheme 9: General MCR for β-lactams in water.
Scheme 10: a) Ugi reaction for β-lactam-linked peptidomimetics. b) Varying the β-amino acid resulted in β-lact...
Scheme 11: Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization.
Scheme 12: Ugi-3CR of dipeptide mimics from 2-substituted pyrrolines.
Scheme 13: Joullié–Ugi reaction towards 2,5-disubstituted pyrrolidines.
Scheme 14: Further elaboration of the Ugi-scaffold towards bicyclic systems.
Scheme 15: Dihydroxyproline derivatives from an Ugi reaction.
Scheme 16: Diastereoselective Ugi reaction described by Banfi and co-workers.
Scheme 17: Similar Ugi reaction as in Scheme 16 but with different acids and two chiral isocyanides.
Scheme 18: Highly diastereoselective synthesis of pyrrolidine-dipeptoids via a MAO-N/MCR-procedure.
Scheme 19: MAO-N/MCR-approach towards the hepatitis C drug telaprevir.
Scheme 20: Enantioselective MAO-U-3CR procedure starting from chiral pyrroline 64.
Scheme 21: Synthesis of γ-lactams via an UDC-sequence.
Scheme 22: Utilizing bifunctional groups to provide bicyclic γ-lactam-ketopiperazines.
Scheme 23: The Ugi reaction provided both γ- as δ-lactams depending on which inputs were used.
Scheme 24: The sequential Ugi/RCM with olefinic substrates provided bicyclic lactams.
Scheme 25: a) The structural and dipole similarities of the triazole unit with the amide bond. b) The copper-c...
Scheme 26: The Ugi/Click sequence provided triazole based peptidomimetics.
Scheme 27: The Ugi/Click reaction as described by Nanajdenko.
Scheme 28: The Ugi/Click-approach by Pramitha and Bahulayan.
Scheme 29: The Ugi/Click-combination by Niu et al.
Scheme 30: Triazole linked peptidomimetics obtained from two separate MCRs and a sequential Click reaction.
Scheme 31: Copper-free synthesis of triazoles via two MCRs in one-pot.
Scheme 32: The sequential Ugi/Paal–Knorr reaction to afford pyrazoles.
Scheme 33: An intramolecular Paal–Knorr condensation provided under basic conditions pyrazolones.
Scheme 34: Similar cyclization performed under acidic conditions provided pyrazolones without the trifluoroace...
Scheme 35: The Ugi-4CR towards 2,4-disubstituted thiazoles.
Scheme 36: Solid phase approach towards thiazoles.
Scheme 37: Reaction mechanism of formation of thiazole peptidomimetics containing an additional β-lactam moiet...
Scheme 38: The synthesis of the trisubstituted thiazoles could be either performed via an Ugi reaction with pr...
Scheme 39: Performing the Ugi reaction with DMB-protected isocyanide gave access to either oxazoles or thiazol...
Scheme 40: Ugi/cyclization-approach towards 2,5-disubstituted thiazoles. The Ugi reaction was performed with d...
Scheme 41: Further derivatization of the thiazole scaffold.
Scheme 42: Three-step procedure towards the natural product bacillamide C.
Scheme 43: Ugi-4CR to oxazoles reported by Zhu and co-workers.
Scheme 44: Ugi-based synthesis of oxazole-containing peptidomimetics.
Scheme 45: TMNS3 based Ugi reaction for peptidomimics containing a tetrazole.
Scheme 46: Catalytic cycle of the enantioselective Passerini reaction towards tetrazole-based peptidomimetics.
Scheme 47: Tetrazole-based peptidomimetics via an Ugi reaction and a subsequent sigmatropic rearrangement.
Scheme 48: Resin-bound Ugi-approach towards tetrazole-based peptidomimetics.
Scheme 49: Ugi/cyclization approach towards γ/δ/ε-lactam tetrazoles.
Scheme 50: Ugi-3CR to pipecolic acid-based peptidomimetics.
Scheme 51: Staudinger–Aza-Wittig/Ugi-approach towards pipecolic acid peptidomimetics.
Figure 1: The three structural isomers of diketopiperazines. The 2,5-DKP isomer is most common.
Scheme 52: UDC-approach to obtain 2,5-DKPs, either using Armstrong’s isocyanide or via ethylglyoxalate.
Scheme 53: a) Ugi reaction in water gave either 2,5-DKP structures or spiro compounds. b) The Ugi reaction in ...
Scheme 54: Solid-phase approach towards diketopiperazines.
Scheme 55: UDAC-approach towards DKPs.
