Heterocyclic N-Glycosides. VI. The reaction of glycosyl azides with propiolic acid and methyl propiolate

The synthesis of a series of N-glycosyl-v-triazoles has been accomplished by the 1,3-dipolar cycloaddition of several glycosyl azides to methyl propiolate and propiolic acid. In most of the cases the two isomeric v-triazoles were obtained. Structural and anomeric configuration assignments for the N-glycosides obtained were made on the basis of NMR data. None of the compounds possessed appreciable biological activity against HeLa cells in culture and mouse Sarcoma 180.     

Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified Staudinger reaction

The solid-phase synthesis of glycopeptides containing the sugar at the C-terminus is reported. The method is demonstrated on a model, the endogenous antinociceptive peptide Leu-enkephalin. 2,3,4-Tri-O-acetyl-1-azido-1-deoxy-beta-D-glucopyranuronic acid was synthesized and immobilized onto a variety of derivatized resins. Conjugation of the first amino acid was accomplished by reaction of the resin-bound glycosyl azide with an activated amino acid, in one step, via a modified Staudinger reaction. Standard solid-phase peptide synthesis then resulted in the desired amide-linked glycopeptide. Reaction conditions and reagents for the glycosylation were varied to optimize the yield and purity of the product. The optimum conditions were found to be the use of a 4-fold molar excess of activated amino acid and 3-fold excess of tri-n-butylphosphine in tetrahydrofuran. This methodology is generally applicable to most peptide sequences and is compatible with both Boc- and Fmoc- synthetic strategies on a variety of resins.     

Heterocyclic N-glycosides. VIII. Anomerisation and rearrangement of 2′,3′-unsaturated N-glycosides

The acid catalyzed transformation of cither 1-(4 -O-acety1-2,3 -dideoxy-α- or β-L-glycero-pent-2 -cnosyl)-5,6-dichlorobenzotriazole gave the same mixture of unsaturuted glycosides. The main three components of this mixture were the above α and β anomers and a glycal-type compound which results from the allylic rearrangement of the 5,6-dichlorobenzotriuzole moiety to the C-3 position of the carbohydrate. Evidence is presented that these results can be rationalized as proceeding through an allylic carbonium ion. Preliminary experiments on transglycosidation reactions using 2′,3′-unsaturated N-glycosides are reported.     

Traceless Staudinger ligation of glycosyl azides with triaryl phosphines: stereoselective synthesis of glycosyl amides

Alpha-glycosyl amides can be synthesized from the corresponding O-benzyl-alpha-glycosyl azides using a traceless Staudinger ligation with diphenylphosphanyl-phenyl esters 4. All the phosphines employed and their phenol precursors are stable to air at 4 degrees C for months. Fast intramolecular trapping of the reduction intermediates results in the direct formation of the amide link, which, in turn, prevents epimerisation and allows retention of configuration at the anomeric carbon. Yields and alpha-selectivity are high when the reaction is performed in polar aprotic solvents. Removal of the benzyl ether protecting groups is achieved by catalytic hydrogenation. Alpha-glycosyl amides represent a class of virtually unexplored nonhydrolyzable monosaccharide derivatives that may find a useful application as sugar mimics. Conformational studies by NMR spectroscopy confirm that deprotected alpha-glycosyl amides in the gluco, galacto, and fuco series retain the normal pyranose conformation of the monosaccharide. The reaction of phosphines 4 with tetra-O-acetyl-glycosyl azides is nonstereoconservative, and beta-glycosyl amides are obtained in good yields and with complete stereoselectivity starting from both alpha and beta azides.     

Synthesis of N-glycosides of benzimidazole and its derivatives

N-Benzimidazolylglucopyranosides were synthesized by condensation of N-trimethylsilyl derivatives of benzimidazole and its 2,5,6-trisubstituted derivatives with acetobromoglucose with subsequent removal of the protective groups. The configuration of the glycoside center was proved on the basis of PMR spectral data.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 812–814, June, 1984.     

