Synthesis of a Fusion‐Isomeric Cellobionoimidazole and Its Evaluation against the syn‐Protonating Glycosidase Cel7A

Abstract

The fusion-isomeric cellobinoimidazole 2, a potential inhibitor of the syn-protonating b-glycosidase Cel7A, was synthesised by Koenigs-Knorr glycosylation of the a-D-arabinopyranoside 32, followed by selective hydrolysis. Glycosylation of 32 with acetobromoglucose 6 proceeded with poor diastereoselectivity, giving the desired 1,3-linked b-D-disaccharide 35 as minor product, besides the major 1,3-linked a-D-disaccharide 36. Hg 2+ -Promoted glycosylation of 32 led predominantly to the 1,2-ortho ester 33. Sequential removal of the silyl, acetyl, and allyl groups of 35 led to a 45 : 55 equilibrium mixture 2 and the manno-configured isomer 39. Similarly, deprotection of 36 gave a mixture of the maltonoimidazole 42 and the manno-configured isomer 43. According to a known protocol, the glycosyl acceptor 32 was synthesised in eleven steps and an overall yield of 8 -13% from D [17]. The inhibitory inactivity may be due to the requirement of Cel7A for di-or oligosaccharide substrates, and/or to an unsuitable position of the glycosidic heteroatom. An appreciation of these factors requires the synthesis of at least a disaccharide analogue 2 of 1 [18]. As the isomeric cellobionoimidazole 3 [19] is a potent inhibitor of the anti-protonating b-glycosidase Cel5A of family 5, a comparison of the inhibitory activity of 2 and 3 promised to be meaningful. We decided to synthesise this fusion-isomeric cellobionoimidazole 2.

A facile method for the preparation of sugar orthoesters promoted by anhydrous sodium bicarbonate

“…½a , J = 9.5, 9.7), 5.17 (dd, 1H, J = 3.9, 9.9), 4.61 (dd, 1H, J = 3.1, 3.5), 4.33 (dd, 1H, J = 5.5, 11.1), 4.28 (dd, 1H, J = 2.7, 11.0), 3.78 (m, 1H), 3.59-3.50 (m, 2H), 3.05 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H), 1.73 (s, 3H), 1.18 (t, 3H, J = 7.0). 13 …”

“…½a , 1H), 3.05 (s, 3H), 2.38 (t, 1H, J = 1.9), 2.12 (s, 3H), 2.08 (s, 3H), 1.77 (s, 3H). 13 C NMR (CDCl 3 ) d: 170.2, 169.6, 123.9, 97.6, 79.4, 76.0, 73.7, 71.8, 69.9, 67.2, 65.4, 51.1, 37.7, 24.0, 20.7 97.4, 75.5, 71.7, 70.1, 67.4, 66.6, 65.6, 37.7, 24.4, 23.7, 20.7 169.6, 137.4, 128.6, 128.4, 127.7, 127.5, 127.0, 124.2, 97.6, 76.0, 71.7, 70.0, 67.3, 65.5, 65.0, 37.7, 24.4, 20.7; HR-MS (ESI) anal. calcd for C 20 H 26 NaO 11 S [M + Na]: 497.1088; found: 497.1079.…”

“…At present, there are several methods in the literature for the preparation of carbohydrate 1,2-orthoesters. 10,11 The well-known method involves the treatment of peracetylated or perbenzoylated glycosyl bromides with alcohols in the presence of a quaternary ammonium salt 12 or silver triflate 5,13 and an organic base, usually syncollidine or 2,6-lutidine. 14 It is necessary to utilize two kinds of reagents, quaternary ammonium salt and bulky amine compound, for the reaction to occur.…”