Scheme 56: The intermediate amide is activated as leaving group by acid and microwave assisted organic synthes...
Scheme 57: UDC-procedure towards active oxytocin inhibitors.
Scheme 58: An improved stereoselective MCR-approach towards the oxytocin inhibitor.
Scheme 59: The less common Ugi reaction towards DKPs, involving a Sn2-substitution.
Figure 2: Spatial similarities between a natural β-turn conformation and a DKP based β-turn mimetic [158].
Scheme 60: Ugi-based syntheses of bicyclic DKPs. The amine component is derived from a coupling between (R)-N-...
Scheme 61: Ugi-based synthesis of β-turn and γ-turn mimetics.
Figure 3: Isocyanide substituted 3,4-dihydropyridin-2-ones, dihydropyridines and the Freidinger lactams. Bio-...
Scheme 62: The mechanism of the 4-CR towards 3,4-dihydropyridine-2-ones 212.
Scheme 63: a) Multiple MCR-approach to provide DHP-peptidomimetic in two-steps. b) A one-pot 6-CR providing th...
Scheme 64: The MCR–alkylation–MCR procedure to obtain either tetrapeptoids or depsipeptides.
Scheme 65: U-3CR/cyclization employing semicarbazone as imine component gave triazine based peptidomimetics.
Scheme 66: 4CR towards triazinane-diones.
Scheme 67: The MCR–alkylation–IMCR-sequence described by our group towards triazinane dione-based peptidomimet...
Scheme 68: Ugi-4CR approaches followed by a cyclization to thiomorpholin-ones (a) and pyrrolidines (b).
Scheme 69: UDC-approach for benzodiazepinones.
Scheme 70: Ugi/Mitsunobu sequence to BDPs.
Scheme 71: A UDAC-approach to BDPs with convertible isocyanides. The corresponding amide is cleaved by microwa...
Scheme 72: microwave assisted post condensation Ugi reaction.
Scheme 73: Benzodiazepinones synthesized via the post-condensation Ugi/ Staudinger–Aza-Wittig cyclization.
Scheme 74: Two Ugi/cyclization approaches utilizing chiral carboxylic acids. Reaction (a) provided the product...
Scheme 75: The mechanism of the Gewald-3CR includes three base-catalysed steps involving first a Knoevnagel–Co...
Scheme 76: Two structural 1,4-thienodiazepine-2,5-dione isomers by U-4CR/cyclization.
Scheme 77: Tetrazole-based diazepinones by UDC-procedure.
Scheme 78: Tetrazole-based BDPs via a sequential Ugi/hydrolysis/coupling.
Scheme 79: MCR synthesis of three different tricyclic BPDs.
Scheme 80: Two similar approaches both involving an Ugi reaction and a Mitsunobu cyclization.
Scheme 81: Mitsunobu–Ugi-approach towards dihydro-1,4-benzoxazepines.
Scheme 82: Ugi reaction towards hetero-aryl fused 5-oxo-1,4-oxazepines.
Scheme 83: a) Ugi/RCM-approach towards nine-membered peptidomimetics b) Sequential peptide-coupling, deprotect...
Scheme 84: Ugi-based synthesis towards cyclic RGD-pentapeptides.
Scheme 85: Ugi/MCR-approach towards 12–15 membered macrocycles.
Scheme 86: Stereoselective Ugi/RCM approach towards 16-membered macrocycles.
Scheme 87: Passerini/RCM-sequence to 22-membered macrocycles.
Scheme 88: UDAC-approach towards 12–18-membered depsipeptides.
Figure 4: Enopeptin A with its more active derivative ADEP-4.
Scheme 89: a) The Joullié–Ugi-approach towards ADEP-4 derivatives b) Ugi-approach for the α,α-dimethylated der...
Scheme 90: Ugi–Click-strategy for 15-membered macrocyclic glyco-peptidomimetics.
Scheme 91: Ugi/Click combinations provided macrocycles containing both a triazole and an oxazole moiety.
Scheme 92: a) A solution-phase procedure towards macrocycles. b) Alternative solid-phase synthesis as was repo...
Scheme 93: Ugi/cyclization towards cyclophane based macrocycles.
Scheme 94: PADAM-strategy towards eurystatin A.
Scheme 95: PADAM-approach for cyclotheanamide.
Scheme 96: A triple MCR-approach affording RGD-pentapeptoids.
Scheme 97: Ugi-MiBs-approach towards peptoid macrocycles.
Scheme 98: Passerini-based MiB approaches towards macrocycles 345 and 346.
Scheme 99: Macrocyclic peptide formation by the use of amphoteric aziridine-based aldehydes.
Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics
- Léa Bouché,
- Maja Kandziora and
- Hans-Ulrich Reissig
Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17
- hydroxy substituents of 24 with TBS-groups, a Staudinger reaction was performed, which furnished bicyclic 1,2-oxazine derivative 25 with a primary amino group in 80% yield (over two steps). Next we wanted to synthesize the unexpectedly formed unique tricyclic 1,2-oxazine 20 with higher efficacy. After
Graphical Abstract
Scheme 1: General approach to enantiopure the poly(hydroxy)aminopyrans D (n = 0) and the aminooxepanes D (n =...
Scheme 2: Synthesis of (Z)-nitrone 3. Conditions: a) 1. p-Bromobenzaldehyde dimethylacetal, TFA, DMF, rt, 5 d...
Scheme 3: Synthesis of 1,2-oxazines syn-7, syn-9 and syn-10. Conditions: a) n-BuLi, THF, −40 °C, 15 min; b) 1...
Figure 1: Proposed transition structure for the addition of lithiated TMSE-allene 5 to chiral nitrones 3, 6 a...
Scheme 4: Synthesis of ketones 11, 12 and 13 with a bicyclic 1,2-oxazine skeleton by Lewis acid-induced rearr...
Scheme 5: Proposed extended chair-like conformation with Zimmerman–Traxler-type transition state.
Figure 2: GOESY–NMR spectrum (CDCl3, 500 MHz) of bicyclic 1,2-oxazine 13: irradiation of the 2-H proton. [GOE...
Scheme 6: Synthesis of triols 14, 15 and 16 by reduction of the carbonyl group and deprotection. Conditions: ...
Scheme 7: Synthesis of propargylic ether 18. Conditions: a) propargyl bromide, NaOH, TBAI, H2O/CH2Cl2, −20 °C...
Scheme 8: Synthesis of tricyclic compound 20, bicyclic azide 24 and bicyclic amine 25. Conditions: a) MsCl, Et...
Scheme 9: Hydrogenolyses of bicyclic and tricyclic 1,2-oxazines 14, 15 and 20 to aminooxepanes 26, 27 and 28....
Figure 3: Proposed structures of the observed side products 29 and 30 during the hydrogenolyses of 14 and 15.
Scheme 10: Hydrogenolyses of bicyclic 1,2-oxazines to aminooxepanes 26, 31 and 32 and to diaminooxepane 33 und...
Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines
- Alexander Penger,
- Cortney N. von Hahmann,
- Alexander S. Filatov and
- John T. Welch
Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303
- familiar Staudinger reaction of imines to transform readily accessible aldehydes to β-lactams has been well reviewed [30][31][32][33], yet in spite of this familiarity, the mechanism of this process remains a topic of interest [34][35][36]. Previously, it has been shown that fluorinated imines can undergo
- ]. Structural characterization of SF5-containing β-lactams Isolated as a single diastereomer, the relative stereochemistry of 7a, the product of the Staudinger reaction of 5a, is shown in Figure 1. The cis relative stereochemistry of β-lactam is consistent with 1,2-lk conrotatory ring closure of the E-imine 5a
Graphical Abstract
Scheme 1: Synthesis of 2-pentafluorosulfanylaldehydes by addition of SF5Cl to enol ethers.
Scheme 2: Reaction of pentafluorosulfanylaldimines with benzyloxyketene.
Scheme 3: Preparation of ethyl pentafluorosulfanylpyruvate and formation of the corresponding β-lactam.
Figure 1: The 1,2-lk stereochemistry of 7a as determined by single crystal X-ray diffraction. Thermal ellipso...
Scheme 4: Influence of the SF5 group on the initial attack of the ketene on the imine nitrogen (A) and on the...
Figure 2: The stereochemistry of 7c, 1,2-lk,lk (Si, Si-S), as determined by single crystal X-ray diffraction ...
An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles
- Marcus Baumann and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265
Graphical Abstract
Scheme 1: Scaled industrial processes for the synthesis of simple pyridines.
Scheme 2: Synthesis of nicotinic acid from 2-methyl-5-ethylpyridine (1.11).
Scheme 3: Synthesis of 3-picoline and nicotinic acid.
Scheme 4: Synthesis of 3-picoline from 2-methylglutarodinitrile 1.19.
Scheme 5: Picoline-based synthesis of clarinex (no yields reported).
Scheme 6: Mode of action of proton-pump inhibitors and structures of the API’s.
Scheme 7: Hantzsch-like route towards the pyridine rings in common proton pump inhibitors.
