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

Abstract

Dedicated to Edgar Heilbronner on the occasion of his 80th birthdayThe peracetylated hexaamylose (maltohexaose) 18 was obtained by an improved acetolysis of cyclomaltohexaose (a-cyclodextrin, a-CD, 16), and transformed into the benzyl-and 4-chlorobenzyl-protected thioglycosides 22 and 23, respectively (Scheme 2). Sequential chain elongation of 22 and 23 by glycosidation of the C-ethynylated glucosides 9 and 11 gave the a-anomeric heptaglycosides 24 and 26, respectively, and their anomers 25 and 27 (Scheme 3). These were transformed into the glycosyl acceptors 28, 30, and 31. Glycosidation of 28 and 30 by 13 and 15, respectively, led to the benzyl-protected octasaccharides 32 (aa 5 a) and 33 (ba 5 a), and to the chlorobenzylated analogues 34 (aa 5 a) and 35 (ba 5 a), while glycosidation of 31 led to the 4-chlorobenzylprotected analogues 36 (aa 5 b) and 37 (ba 5 b) (Scheme 4). Hay coupling of O-Bn-and O-Ac-protected linear octaoses 32 (aa 5 a) and 33 (ba 5 a) led to the cyclooctaamylose (g-cyclodextrin) analogues 38 and 43, respectively (Scheme 5). Similarly, 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 cyclisation was relatively weak. Deprotection and hydrogenation of 38 and 43 yielded the g-CD analogues 42 (aa 5 a) and 47 (ba 5 a), where one glycosidic O-atom is replaced by a butanediyl group, while FeCl 3 -promoted dechlorobenzylation of 39 and 44 did not affect the butadiyne moiety and afforded the acetyleno g-CDs 40 (aa 5 a) and 45 (ba 5 a), respectively. Similarly, deprotection of 48 and 50 afforded the acetyleno g-CD analogues 49 (aa 5 b) and 51 (ba 5 b), respectively, which contain one butanediyl moiety instead of a glycosidic O-atom. MM3* Force-field calculations evidence the strong influence of the configuration and constitution of the new g-CD analogues on the shape of the cavity.

Electrospray ionization mass spectrometry: a key analytical tool for the characterization of regioselectively derivatized maltooligosaccharides obtained starting from natural β‐cyclodextrin

“…In spite of this, there has been relatively little published work to date to reflect such demands due to the difficulties in achieving good regioselectivity by chemical modification of linear oligosaccharides and in accessing pure homologous linear oligosaccharides on a large scale. Nevertheless, it is known that maltooligosaccharides (linear oligosaccharides constituted of glucose monomer molecules α (1 → 4) linked) with a degree of polymerization (DP) from 6 to 8 can be obtained readily by acetolysis of esterified α ‐, β ‐ and γ ‐cyclomaltooligosaccharides (cyclodextrins, CDs) under H 2 SO 4 catalysis (Kuzuhara's method5, 6) or under HClO 4 catalysis (Vasella's method7). We have recently adapted these procedures8 to synthesize regioselectively C‐6‐derivatized maltoheptaoses (DP7) 4 to 10 in high purity and yield, starting from natural β ‐CD (Scheme ).…”

Nitrogen-Containing Macrocycles Having a Carbohydrate Scaffold

“…168 Cleavage of the peracetate (322) of α-CD under acetolysis conditions (70% HClO 4 -Ac 2 O) provided maltohexaose peracetate 323 (α:β ¼ 9:1), which was converted into the phenyl 1-thioglycoside 324 according to Hanessian's method. 168 Cleavage of the peracetate (322) of α-CD under acetolysis conditions (70% HClO 4 -Ac 2 O) provided maltohexaose peracetate 323 (α:β ¼ 9:1), which was converted into the phenyl 1-thioglycoside 324 according to Hanessian's method.…”

“…168 Cleavage of the peracetate (322) of α-CD under acetolysis conditions (70% HClO 4 -Ac 2 O) provided maltohexaose peracetate 323 (α:β ¼ 9:1), which was converted into the phenyl 1-thioglycoside 324 according to Hanessian's method. 171 Reductive opening of the benzylidene acetal ring in maltohexaose derivative 327 yielded the secondary alcohol 328. 171 Reductive opening of the benzylidene acetal ring in maltohexaose derivative 327 yielded the secondary alcohol 328.…”

“…169 Following O-deacetylation of 324, the resulting thioglycoside 325 was treated with α,α-dibromotoluene according to the method of Garegg and Swahn 170 to yield the 4 VI ,6 VI -O-benzylidene derivative 326, which was then 4-chlorobenzylated to afford the fully protected derivative 327 (Scheme 57). 168 Slightly different methodology for the synthesis of cyclodextrin analogues containing 1,2,3-triazole units was proposed by Gin and coworkers, who synthesized highly symmetrical macrocycles starting from the azido-acetylene 337, prepared from p-methoxyphenyl 2,3,6-tri-O-benzyl-α-D-mannopyranoside (335) in a number of well-defined steps. The free hydroxyl group in 328 was alkylated with propargyl bromide, and the corresponding propargyl ether was glycosylated with 2-chloroethanol to provide compound 329 as a mixture of anomers (85%; α:β ¼ 9:1).…”

Recent Uses of Iron (III) Chloride in Organic Synthesis

“…Several groups have used FeCl 3 to debenzylate or anomerize carbohydrates by following the method developed by Nakanishi et al [101]. Vasella and co-workers have used FeCl 3 as a debenzylation reagent, [102] in the synthesis of cyclodextrin analogues containing a buta-1,3-diyne-1,4-diyl.…”