具有抗肿瘤活性的寡糖β-D-葡萄糖-(1→3)-[β-D-葡萄糖-(1→6)]-β-D-葡萄糖-(1→3)-β-D-葡萄糖-(1→6)-[β-D-半乳糖-(1→4)-β-D-葡萄糖-(1→3)]-β-D-葡萄糖月桂酯的合成

Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity.

作者信息

Mei Xiangdong, Heng Linsen, Fu Mingkun, Li Zhimin, Ning Jun

机构信息

College of Bio-information, Chongqing University of Post and Telecommunications, Chongqing 400065, PR China.

出版信息

Carbohydr Res. 2005 Oct 31;340(15):2345-51. doi: 10.1016/j.carres.2005.08.010.

DOI:10.1016/j.carres.2005.08.010

PMID:16150428

Abstract

A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.

摘要

通过关键中间体月桂基 2,3,4,6-四-O-苯甲酰基-β-D-吡喃半乳糖基-(1→4)-2,3,6-三-O-苯甲酰基-β-D-吡喃葡萄糖基-(1→3)-2,4-二-O-苯甲酰基-β-D-吡喃葡萄糖苷（10）和异丙基 2,4,6-三-O-乙酰基-3-O-烯丙基-β-D-吡喃葡萄糖基-(1→3)-[2,3,4,6-四-O-苯甲酰基-β-D-吡喃葡萄糖基-(1→6)]-2,4-二-O-乙酰基-β-D-吡喃葡萄糖基-(1→3)-2,4,6-三-O-乙酰基-1-硫代-β-D-吡喃葡萄糖苷（15），实现了月桂基七糖 17 的简洁有效合成。关键三糖糖基受体 10 通过将 2,3,4,6-四-O-苯甲酰基-β-D-吡喃半乳糖基-(1→4)-2,3,6-三-O-苯甲酰基-α-D-吡喃葡萄糖基三氯乙酰亚胺酯（3）与月桂基 6-O-乙酰基-2,4-二-O-苯甲酰基-β-D-吡喃葡萄糖苷（9）偶联，然后脱乙酰化构建而成。硫代糖苷供体 15 通过将 2,4,6-三-O-乙酰基-3-O-烯丙基-β-D-吡喃葡萄糖基-(1→3)-[2,3,4,6-四-O-苯甲酰基-β-D-吡喃葡萄糖基-(1→6)]-2,4-二-O-乙酰基-α-D-吡喃葡萄糖基三氯乙酰亚胺酯（11）与异丙基 4,6-O-亚苄基-1-硫代-β-D-吡喃葡萄糖苷（12）缩合，然后脱亚苄基化和乙酰化得到。对 S180 实体瘤抑制的生物测定表明，月桂基七糖 17 可作为一种潜在的癌症治疗药物。