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

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