百部叶碱生物碱的半合成及其生物活性

Semisynthesis and biological activity of stemofoline alkaloids.

作者信息

Baird Morwenna C, Pyne Stephen G, Ung Alison T, Lie Wilford, Sastraruji Thanapat, Jatisatienr Araya, Jatisatienr Chaiwat, Dheeranupattana Srisulak, Lowlam Jaturong, Boonchalermkit Sukanya

机构信息

School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.

出版信息

J Nat Prod. 2009 Apr;72(4):679-84. doi: 10.1021/np800806b.

DOI:10.1021/np800806b

PMID:19222234

Abstract

The semisynthesis of the Stemona alkaloids (3'R)-stemofolenol (1), (3'S)-stemofolenol (2), methylstemofoline (3), and (3'S)-hydroxystemofoline (5) and the unnatural analogues (11E)-methylstemofoline (15) and 3'R-hydroxystemofoline (11) has been achieved starting from (11Z)-1',2'-didehydrostemofoline (4). This synthesis allowed, for the first time, access to diastereomerically enriched samples of 1 and 2 and the assignment of their absolute configurations at C-3'. These compounds were obtained in sufficient quantities to allow for their biological testing. In a quantitative assay as AChE inhibitors, (11Z)-1',2'-didehydrostemofoline (4) and (3'S)-hydroxystemofoline (5) were found to be the most active.

摘要

从(11Z)-1',2'-二脱氢百部碱(4)出发，实现了百部生物碱(3'R)-百部叶醇(1)、(3'S)-百部叶醇(2)、甲基百部碱(3)和(3'S)-羟基百部碱(5)以及非天然类似物(11E)-甲基百部碱(15)和3'R-羟基百部碱(11)的半合成。该合成首次实现了获得非对映体富集的1和2样品，并确定了它们在C-3'处的绝对构型。获得了足够量的这些化合物以进行生物学测试。在作为乙酰胆碱酯酶抑制剂的定量测定中，发现(11Z)-1',2'-二脱氢百部碱(4)和(3'S)-羟基百部碱(5)活性最高。