Direct chemical synthesis of the beta-D-mannans: the beta-(1-->2) and beta-(1-->4) series

The direct syntheses of a beta-(1-->2)-mannooctaose and of a beta-(1-->4)-mannohexaose are reported by means of 4,6-O-benzylidene-protected beta-mannosyl donors. The synthesis of the (1-->2)-mannan was achieved by means of the sulfoxide coupling protocol, whereas the (1-->4)-mannan was prepared using the analogous thioglycoside/sulfinamide methodology. In the synthesis of the (1-->4)-mannan, the glycosylation yields and stereoselectivities remain approximately constant with increasing chain length, whereas those for the (1-->2)-mannan consist of two groups with the formation of the tetra- and higher saccharides giving yields and selectivities consistently lower than those of the lower homologues. The decrease in yield after the trisaccharide in the (1-->2)-mannan synthesis is attributed to steric interference by the n-3 residue and is consistent with the collapsed, disordered structure predicted by early computational work. The consistently high yields and selectivities seen in the synthesis of the (1-->4)-mannan are congruent with the more open, ordered structure originally predicted for this polymer. The lack of order in the structure of the (1-->2)-mannan, as compared to the high degree of order in the (1-->4)-mannan, is also evident from a comparison of the NMR spectra of the two polymers and even from their physical nature: the (1-->2)-mannan is a gum and the (1-->4)-mannan is a high melting solid.     

A general method for the synthesis of 2-arylpyrroles

Reaction of methyl azidoacetate with β-arylacroleins, followed by cyclisation of the obtained derivatives easily leads to arylpyrroles. N M R and mass spectra data are given and the Vilsmeier formylation of some arylpyrroles is described.     

N-trifluoroacetyl sialyl phosphite donors for the synthesis of alpha(2 --> 9) oligosialic acids

[reaction: see text] A new method for the synthesis of alpha(2 --> 9) oligosialic acids is developed using phosphite sialyl donors that are protected with a C-5 N-trifluoroacetyl (NHTFA) substituent. Compared with conventional donors, these donors gave a higher degree of alpha-anomeric selectivity during glycosidic bond formation and better yields during iterative sialylation in the synthesis of oligosialic acids.     

A general and convenient method for the synthesis of unesterified carbamoyl- and thiocarbamoyl-phosphonic acids

Unesterified carbamoyl- and thiocarbamoyl-phosphonic acids were prepared in high yields by the reaction of tris(trimethylsilyl) phosphite with isocyanates and isothiocyanates followed by treatment of the 1:1 carbonyl adducts with aniline-containing methanol.     

A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction

We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.     

An efficient method for the preparation of glycosides with a free C-2 hydroxyl group from thioglycosides

A new and efficient method to produce glycosides with a free C-2 hydroxyl group through 1,2-acyl group migration which occurs during the hydrolysis of 4,6-benzylidene protected thioglycosides has been developed. The acyl transfer products allow for further elaboration.     

A Julia olefination approach to the synthesis of functionalized enol ethers and their transformation into carbohydrate-derived spiroketals

A synthesis of spiroketals from carbohydrate lactones is reported. A modified Julia olefination is used to synthesize trisubstituted and highly functionalized exo-glycals, which were subsequently transformed into spiroketals under acidic conditions.     

A mild method for the synthesis of 2-ketopyrroles from carboxylic acids

A mild method for the synthesis of 2-ketopyrroles from carboxylic acids via 2-pyridylthiolesters and pyrrylmagnesium chloride is described.     

A new method for the synthesis of α-arylalkanoic acids by the use of 1,2-rearrangement of the aryl group

A simple synthetic method of α-arylalkanoic acids was accomplished by the use of a novel 1,2-rearrangement of the aryl group and this method was applied to the syntheses of some biologically important substances.     

