Jiri J. Krepinsky

Silver Trifluoromethanesulfonate(Triflate) Activation of Trichloroacetimidates in Glycosylation Reactions

Abstract Chemical syntheses of biologically active oligosaccharides, glycolipids and glycopeptides requires efficient stereospecific glycosylation reactions.2 One of the most effective glycosylation methods involves activation of anomeric imidates, particularly mchloroacetimidates, by Lewis acids such as boron trifluoride etherate (BF3·OEt2), mmethylsilyl mfluoromethanesulfonate (TMSOTF)3 and mfluoromethanesulfonic anhydride.4 In a recent example from this laboratory, BF3·OEt2, has been used to promote the glycosylation of methyl 2,3,6-tri-O-benzoyl-B-D-galactopyranoside (I)5 with 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-B-D-galactopyranosyl mchloroacetimidate (I): see Scheme 1. The expected β1-4-linked disaccharide III was obtained in 40% yield. The yield was so low since both the α-anomer and a 1-3-linked disaccharide were formed as by products, the latter in particularly large quantities (cf. Ref.7). The 1-3 disaccharide could be formed from a product of acid-catalyzed 3,4-migration of the benzoyl grou...

Syntheses of model oligosaccharides of biological significance.Synthesis of methyl 3,6-DI-O-(α-d-mannopyranosyl)-α-d-mannopyranoside and the corresponding mannobiosides

Abstract Methyl 2- O -allyl-4,6- O -benzylidene-3- O -(2,3,4,6-tetra- O -acetyl- α - d -mannopyranosyl)- α - d -mannopyranoside( 12 ) was prepared in 90 % yield by Helferich glycosylation of methyl 2- O -allyl-4,6- O -benzylidene- α - d -mannopyranoside ( 9 ) with tetra- O -acetyl- α - d -mannopyranosyl bromide ( 11 ). Removal of the benzylidene group and second Helferich glycosylation with 11 led to methyl 2- O -allyl-3,6-di- O -(2,3,4,6-tetra- O -acetyl- α - d -mannopyranosyl)- α - d -mannopyranoside ( 14 ) which, after deallylation and Zemplen deacetylation, gave the title compound 5. The disaccharides methyl 3- O -( α - d -mannopyranosyl)- α - d -mannopyranoside ( 7 ) and methyl 6- O -( α - d -mannopyranosyl)- α - d -mannopyranoside ( 6 ) have also been synthesized. Complete assignments of the 1 H-n.m.r. spectra of the compounds 5, 6 , and 7 are given.

Characterization of cytotoxic steroids in human faeces and their putative role in the etiology of human colonic cancer

It has been shown previously that chemically induced nuclear abeerrations in the murine colon are correlated with the carcinogenicity of the respective chemicals. Consequently, the nuclear aberration assay was utilized for the identification of putatife carcinogens in human faeces. Human fecal samples were fractionated by several chromatographic methods, and the assay led to the isolation of two substances. A combination of spectroscopic (mass, nuclear magnetic resonance, ultraviolet, and infrared) and chromatographic (HPLC and GLC) methods showed that they are 5-alpha- cholestan-3-one (I) and cholest-4-en-3-one (II). A number of C-27-C-30 steroids isolated from closely related fractions of feces were inactive in this assay. Thus I and II could play a role in etiology of large bowel cancer in humans.

On distribution of different fecapentaenes, the fecal mutagens, in the human population

It has been shown by an HPLC analysis using a quarternary solvent mixture in an isocratic mode that human excretors of these fecal mutagens excrete both fecapentaene -12 and -14 but the ratios vary greatly between individuals. Since these mutagens are produced by the bacterial flora of the colon, this may indicate differences in the flora between these individuals or differences in the availability of different precursor molecules in their colons. Any relationship of these findings to the etiology of colonic cancer is not clear.

Polymer-supported syntheses of oligosaccharides: Using dibutylboron triflate to promote glycosylations with glycosyl trichloroacetimidates

Abstract Dibutylboron triflate as a promoter of glycosylations with glycosyl trichloroacetimidates compares favourably with most other promoters.