Figure 1: Structures of rosiglitazone (1.40) and pioglitazone (1.41).
Scheme 8: Synthesis of rosiglitazone.
Scheme 9: Syntheses of 2-pyridones.
Scheme 10: Synthesis and mechanism of 2-pyrone from malic acid.
Scheme 11: Polymer-assisted synthesis of rosiglitazone.
Scheme 12: Synthesis of pioglitazone.
Scheme 13: Meerwein arylation reaction towards pioglitazone.
Scheme 14: Route towards pioglitazone utilising tyrosine.
Scheme 15: Route towards pioglitazone via Darzens ester formation.
Scheme 16: Syntheses of the thiazolidinedione moiety.
Scheme 17: Synthesis of etoricoxib utilising Negishi and Stille cross-coupling reactions.
Scheme 18: Synthesis of etoricoxib via vinamidinium condensation.
Figure 2: Structures of nalidixic acid, levofloxacin and moxifloxacin.
Scheme 19: Synthesis of moxifloxacin.
Scheme 20: Synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane 1.105.
Scheme 21: Synthesis of levofloxacin.
Scheme 22: Alternative approach to the levofloxacin core 1.125.
Figure 3: Structures of nifedipine, amlodipine and clevidipine.
Scheme 23: Mg3N2-mediated synthesis of nifedipine.
Scheme 24: Synthesis of rac-amlodipine as besylate salt.
Scheme 25: Aza Diels–Alder approach towards amlodipine.
Scheme 26: Routes towards clevidipine.
Figure 4: Examples of piperidine containing drugs.
Figure 5: Discovery of tiagabine based on early leads.
Scheme 27: Synthetic sequences to tiagabine.
Figure 6: Structures of solifenacin (2.57) and muscarine (2.58).
Scheme 28: Enantioselective synthesis of solifenacin.
Figure 7: Structures of DPP-4 inhibitors of the gliptin-type.
Scheme 29: Formation of inactive diketopiperazines from cis-rotameric precursors.
Figure 8: Co-crystal structure of carmegliptin bound in the human DPP-4 active site (PDB 3kwf).
Scheme 30: Improved route to carmegliptin.
Figure 9: Structures of lamivudine and zidovudine.
Scheme 31: Typical routes accessing uracil, thymine and cytosine.
Scheme 32: Coupling between pyrimidones and riboses via the Vorbrüggen nucleosidation.
Scheme 33: Synthesis of lamivudine.
Scheme 34: Synthesis of raltegravir.
Scheme 35: Mechanistic studies on the formation of 3.22.
Figure 10: Structures of selected pyrimidine containing drugs.
Scheme 36: General preparation of pyrimidines and dihydropyrimidones.
Scheme 37: Synthesis of imatinib.
Scheme 38: Flow synthesis of imatinib.
Scheme 39: Syntheses of erlotinib.
Scheme 40: Synthesis of erlotinib proceeding via Dimroth rearrangement.
Scheme 41: Synthesis of lapatinib.
Scheme 42: Synthesis of rosuvastatin.
Scheme 43: Alternative preparation of the key aldehyde towards rosuvastatin.
Figure 11: Structure comparison between nicotinic acetylcholine receptor agonists.
Scheme 44: Syntheses of varenicline and its key building block 4.5.
Scheme 45: Synthetic access to eszopiclone and brimonidine via quinoxaline intermediates.
Figure 12: Bortezomib bound in an active site of the yeast 20S proteasome ([114], pdb 2F16).
Scheme 46: Asymmetric synthesis of bortezomib.
Figure 13: Structures of some prominent piperazine containing drugs.
Figure 14: Structural comparison between the core of aplaviroc (4.35) and a type-1 β-turn (4.36).
Scheme 47: Examplary synthesis of an aplaviroc analogue via the Ugi-MCR.
Scheme 48: Syntheses of azelastine (5.1).
Figure 15: Structures of captopril, enalapril and cilazapril.
Scheme 49: Synthesis of cilazapril.
Figure 16: Structures of lamotrigine, ceftriaxone and azapropazone.
Scheme 50: Synthesis of lamotrigine.
Scheme 51: Alternative synthesis of lamotrigine (no yields reported).
Figure 17: Structural comparison between imiquimod and the related adenosine nucleoside.
Scheme 52: Conventional synthesis of imiquimod (no yields reported).
Scheme 53: Synthesis of imiquimod.
Scheme 54: Synthesis of imiquimod via tetrazole formation (not all yields reported).
Figure 18: Structures of various anti HIV-medications.
Scheme 55: Synthesis of abacavir.
