Stereoselective syntheses of galanthamine and its stereoisomers by complementary Luche and L-selectride reductions

作者：Trinadhachari G****a Naga; Kamat Anand Gopalkrishna; Babu Korupolu Raghu; Sanasi Paul Douglas; Prabahar Koilpillai Joseph^*

来源：Tetrahedron: Asymmetry , 2014, 25(2): 117-124.

DOI：10.1016/j.tetasy.2013.11.016

A diastereodivergent approach for the stereoselective syntheses of all four stereoisomers of galanthamine, (-)-galanthamine 1, (+)-galanthamine 2, (-)-epigalanthamine 3, and (+)-epigalanthamine 4, from (+/-)-narwedine 5 is reported. Thus (+/-)-narwedine 5 was resolved by dynamic kinetic resolution to obtain enantiomerically pure (-)-narwedine 6 and (+)-narwedine 7. Each enantiomerically pure isomer of narwedine was subjected to Luche and L-selectride reactions to obtain all four isomers of galanthamine. In these reactions, the (-)-galanthamine 1 and (+)-galanthamine 2 isomers were obtained with an enantiomeric purity of >99.5%, whereas (-)-epigalanthamine 3 and (+)-epigalanthamine 4 are obtained with a chiral purity of >97%. The axial hydride attack by the Luche reduction and the equatorial hydride attack by the L-selectride reduction on the cyclic enone system are explored in the stereoselective synthesis of the galanthamine isomers and thus it was demonstrated that the stereoselective synthesis involving the Luche and L-selectride reductions are complementary in yielding enantiomeric stereogenic centers from a prochiral carbonyl group on the cyclic enone system.

• 出版日期2014-1-31