2-C-Alkynyl and 2-C-cis-Alkenyl β-Mannosides with Acetal Protected γ-Aldehyde Functionality via 2-Uloside Alkynylation and Lindlar Hydrogenation

Abstract

Abstract:Benzyl 3,4,6-tri-O-benzyl-β-D-arabino-hexos-2-ulo-1,5-pyranoside was subjected to mannoselective ketone alkynylation with propiolaldehyde dibenzyl acetal, resulting in the formation of a 2-C-alkynyl β-mannoside bearing a γ-dibenzyl acetal functionality. Subsequent transacetalization of the acetal moiety with methanol and 1,3-dihydroxypropane and acetylation of position 2, respectively, gave 4 different 2-C-alkynyl branched mannosides. Lindlar hydrogenation of the latter under optimized conditions in dimethylformamide afforded a series of 2-C-cis-alkenyl mannosides. X-ray molecular structures of benzyl 3,4,6-tri-O-benzyl-β-D-arabino-hexos-2-ulo-1,5-pyranoside and of the branched glycoside benzyl 3,4,6-tri-O-benzyl-2-C-((Z)-3,3-dibenzyloxyprop-1-en-1-yl)-β-Dmannopyranoside are reported.

Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

“…Initially, we developed a synthetic strategy towards B based on key intermediate E (Figure , bottom), which was, after dihydroxylation of the side chain alkene and global deprotection, anticipated to form the acetal‐hemiacetals B . However, several dihydroxylation methods did not afford the desired side chain diol.…”

“…Key steps of the retrosynthetic analysis for the target bicyclic hemiacetals B via alkenes C and alkynes D (top), and previously published, unsuitable substrates E (bottom) . R/R′ = protecting groups.…”

“…Accordingly, to examine the suitability of diverse protecting groups, benzylated 2‐uloside 1 ,, available from d ‐glucose in six steps, was subjected to alkynylation reactions with a set of alkynes including unprotected propargyl alcohol, TIPS‐protected and THP‐protected propargyl alcohol (Scheme ). The addition of free propargyl alcohol was achieved using excessive ethylmagnesium bromide as the base in THF .…”

“…However, 2a was obtained in only mediocre yields. For the synthesis of 2b / 2c , a protocol using n ‐butyllithium as the base in THF at –80 °C was applied …”

“…The mixture was heated to 80 °C for 1.5 h and then cooled to ambient temperature. Next, this solution was added dropwise to benzyl 3,4,6‐tri‐ O ‐benzyl‐β‐ d ‐ arabino ‐hexopyranoside‐2‐ulose 1 , (0.20 g; 0.37 mmol) in anhydrous THF (5 mL) at room temperature with a programmable syringe pump (addition rate: 0.12 mL/min). The reaction mixture was stirred for another 30 min, when TLC control (toluene/ethyl acetate, 4:1) showed complete consumption of the starting material.…”