Oligosaccharide Analogues of Polysaccharides. Part 1. Concept and synthesis of monosaccharide‐derived monomers

Abstract

AbstractIt is proposed to study the influence of interresidue H‐bonds on the structure and properties of polysaccharides by comparing them to a series of systematically modified oligosaccharide analogues where some or all of the glycosidic O‐atoms are replaced by buta‐1,3‐diyne‐1,4‐diyl groups. This group is long enough to interrupt the interresidue H‐bonds, is chemically versatile, and allows a binomial synthesis. Several approaches to the simplest monomeric unit required to make analogues of cellulose are described. In the first approach, allyl α‐D‐galactopyranoside (1) was transformed via 2 and the tribenzyl ether 3 into the triflate 4 (Scheme 2). Substitution by cyanide (→ 5–7) followed by reduction with DIBAH led in high yield to the aldehyde 9, which was transformed into the dibromoalkene 10 and the alkyne 11 following the Corey‐Fuchs procedure (Scheme 3). The alkyne was deprotected via 12 or directly to the hemiacetal 13. Oxidation to the lactone 14, followed by addition of lithium (trimethylsilyl)acetylide Me3SiCCLi/CeCl3 (→ 15) and reductive dehydroxylation afforded the disilylated dialkyne 16. The large excess of Pd catalyst required for the transformation 11 → 13 was avoided by deallylating the dibromoalkene 10 (→ 17 → 18), followed by oxidation to the lactone 19, addition of Me3SiCCLi to the anomeric hemiketals 20 (α‐D/β‐D 7:2), dehydroxylation to 21, and elimination to the monosilylated dialkyne 22 (Scheme 3). In an alternative approach, treatment of the epoxide 24 (from 23) with Me3SiCCLi/Et2AlCl according to a known procedure gave not only the alkyne 27 but also 25, resulting from participation of the MeOCH2O group (Scheme 4). Using Me3Al instead of Et2AlCl increased the yield and selectivity. Deprotection of 27 (→ 28), dibenzylation (→ 29), and acetolysis led to the diacetate 30 which was partially deacetylated (→ 31) and oxidized to the lactone 32. Addition of Me3SiCCLi/TiCl4 afforded the anomeric hemiketals 33 (α‐D/β‐D 3:2) which were deoxygenated to the dialkyne 34. This synthesis of target monomers was shortened by treating the hydroxy acetal 36 (from 27) with (Me3SiCC)3Al (Scheme 5): formation of the alkyne 37 (70%) by fully retentive alkynylating acetal cleavage is rationalised by postulating a participation of HOC(3). The sequence was further improved by substituting the MeOCH2O by the (i‐Pr)3SiO group (Scheme 6); the epoxide 38 (from 23); yielded 85% of the alkyne 39 which was transformed, on the one hand, via 40 into the dibenzyl ether 29, and, on the other hand, after C‐desilylation (→ 41) into the dialkyne 42. Finally, combined alkynylating opening of the oxirane and the 1,3‐dioxolane rings of 38 with excess Et2Al CCSiMe3 led directly to the monomer 43 which is thus available in two steps and 77% yield from 23 (Scheme 6).