α-葡萄糖苷酶抑制剂阿卡波糖的生物合成研究：同位素标记的2-表-5-表-戊糖酮类似物的化学合成

Biosynthetic studies on the alpha-glucosidase inhibitor acarbose: the chemical synthesis of isotopically labeled 2-epi-5-epi-valiolone analogs.

作者信息

Arakawa Kenji, Bowers Simeon G, Michels Benjamin, Trin Vu, Mahmud Taifo

机构信息

Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.

出版信息

Carbohydr Res. 2003 Sep 26;338(20):2075-82. doi: 10.1016/s0008-6215(03)00315-x.

DOI:10.1016/s0008-6215(03)00315-x

PMID:14505874

Abstract

2-epi-5-epi-valiolone is a cyclization product of the C(7) sugar phosphate, sedoheptulose 7-phosphate, involved in the biosynthesis of the aminocyclitol moieties of acarbose, validamycin, and pyralomicin. As part of our investigation into the pathway from 2-epi-5-epi-valiolone to the valienamine moiety of acarbose, we prepared 1-epi-5-epi-(6-(2)H(2))valiolol [(6-(2)H(2))-6], 5-epi-(6-(2)H(2))valiolol [(6-(2)H(2))-17], 1-epi-2-epi-5-epi-(6-(2)H(2))valiolol [(6-(2)H(2))-12] and 2-epi-5-epi-(6-(2)H(2))valiolamine [(6-(2)H(2))-11]. Compounds (6-(2)H(2))-6 and (6-(2)H(2))-17 were synthesized from 2,3,4,6-tetra-O-benzyl-D-glucopyranose in 10 and seven steps, respectively, whereas (6-(2)H(2))-12 and (6-(2)H(2))-11 were synthesized from 2,3,4,6-tetra-O-benzyl-D-mannopyranose in eight and 10 steps, respectively.

摘要

2-表-5-表-变紫罗酮是1,7-二磷酸景天庚酮糖（C(7)磷酸糖）的环化产物，参与阿卡波糖、井冈霉素和吡咯米星氨基环醇部分的生物合成。作为我们对从2-表-5-表-变紫罗酮到阿卡波糖缬氨霉素部分的途径研究的一部分，我们制备了1-表-5-表-(6-(2)H(2))变紫罗醇[(6-(2)H(2))-6]、5-表-(6-(2)H(2))变紫罗醇[(6-(2)H(2))-17]、1-表-2-表-5-表-(6-(2)H(2))变紫罗醇[(6-(2)H(2))-12]和2-表-5-表-(6-(2)H(2))缬氨胺[(6-(2)H(2))-11]。化合物(6-(2)H(2))-6和(6-(2)H(2))-17分别由2,3,4,6-四-O-苄基-D-吡喃葡萄糖经10步和7步合成，而(6-(2)H(2))-12和(6-(2)H(2))-11分别由2,3,4,6-四-O-苄基-D-甘露吡喃糖经8步和10步合成。