P-38 亜鉛塩触媒グリコシル化反応の開発とアリスロバシリンの全合成(ポスター発表の部)

抄録

Although a large number of glycosylation procedures have been reported, leaving groups at anomeric centers are usually activated by a stoichiometric amount of reagent. We found that the common glycosylation donor, glycosyl chloride, is effectively activated by a catalytic amount of zinc salt. Thus we describe herein zinc salt catalyzed rhamnosylation, glucosylation and galactosylation of a variety of alcohols. For example the reaction of cholesterol (2) and L-rhamnosyl chloride 1 in the presence of 0.1 equiv of Zn(acac)_2 in dichloromethane at room temperature for 3h afforded α-rhamnoside 3 in 95% yield with complete stereoselectivity. The new catalytic glycosylation was applied for the total synthesis of a unique cyclic glycolipid, arthrobacilin A (4), isolated from Arthrobactor sp. NR2967. The chiral β-hydroxyester 13 was prepared by Noyori's BINAP-Ru catalyzed asymmetric hydrogenation of β-ketoester. Glycosylation of 13 with galactosyl chloride 14 in the presence of 0.1 equiv of zinc p-tert-butylbenzoate (15) and 22 equiv of acid scavenger, 2-methyl-2-butene, provide β-galactoside in 73% yield selectively. Condensation/cyclization of ω-hydroxylic acid 16 was examined by using DCC/DMAP・HCl and the desired cyclic trimer was obtained in 38% yield. Deprotection by catalytic hydrogenation provided arthrobacilin A, and it was identified with natural product. Cytotoxicity of arthrobacilin A as well as synthetic arthrobacilin analogs against Hela as well as HL-60 were examined, and synthetic trimer showed same toxicity with natural product, and synthetic cyclic tetramer showed higher activity then natural product against Hela.