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Total Synthesis without Protection: Three‐Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic Route
Author(s) -
Yokoyama Yuusaku,
Hikawa Hidemasa,
Mitsuhashi Masaharu,
Uyama Aki,
Hiroki Yasuhiro,
Murakami Yasuoki
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300603
Subject(s) - chemistry , heck reaction , optically active , palladium , aqueous medium , combinatorial chemistry , biomimetic synthesis , total synthesis , stereochemistry , organic chemistry , aqueous solution , catalysis
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)