Total Synthesis without Protection: Three‐Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic Route

Abstract

Abstract A three‐step synthesis of a mixture of optically active cis ‐ and trans ‐clavicipitic acids 6 , which are ergot alkaloids, was achieved, starting from 4‐bromoindole ( 7 ) and dl ‐serine ( dl ‐ 2 ). This short synthesis was made possible by omitting the protection and deprotection steps from the synthetic route. The key step was the spontaneous cyclization of 4‐vinyltryptophan ( 10 ) formed from the Heck reaction of 4‐bromotryptophan ( 8 ) with 2‐methyl‐3‐buten‐2‐ol ( 9 ) in aqueous media. During this investigation, we also found that the palladium‐catalyzed reaction of 8 with 9 showed an interesting pH dependence; under strongly basic conditions, the Heck reaction occurred to give a C 4 ‐vinylated product 10 , whereas an N ‐allylated product 19b was formed under neutral or weakly basic conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)