124286-64-2Relevant academic research and scientific papers
Total Synthesis of (+/-)-Vallesamidine
Heathcock, Clayton H.,Norman, Mark H.,Dickman, Dan A.
, p. 798 - 811 (1990)
This article reports full details of a project aimed at providing synthetic access to the 2,2,3-trialkylindoline alkaloids such as vallesamidine (4).The basic strategy was to preassemble the tricyclic portion containing the nonindolic nitrogen and to form the indoline ring at a late stage in the synthesis.An approach summarized in the retrosynthetic analysis summarized in Scheme III failed because enones 48 and 50 do not undergo 1,4-addition of nitrogen nucleophiles.However, the retrosynthesis summarized in Scheme X did lead to a sucessful synthesis of (+/-)-4.Thesynthesis requires seven steps from 2-ethylcylopentanone 54 -> 56 -> 66 -> 68 -> 71 -> 74 -> (+/-)-4> and delivers the alkaloid in 19percent overall yield.Pivotal steps in the synthesis are the lactam annelation process in which 56 reacts with o-nitrocinnamic acid to yield 66 and the NBS-mediated cyclization of amino lactam 68 to the pentacyclic bromo lactam 70.Four of seven steps involve the formation of skeletal (C-C or C-N) bonds and only three are functional-group transformations.
