Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.
Beilstein J Org Chem. 2011;7:1609-19. doi: 10.3762/bjoc.7.189. Epub 2011 Dec 1.
Phenyl 3,4,6-tri-O-benzyl-2-O-(3-carboxypropionyl)-1-thio-β-D-galactopyranoside (1) was condensed via its pentafluorophenyl ester 2 with 5-aminopentyl (4a), 4-aminobutyl (4b), 3-aminopropyl (4c) and 2-aminoethyl 4,6-O-benzylidene-β-D-glucopyranoside (4d), prepared from the corresponding N-Cbz protected glucosides 3a-d, to give the corresponding 2-[3-(alkylcarbamoyl)propionyl] tethered saccharides 5a-d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the tethered β(1→3) linked disaccharides 6a-c, the α(1→3) linked disaccharides 7a-d and the α(1→2) linked disaccharide 8d in ratios depending upon the ring size formed during glycosylation. No β(1→2) linked disaccharides were formed. Molecular modeling of saccharides 6-8 revealed that a strong aromatic stacking interaction between the aromatic parts of the benzyl and benzylidene protecting groups in the galactosyl and glucosyl moieties was mainly responsible for the observed regioselectivity and anomeric selectivity of the ring-closing glycosylation step.
苯基 3,4,6-三-O-苄基-2-O-(3-羧基丙酰基)-1-硫代-β-D-半乳糖吡喃糖苷（1）通过其五氟苯基酯 2 与 5-氨基戊基（4a）、4-氨基丁基（4b）、3-氨基丙基（4c）和 2-氨基乙基 4,6-O-苄叉基-β-D-吡喃葡萄糖苷（4d）缩合，后者由相应的 N-Cbz 保护的葡萄糖苷 3a-d 制备，得到相应的 2-[3-（烷氨基甲酰基）丙酰基]连接的糖 5a-d。糖的分子内环 Closing 糖苷化反应，使用 NIS 和 TMSOTf，得到了连接的β（1→3）二糖 6a-c、α（1→3）连接的二糖 7a-d 和α（1→2）连接的二糖 8d，这取决于在糖苷化过程中形成的环大小的比例。没有形成β（1→2）连接的二糖。糖 6-8 的分子建模表明，在半乳糖基和葡萄糖基部分中苄基和苄叉保护基的芳基部分之间存在强烈的芳环堆积相互作用，这主要负责观察到的环 Closing 糖苷化步骤的区域选择性和非对映选择性。