Figure 19: Structures of diazepam compared to modern replacements.
Scheme 56: Synthesis of ocinaplon.
Scheme 57: Access to zaleplon and indiplon.
Scheme 58: Different routes towards the required N-methylpyrazole 6.65 of sildenafil.
Scheme 59: Polymer-supported reagents in the synthesis of key aminopyrazole 6.72.
Scheme 60: Early synthetic route to sildenafil.
Scheme 61: Convergent preparations of sildenafil.
Figure 20: Comparison of the structures of sildenafil, tadalafil and vardenafil.
Scheme 62: Short route to imidazotriazinones.
Scheme 63: Alternative route towards vardenafils core imidazotriazinone (6.95).
Scheme 64: Bayer’s approach to the vardenafil core.
Scheme 65: Large scale synthesis of vardenafil.
Scheme 66: Mode of action of temozolomide (6.105) as methylating agent.
Scheme 67: Different routes to temozolomide.
Scheme 68: Safer route towards temozolomide.
Figure 21: Some unreported heterocyclic scaffolds in top market drugs.
(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties
- José L. Jiménez Blanco,
- Fernando Ortega-Caballero,
- Carmen Ortiz Mellet and
- José M. García Fernández
Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20
- pseudooligosaccharides having cyanamide, urea and thiourea-linkages via the Staudinger reaction have been reported [69][70]. In our group, the carbodiimide approach was used to prepare calystegine B2 analogues with the urea-linked disaccharide structure (Figure 15). These compounds, however, did not show inhibitory
Graphical Abstract
Figure 1: Schematic representation of sugar aminoacids (SAAs) and (pseudo)amide oligosaccharide mimetics.
Figure 2: Natural SAAs structures and natural nucleosidic antibiotics.
Scheme 1: Synthetic route to the target amide-linked sialooligomers. (a) Fmoc-Cl, NaHCO3, H2O, dioxane, 0 °C....
Figure 3: The general structure of glycoamino acids and their corresponding oligomers.
Figure 4: Conformational analysis of the β(1→2)-amide-linked glucooligomer 9.
Figure 5: Short oligomeric chains of C-glycosyl D-arabino THF amino acid oligomers.
Figure 6: (A) Stereoview of the minimized structure of compound 16 (produced by a 500 ps simulation) that mos...
Figure 7: Structures of linear oxetane-β- and δ-SAA homo-oligomers 19–20.
Figure 8: 10-Membered ring H-bonds in compound 21 consistent with NMR and modelling investigations.
Figure 9: General structure of carbopeptoid-oligonucleotide conjugates.
Figure 10: Protected derivatives of 2,6-diamino-2,6-dideoxy-β-D-glucopyranosyl carboxylic acid 22 and 23.
Figure 11: Cyclic homo-oligomers containing glucopyranoid-SAAs.
Scheme 2: Strategy for solid-phase synthesis of cyclic trimers and tetramers containing pyranoid δ-SAAs.
Figure 12: Cyclic tetramers of L-rhamno- and D-gulo-configured oxetane-SAAs.
Figure 13: Aminoglycosidic antibiotics of the glycocinnamoylspermidine family.
Scheme 3: Synthesis of (thio)trehazoline, via triflate, from β-hydroxy(thio)urea.
Figure 14: Approaches to access pseudoamide-type oligosaccharide mimics.
Figure 15: Calystegine B2 analogues 38 and 39 with urea-linked disaccharide structure.
Figure 16: Rotameric equilibrium shift of 40 by formation of a bidentate hydrogen bond.
Figure 17: Nucleotide analogues with thiourea and S-methylisothiouronium linkers.
Scheme 4: Retrosynthetic approach to synthesize thiourea-linked glycooligomers.
Figure 18: Rotameric equilibria for β-(1→6)-thiourea-linked glucodimer 41.
Figure 19: Schematic representation of (a) cyclodextrin (CDs) and (b) cyclotrehalan (CTs) family members.
Scheme 5: Synthesis of guanidine-linked pseudodisaccharides via carbodiimide.
Figure 20: β(1→6)-Guanidine-linked pseudodi- and pseudotrisaccharides 47 and 48.
Scheme 6: Synthesis of N-benzylguanidine-linked CT2 50.
Figure 21: Structure of RNG and DNG.
Figure 22: Preparation of Fmoc-guanidinium derivatives.
Figure 23: Structures of the homo-oligomeric RNG derivatives 51–55.
Figure 24: Phosphoramidite building block 56.
Figure 25: Structures of DNGs 57–65.
Figure 26: Structure of the phosphoramidite building block 66.
