Oligosaccharide analogues of polysaccharides - Part 22 - Synthesis of cyclodextrin analogues containing a buta-1,3-diyne-1,4-diyl or a butane-1,4-diyl unit

The peracetylated hexaamylose (maltohexaose) 18 was obtained by an improved acetolysis of cyclomaltohexaose (a-cyclodextrin, alpha -CD, 16), and trans formed into the benzyl- and 4-chlorobenzyl-protected thioglycosides 22 and 23, respectively (Scheme 2). Sequential chain elongation of 22 and 23 by gl ycosidation of the C-ethynylated glucosides 9 and 11 gave the alpha -anomer ic heptaglycosides 24 and 26, respectively, and their anomers 25 and 27 (Sc heme 3). These were transformed into the glycosyl acceptors 28,30, and 3L G lycosidation of 28 and 30 by 13 and 15. respectively, led to the benzyl-pro tected octasaccharides 32 (alpha alpha (5)alpha) and 33 (beta alpha (5)alph a), and to the chlorobenzylated analogues 34 (alpha alpha (5)beta) and 35 ( beta alpha (5)alpha), while glycosidation of 31 led to the 4-chlorobenzyl-p rotected analogues 36 (alpha alpha (5)beta) and 37 (beta alpha (5)beta) (Sc heme 4). Hay coupling of O-Bn- and O-Ac-protected linear octaoses 32 (alpha alpha (5)alpha) and 33 (beta alpha (5)alpha) led to the cyclooctaamylose ( gamma -cyclodextrin) analogues 38 and 43, respectively (Scheme 5). Similarl y the 4-chlorobenzyl-protected analogues 34 and 35 gave 39 and 44, and the anomeric linear precursors 36 and 37 provided the cyclootaamylose analogues 48 and 50. respectively (Scheme 6). The influence of the constitution and configuration of the linear precursors on the rate and yield of the cyclisa tion was relatively weak. Deprotection and hydrogenation of 38 and 43 yield ed the gamma -CD analogues 42 (alpha alpha (5)alpha) and 47 (beta alpha (5) alpha), where one glycosidic O-atom is replaced by a butanediyl group. whil e FeCl3-promoted dechlorobenzylation of 39 and 44 did not affect the butadi yne moiety and afforded the acetyleno gamma -CD's 40 (alpha alpha (5)alpha) and 45 (beta alpha (5)alpha). respectively. Similarly, deprotection of 48 and 50 afforded the acetyleno gamma -CD analogues 49 (alpha alpha (5)beta) and 51 (beta alpha (5)beta), respectively, which contain one butanediyl moi ety instead of a glycosidic O-atom. MM3* Force-field calculations evidence the strong influence of the configuration and constitution of the new gamma -CD analogues on the shape of the cavity.