A glycosylation reaction: conversion of methyl glycosides to glycosyl chlorides by boron trichloride

Abstract Methyl glycosides react readily with boron trichloride in dichloromethane solutions at −78 °C to give the corresponding glycosyl chlorides for subsequent use in glycosylation reactions. This reaction is compatible with the presence of glycosyl linkages in the molecule, as well as benzyl and acetyl protecting groups.

The effect of fecapentaenes on nuclear aberrations in murine colonic epithelial cells

Fecapentaenes, human fecal mutagens of bacterial origin, were intrarectally administered to mice in suppository form. Despite the strong, positive mutagenic response of fecanpentaenes using Ames tester strains TA 98 and TA 100, no increase in nuclear aberrations, taken as a measure of genotoxicity in colonic epithelial cells, was observed over control levels. In fecapentaene treated animals, however, the incidence of mitotic figures was increased above control levels to values comparable to those observed in mice treated with the known colon carcinogen, N-ethyl-N-nitrosourea. Thus, it would appear that fecapentaenes are not cytotoxic to murine colonic epithelia as judged by the nuclear aberration assay.

Metathesis of oligosaccharides. Relative stabilities of activated and deactivated glycosides of polyethylene glycol.

Abstract The preparation of glycosides and orthoesters of the monomethylether of polyethyleneglycol are described. The attempted glycosylation of these glycosides unexpectedly led to glycosyl exchange instead of the expected oligosaccharides. This observation suggests that PEG as aglycon acts both as a leaving group and a nucleophile. A hypothesis explaining metathesis of oligosaccharides under glycosylation conditions has been formulated.

Complete Assignment of the 360 MHz 1H NMR Spectra of Some Oligomannosides

Abstract The 360 MHz 1H NMR spectra of four closely related synthetic oligomannosides have been completely assigned. This was achieved by a combination of spin-tickling difference spectroscopy and spectral simulation. The compounds are: methyl 3-0-(α-D-mannopyranosyl)-α-D-mannopyranoside (II3), methyl 6-0-(α-D-mannopyranosyl) -α-D-mannopyranoside (II6), methyl 3,6-di-0-(α-D-mannopyranosyl) -α-D mannopyranoside (III) and methyl 3-0-(α-D-mannopyranosyl)-6-0-(3-0-α-D-manno-pyranosyl-α-D-mannopyranosyl)-α-D-mannopyranoside (IV). These oligomannosides are analogues of the high mannose structures occurring naturally in the N-linked glycopeptides of glycoproteins. A number of long range chemical shift perturbations were observed which are interpreted as being of methyl mannotrioside, methyl 3,6-di-0-(α-D-mannopyranosyl)-α-D-mannopyranoside (III); the related disaccharides, methyl 6-0-(α-D-mannopyranosyl)-α-D-mannopyranoside (II6) and methyl 3-0-(α-D-mannopyranosyl)-α-D-mannopyranoside (II3); and a tetrasaccharid...

A CONVENIENT SYNTHESIS OF PER-O-METHYLATED 6-O-MONOSUBSTITUTED BETA -CYCLODEXTRINS

Cyclodextrins are cyclic oligosaccharides that function as chiral host molecules exhibiting enantioselectivity in reactions with racemic guests1 and thus they represent a significant moiety of artificial enzymes.2 The most easily obtainable and relatively inexpensive are s-cyclodextrins (s-CD), cyclic heptaglucosides in which glucopyranosyl residues are linked by an α(1-4) glycosidic bonds. s-CD is surprisingly poorly soluble in water (1.8 g in 100 mL)3 but the solubility of its derivatives is often significantly better. For instance, s-CD with all secondary hydroxyls methylated, forms 50% aqueous solutions at room temperature,4 and even completely methylated s-CD is ten times more soluble in water (17 g in 100 mL)5 than s-CD itself. Methylation also alters the binding of the substrates to s-CD often increasing its specificity and strength,6 and renders the hydroxyl groups unreactive. Therefore, it is of interest to prepare derivatives of s-CD in which the enzyme-mimicking group is bound to one hydroxyl (...