Diastereoselectivity in the synthesis of D-glycero-D-aldoheptoses by 2-trimethylsilylthiazole homologation from hexodialdo-1,5-pyranose derivatives

Abstract

An exploration of the synthesis of D-glycero-D-altro-heptose, a constitutent of 0 antigen chains in lipopolysaccharides from Campylobacterjejuni serotypes 0:23 and 0:36 led to a study of the 2-trimethylsilylthiazole homologation procedure for heptose synthesis. In contrast to the diastereoselective formation of a 1,2:3,4-di-O-isopropylidene-~-glycero-~-heptopyranose derivative from 1,2:3,4-di-O-isopropylidene-a-~-galacto-hexodialdo-1,5-pyranose, methyl 2,3,4-tri-0-benzyl-D-hexodialdo-1,5-pyranosides with the gluco and manno configurations showed no preference for the formation of compounds with the D-glycero configuration. Attempts to achieve high diastereoselectivity in the conversion of L-glycero into the D-glycero isomers by oxidation at C-6 followed by reduction with L-selectride were unsuccessful with the thiazole adducts, but the desired products were formed in similar reactions of methyl 2,3,4-tri-0-benzyl-7-O-tert-butyldimethylsilyl-~-heptopyranosides. The approach to homologation in the altro series was thwarted by epirnerization at C-5 in the attempted formation of methyl 2,3,4-tri-O-benzyl-a-~-aItro-hexodialdo-1,5-pyranoside. ' The successful synthesis of methyl D-glycero-a-D-altro-heptopyranoside from methyl a-D-glucopyranoside was achieved by homologation followed by configurational alteration from the D-glrico to the D-altro series. NAVEEN K. KHARE, RAMEsH K. SOOD et GERALD 0. ASPINALL. Can. J. Chem. 72,237 (1994). (1). In view of the immunological importance of this region of LPS structure considerable attention has been directed to efficient methods for the preparation of derivatives of the sugar for incorporation into synthetic oligosaccharides (2-6). Methods of choice have been those involving a one-carbon extension from benzyl (1) or methyl (2) 2,3,4-tri-O-benzyl-a-~-manno-hexodialdo-1,5-pyranoside of which that involving reaction with (phenyldimethylsily1)magnesium chloride (4) proceeds with high diastereoselectivity to give derivatives of L-glycero-D-manno-heptose from which glycosides of the parent sugar may be readily obtained. In a recent study of the 0 antigen chains of LPSs of Campylobacter jejuni serotypes 0:23 and 0:36 unusual heptose sugars were found as four variants with the same configurationally unusual altro ring configuration (7). LPS preparations all contained trisaccharide,

Stereoselective Glycal Fluorophosphorylation: Synthesis of ADP‐2‐fluoroheptose, an Inhibitor of the LPS Biosynthesis

“…The combined organic layers were washed with saturated aqueous solution of NaHCO 3 then brine, dried over MgSO 4 , and concentrated in vacuo. The residue was purified by silica gel chromatography (cyclohexane/ethyl acetate 5:1) to furnish intermediate silyl ether 8 [37] as a colorless syrup (224 mg, 91 %). Trifluoromethanesulfonic anhydride (188 mL, 1.15 mmol) was added dropwise to a solution of silyl ether 8 (234 mg, 0.384 mmol) in pyridine (10 mL) at À40 8C, then the reaction mixture was allowed to warm to 0 8C and stirred for 1 h. After concentration in vacuo, the residue was subjected to chromatography on silica gel (cyclohexane/ethyl acetate 5:1), and all the fractions were successively concentrated and dried in vacuo.…”

Current methods for the synthesis of 2-substituted azoles

“…Scheme 106 depicts several aldehydes and the diastereomeric ratio obtained for recent examples which utilized 2-TST. [197][198][199][200][201][202][203] Dondoni has also demonstrated the use of 2-TST for the addition to fluorinated aryl and alkyl ketones (Scheme 107). 204 Acetophenones and other ketones have not been successful as electrophiles for 2-TST.…”

Syntheses of methyl glycosides of 6-deoxyheptoses

“…Hydrolysis of a sample of methyl glycoside 4 followed by reduction and acetylation furnished the 6-deoxyheptitol hexaacetate, which was indistinguishable by gas-liqud chromatography (glc) from the component in the C. jejuni serotypes 0:23 and 0:36 polysaccharide hydrolyzates (3). In identical manner methyl 2,3,4-tri-0-benzyl-or-D-mannopyranoside (6) (6) was converted successively into the 6-deoxyheptosidurononitrile (7), methyl 2,3,4-tri-0-benzyl-6-deoxy-or-D-manno-heptopyranoside (8), the parent methyl glycoside (9), and for further characterization the tetra-0-acetyl derivative (10) of 9. The previously prepared (6) methyl 6-deoxy-a-D-manno-heptopyranoside (8) served as a convenient starting material for the synthesis of the C-4 epimer with the talo configuration.…”

“…Unless otherwise stated, experimental methods and spectroscopic analyses were performed as described in the previous paper (9).…”

“…We describe here an alternative approach with the cyanide displacement of 2,3,4-tri-0-benzyl-a-~-glycopyranoside 6-sulfonate esters used by Baer et al (8) in the preparation of 6-deoxy-D-gluco-heptopyranosidurononitriles, followed by a two-step reduction involving treatment with diisobutylaluminum hydride (DIBAH), hydrolysis of the resulting imine, and further reduction with sodium borohydride. In the event this proved to be a fortunate choice for the synthesis of the altro derivative since, as reported in the accompanying paper (9), the attempted formation of the a-D-altro-hexodialdo-15-pyranoside by oxidation of methyl 2,3,4-tri-0-benzyla-D-altropyranoside (1) (10) was accompanied by configurational inversion at C-5 with the formation of the corresponding P-L-galacto derivative as the major product.…”