A general method for the preparation of 2-substituted-4-oxo-3-quinolinecarboxylic acids

A general method for preparing 2-substituted-4-oxo-3-quinolinecarboxylic acids and 2-substituted-4-oxo-1,8-naphthyridine-3-carboxylic acids as new analogs in the quinolone class of antiinfectives has been developed. The reaction of a Grignard reagent in the presence of copper(I) iodide with the 4-oxo-3-quinolinecar-boxylic acid esters and 4-oxo-1,8-naphthyridine-3-carboxylic acid esters yields the desired 2-substituent. Re-introduction of the 2,3-double bond is effected by phenylselenation of the 3-position, oxidation to the selen-oxide, and in situ syn-elimisation. Depending on the degree of steric crowding between the 2-substituent and the 3-carboxylic acid group, hydrolysis of the ester to the carboxylic acid could be carried out under acidic or basic conditions.     

A mild and general method for the synthesis of 2-substituted-5-hydroxypyrimidines

5-Bromopyrimidines are converted to 5-hydroxypyrimidines using a mild synthetic procedure. The method is general and can be applied to compounds containing functional groups which are not compatible with the other reagents previously available for this conversion.     

Synthesis of thio-linked disaccharides by 1-->2 intramolecular thioglycosyl migration: oxacarbenium versus episulfonium ion intermediates

The conversion of 1,1'-thio-linked glucopyranosyl alpha-D-mannopyranosides to 1,2-thio-linked methyl sophorosides or methyl kojibiosides is described. The method involves the 1-->2-migration of the thioglucopyranosyl portion of the nonreducing disaccharide with inversion of configuration at C-2 of the mannopyranose ring and concomitant formation of the methyl glucopyranoside. The thioglucosyl migration does not occur when electron-withdrawing benzoate protecting groups are present. The rearrangement occurs with retention of configuration in the migrating thioglucoside but the methyl glycoside is formed as a mixture of alpha- and beta-isomers. This is attributed to a mechanism involving an oxacarbenium-ion intermediate rather than an episulfonium-ion intermediate. The relevance of this work to recent theoretical predictions concerning the relative stability of such intermediates is discussed.     

A novel, general method for the synthesis of nitrile oxides: dehydration of O-silylated hydroxamic acids

[reaction: see text] O-Silylated hydroxamic acids serve as stable, readily accessible, crystalline precursors to nitrile oxides when treated with trifluoromethanesulfonic anhydride and triethylamine. Under these mild conditions in the presence of olefins O-silylated hydroxamic acids afford isoxazoline cycloadducts. This procedure represents a novel, general method for the one-step generation of nitrile oxides, which complements existing protocols.     

The synthesis of 2-(alkylthio)- and 2-(arylthio)-3-cyanothiophenes. The nucleophilic displacement of the alkylsulfinyl group by thiols.

The nucleophilic substitution of activated 2-(alkylsulfinyl)thiophenes with alkyl- or arylmercaptans gives the corresponding 2-(alkylthio)- or 2-(arylthio)- substituted thiophenes. When thiolate anion is used instead of thiol, sulfoxide reduction is the main reaction.     

Allyloxy and propargyloxy group migration: role of remote group participation in the synthesis of 5-C-nucleosides and other sugar derivatives

In 1-deoxy-xylofuranose derivatives possessing a good leaving group at 2-C, participation of allyloxy and propargyloxy substituents at 5-C results in loss of the 2-C substituent and attack of various nucleophiles at 5-C of the oxonium intermediate. Such participation of a benzyloxy or crotyloxy group leads to dioxabicyclo[2.2.1]heptane rings.     

A new general, practical and enantioselective synthesis of α-amino acids

In recent years, considerable efforts have been expended to the development ofenantioselective synthesis of α-amino acids and the use of α-amino acids as chiralbuilding blocks for the synthesis of complex molecules. Numerous unnatural aminoacids which are often the characteristic units of biologically active peptides, have alsobeen discovered. Herein we describe a convenient and general access to natural andunnatural α-amino acids which are based on the use of the chiral building blocks,(S)-1a-e and (R)-1a-e from kinetic resolution of α-furfuryl amines (Scheme 1).