Thiazole-Based Synthesis of Formyl C-Glycosides

Abstract

A method for the installation of the formyl group at the anomeric position of pyranoses and furanoses starting from the corresponding lactones has been developed. The strategy involves the addition of 2-lithiothiazole to the sugar lactone, followed by the silane reduction of the acetylated resultant ketol and the unmasking of the formyl group from the thiazole ring. All steps have been studied in some details to improve chemical efficiency and stereochemical control. Hence, reversed :ß ratios of ketols were found in kinetic and thermodynamic mixtures, the former being consistent with a steric effect control of the substituents and the latter by the electronic effect of the ring oxygen. Seven sugar aldehydes with different D-pyranosidic (2,3,4,6-tetra-O-benzyl-gZuco, -galacto, and -manno, 2-azido-3,4,6-tri-0-benzyl-2-deoxy-goZacfo) and D-furanosidic moieties (5-O-benzyl-2,3-isopropylidene-nbo; 2,3,5-tri-O-benzyl-ribo; 2,3:5,6-di-0-isopropylidene-mozmo) were prepared in 52-65% isolated overall yield from the corresponding lactone.

The synthesis of d-C-mannopyranosides

“…The introduction of a thiazole in the anomeric position of a mannosyl lactone, followed by deoxygenation of the resulting ketal to give the corresponding b-C-mannopyranoside was first reported by Dondoni and Scherrmann in 1994 (Scheme 53) [192].…”

Novel nicotinamide adenine dinucleotide analogues as selective inhibitors of NAD+-dependent enzymes

“…15,16 (Scheme 1) The thiophene-3 (and -2)-carbonitrile 2a (and 2b), treated with LDA in THF, were reacted with lactone 3 for 30 min at 278 8C to form the lactol. Quenching of the reaction at 278 8C by addition of a solution of saturated NH 4 Cl allowed the isolation of the hemiketals 4a and 4b as single isomers.…”

“…The chemical instability of similar carbohydrates towards such reaction conditions had been previously observed. 16,17 Townsend had reported a procedure involving an acetylated hemiketal intermediate prepared in situ by trapping of the Scheme 1. Synthesis of carbonitrile thiophene C-nucleoside analogues.…”

“…16 Yet, Benhinda recognised that the condensation step was very sensitive to steric factors imposed by the incoming nucleophile, 17 which could explain the results described by Townsend. However, the nucleophile employed in the study by Dondoni, a thiazolyl anion, is isosteric to the thiophene-3 (and -2) -carbonitrile 2a (and 2b) used in the present study.…”

Synthesis and Use of Tetrahydrofuran- and Tetrahydropyran-Amino Acids

“…Dondoni et al developed a route from lactones of type 28 to THP-α-amino acids 29 (scheme 4) [14,15].…”