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

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-H-2(2))valiolol [(6-H-2(2))-6], 5-epi-(6-H-2(2))valiolol [(6-H-2(2))-17], 1-epi-2-epi-5-epi-(6-H-2(2))valiolol [(6-H-2(2))-12] and 2-epi-5-epi-(6-H-2(2))valiolamine [(6-H-2(2))-11]. Compounds (6-H-2(2))-6 and (6-H-2(2))-17 were synthesized from 2,3,4,6-tetra-O-benzyl-D-glucopyranose in 10 and seven steps, respectively, whereas (6-H-2(2))-12 and (6-H-2(2))-11 were synthesized from 2,3,4,6-tetra-O-benzyl-D-mannopyranose in eight and 10 steps, respectively. (C) 2003 Elsevier Ltd. All rights reserved.