Recent developments in oligosaccharide synthesis: tactics,solid-phase synthesis and library synthesis

Oligosaccharides, commonly found on the cell surfaces, are deeply involved in a variety of important biological functions, yet demanding difficulties synthesizing such structures limit the investigation of their functions. Technologies to chemically synthesize these oligosaccharides have dramatically advanced during the last two decades mainly due to the introduction of good anomeric leaving groups. In addition, tactical analyses have been addressed to enhance the overall efficiency of oligosaccharide synthesis. Based on the advancement of solution-phase chemistry, solid-phase technologies are being investigated in connection with the current trend of combinatorial chemistry and high throughput screening. This review summarizes the necessary solution-phase methodologies, the status of solid-phase synthesis of oligosaccharides, and combinatorial synthesis of oligosaccharide libraries.     

Benzothiazines in synthesis. Formal synthesis of erogorgiaene

A benzothiazine, readily available in enantiomerically pure form via a completely selective, intramolecular addition of a sulfoximine-stabilized carbanion to an α,β-unsaturated ester, could be converted to a precursor to erogorgiaene in good overall yield.     

金属蒸气合成在金属有机合成中的应用

本文简要地介绍了金属蒸气合成法的基本原理、仪器和实验技术, 并按金属原子分别与炔、单烯、多烯、环烯、芳烃体系、卤代烃、有机混和物的反应及有机金属硼化合物的合成, 对金属蒸气合成法在金属有机合成中的应用进行了讨论。     

Total synthesis of apoptolidin: completion of the synthesis and analogue synthesis and evaluation

The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner-Wadsworth-Emmons coupling of fragments 22 and 25. The final stages of the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane 2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection. The developed synthetic technology was applied to the construction of several analogues including 74, 75, and 77 which exhibit significant bioactivity against tumor cells.     

Heterodiene synthesis

Transamination occurs in the reaction of amidines of benzoic and trichloro- and trifluoroacetic acids with azomethines obtained from aniline and various aromatic aldehydes; two molecules of the resulting benzylideneamidines react to give 1,2-dihydro-sym-triazines via the Diels-Alder scheme with the liberation of imino aldehydes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 281–283, February, 1973.See [1] for communication IV.     

Heterodiene synthesis

Both 1,4,-cycloaddition with the formation of a 1,4-dihydro-1,2,4-triazene derivative and electrophilic addition of acetyldicarboxylic acid ester to the secondary nitrogen atom occur during the reaction of acetylenedicarboxylic acid ester with 1,5-diphenyl-3-methyl-3-methylformazan. In the case of l,5.diphenylformazan, the reaction proceeds only in the second direction.See [3] for Communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1704–1705, December, 1970.     

Biology-oriented synthesis

Which compound classes are best suited as probes and tools for chemical biology research and as inspiration for medicinal chemistry programs? Chemical space is enormously large and cannot be exploited conclusively by means of synthesis efforts. Methods are required that allow one to identify and map the biologically relevant subspaces of vast chemical space, and serve as hypothesis‐generating tools for inspiring synthesis programs. Biology‐oriented synthesis builds on structural conservatism in the evolution of proteins and natural products. It employs a hierarchical classification of bioactive compounds according to structural relationships and type of bioactivity, and selects the scaffolds of bioactive molecule classes as starting points for the synthesis of compound collections with focused diversity. Navigation in chemical space is facilitated by Scaffold Hunter, an intuitively accessible and highly interactive software. Small molecules synthesized according to BIOS are enriched in bioactivity. They facilitate the analysis of complex biological phenomena by means of acute perturbation and may serve as novel starting points to inspire drug discovery programs.     

Heterodiene synthesis

2-Phenyl-4,6-diaryl-1,2-dihydro-sym-triazines react with hexafluoro-2-butyne as a dienophile to give 4,5-bis(trifluoromethyl)-2,6-diarylpyrimidines.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–123, January, 1977.     

Formal synthesis of nitidine through palladium-catalyzed isocoumarin synthesis

The isoquinolone intermediate 9 for the synthesis of nitidine was synthesized through palladium-catalyzed formation of isocoumarin 7 from o-styrylbenzoic acid derivative 5, which was prepared from palladium-catalyzed coupling reactions of aryl iodide 1 and 2 with vinylsilane.     

Asymmetric synthesis of cyclobutanones: synthesis of cyclobut-G

A simple, efficient, and stereoselective approach has been developed for obtaining chiral cis- and trans-disubstituted cyclobutanones from readily available alkyl- and functionalized alkyl-substituted enol ethers. The usefulness of these cyclobutanones is illustrated by an enantioselective synthesis of cyclobut-G (Lobucavir).     

Anion-templated synthesis

In contrast to the well-studied templating properties of cationic and neutral species there are relatively few examples of anion-templated syntheses. This is attributed to some of the intrinsic properties of anions such as their diffuse nature, pH sensitivity, and their relative high solvation free energies. However, the increasing number of anion-templated assemblies reported over the past few years demonstrates that these limitations are not as critical as first thought. This review summarizes the most important results on the use of anions as directing agents for the syntheses of a wide range of inorganic and organic assemblies (such as macrocycles, cages, helicates, rotaxanes, and extended structures). It is hoped that this will stimulate a closer look into this emerging area of supramolecular chemistry.     

Heterodiene synthesis

The reaction of trichloro- and trifluoroacetic acid amidines with aromatic aldehydes and the reaction of benzamidine with butyraldehyde yielded, respectively, 2-aryl-4,6,-bis(trichloromethyl)-, 2-aryl-4,6-bis(trifluoromethyl)-1,2-dihydro-sym-triazines, and 2-propyl-4,6-diphenyl-1, 2-dihydro-sym-triazine. The reactions of these compounds and the previously obtained sym-dihydrotriazines with acetylenedicarboxylic and propiolic acid esters were studied.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 704–707, May, 1971.     

Tellurium in organic synthesis: synthesis of bioactive butenolides

Reduction of (Z)-β-butyltelluro-enones gives the corresponding γ-hydroxy vinylic tellurides with retention of the double bond configuration. Reaction of γ-hydroxy vinylic tellurides with 2 equiv of n-butyllithium produces 1,4-C,O-dianions, which on reaction with carbon dioxide give the corresponding butenolides.     

Palladium mediated spiroketal synthesis: application to pheromone synthesis

Stereospecific Stille coupling reactions of 2-metallo-dihydropyrans with Z-vinyl iodo alcohols and subsequent cyclisation provides rapid access to 1,7-dioxaspiro[5.5]undecane family of spiroketals.     

Benzothiazines in synthesis. Toward the synthesis of pseudopteroxazole

[reaction: see text] The tricyclic benzothiazine 15 was prepared in a straightforward fashion via a completely stereoselective intramolecular Friedel-Crafts alkylation. This compound represents a potential precursor to the antitubercular agent, pseudopteroxazole. Its synthesis proceeded via a completely selective, intramolecular addition of a sulfoximine-stabilized carbanion to an alpha,beta-unsaturated ester, followed by functional group manipulations.     

Benzothiazines in synthesis. A total synthesis of pseudopteroxazole

An enantioselective total synthesis of the naturally occurring antitubercular agent pseudopteroxazole is described. The synthesis is organized around the use of a stereoselective, intramolecular addition of a sulfoximine carbanion to an alpha,beta-unsaturated ester to form an enantiomerically pure benzothiazine. Other important processes include a completely stereoselective intramolecular Friedel-Crafts alkylation and a stereoselective and regioselective hydrogenation. [structure: see text]