Synthesis and use of glycosyl phosphates as glycosyl donors

Differentially protected glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful glycosyl donors. Activation of beta-glycosyl phosphates by TMSOTf at -78 degrees C achieves the selective formation of beta-glycosidic linkages in excellent yields with complete stereoselectivity. Reaction with thiols results in the conversion of glycosyl phosphates into thioglycosides in nearly quantitative yield. An orthogonal coupling strategy using glycosyl phosphate donors and thioethyl glycoside acceptors allows for the rapid synthesis of a trisaccharide.     

Heterocyclic Analogs of 5,12-Naphthacenequinone. 1. Synthesis of Heterocyclic Analogs Starting from 2,3-Diaminoquinizarine

The amination of 2-nitroquinizarine using hydroxylamine gives 2-amino-3-nitroquinizarine, which, upon reduction, gives previously unreported 2,3-diaminoquinizarine, a key intermediate in the synthesis of heterocyclic analogs of 5,12-naphthacenequinone, namely, 4,11-dihydroxyanthra[2,3-d]imidazole-5,10-dione (imidazoloquinizarine), 4,11-dihydroxyanthra[2,3-d][1,2,3]triazole-5,10-dione (triazoloquinizarine), and 5,12-dihydroxynaphtho[2,3-g]quinoxaline-6,11-dione (pyrazinoquinizarine). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1081–1088, July, 2005.     

Synthesis of glycosyl isocyanides

Substitution of benzylated or methylated glycopyranosyl and furanosyl bromides with silver cyanide gives rise to glycosylisocyanides as main products. The isocyanide structure is ascertained by physical (¹³C NMR, IR) and by chemical methods (hydrolysis, isomerisation to nitriles).     

Synthesis of glycosyl dipyrromethanes

Treatment of peracetylated sugar trichloroacetimidates with dipyrromethane in the presence of boron trifluoride diethyl etherate gave peracetylated glycosyl dipyrromethanes in good yields. Regio- and stereo-selectivity of the glycosylation reactions were established.     

Synthesis and properties of diacetylene azides

A three-stage method was developed for the synthesis of diacetylene azides from diacetylene alcohols prepared by Cadiot-Chodkiewicz reaction. By their bromination the corresponding diacetylene bromides were obtained whose azidation resulted in the target diacetylene azides. The attempt was performed to prepare azides of triacetylene series, but the low stability of the synthesized triacetylene alcohols prevented their conversion into the corresponding bromides.     

Synthesis of aryl azides and vinyl azides via proline-promoted CuI-catalyzed coupling reactions

The coupling reaction of aryl halides or vinyl iodide with sodium azide under catalysis of CuI/L-proline works at relatively low temperature to provide aryl azides or vinyl azides in good to excellent yields.     

新型取代苯甲胺葡萄糖氮苷的合成及其抗缺氧活性

以取代苯甲醛(1a~1s)为原料,通过三条路线［A:1a~1o为起始原料,经硼氢化钠还原和溴代反应制得苄基溴衍生物(3a~3o); 3a~3f与邻苯丁二酰亚胺经Gabriel反应制得N-苯甲基邻苯丁二酰亚胺衍生物(4a~4f); 4a~4f与水合肼反应后与D-吡喃葡萄糖反应合成了N-β-D吡喃葡萄糖苯甲胺类化合物(6a~6f)。 B: 3g~3o与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5g~5o; 5g~5o在MeONa-MeOH中脱除乙酰基合成了6g~6o。 C: 1p~1s与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5p~5s; 5p~5s经MeONa-MeOH脱除乙酰基合成了6p~6s］合成了19个取代苯甲胺N-β-D吡喃葡萄糖氮苷类似物(6a~6s,其中6a, 6b, 6e, 6f, 6j, 6n~6q, 6s为新化合物),其结构经¹H NMR和ESI-MS表征。采用MTT法研究了6a~6s对缺氧内皮细胞代谢活力的影响。结果表明： 6a, 6g, 6h和6l的抗缺氧活性优于红景天苷。