Construction of Hydroxylated Alkaloids (+/-)-Mannonolactam, (+/-)-Deoxymannojirimycin, and (+/-)-Prosopinine through Aza-Annulation

Article abstract of DOI:10.1021/jo00092a015

The aza-annulation of β-enamino carbonyl substrates with acrylate derivatives provides an efficient and convenient route for the regioselective construction of δ-lactams.This two-step ring-forming sequence involved initial generation of the benzyl enamine through either a condensation or conjugate addition reaction with BnNH2, followed by aza-annulation with acryloyl chloride or acrylic anhydride.Controlled by the rigid framework of the intermediate lactam, introduction of ring substituents was accomplished with high relative stereoselectivity.The carbonyl functionality, which was necessary to direct the regioselectivity of the aza-annulation reaction, was then transformed into a protected hydroxyl substituent through Baeyer-Villiger oxidation.The resultant δ-lactam product was used as a valuable intermediate in the synthesis of three natural products.Subsequent modification of this δ-lactam gave the naturally occurring α-mannosidase inhibitors (+/-)-mannonolactam and (+/-)-deoxymannojirimycin, while synthesis of the alkaloid (+/-)-prosopinine was accomplished through homologation of the lactam carbonyl.