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

• Published in: European journal of organic chemistry Vol. 2004; no. 6; pp. 1244 - 1253
• Main Authors: Yokoyama, Yuusaku, Hikawa, Hidemasa, Mitsuhashi, Masaharu, Uyama, Aki, Hiroki, Yasuhiro, Murakami, Yasuoki
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.03.2004; WILEY‐VCH Verlag; Wiley
• Subjects: Chemistry; Chemistry, Organic; Clavicipitic acids; Heck reaction; Physical Sciences; Protecting groups; Science & Technology; Total synthesis; Tryptophan; protecting groups; PRACTICAL SYNTHESIS; CARBONYLATION; FORMAL SYNTHESIS; BIOSYNTHESIS; Heck reaction; CHEMISTRY; clavicipitic acids; total synthesis; tryptophan; INDOLES; CONJUGATE ADDITION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200300603

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 C4‐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)