Clavicipitic acid optically active, synthesis

An asymmetric version of the total synthesis of clavicipitic acid was reported by Yokoyama et al. [82-84]. As illustrated in Scheme 29 asymmetric hydrogenation of the known 4-bromodehydrotryptophan 163 was best achieved (94% ee) using the optically active Monsanto bidentate phosphine, DIPAMP. The Heck vinylation in the presence of Ag,CO, gave the C(4)-vinylated product 168 without racemization. Treatment of 168 with HCl-EtOAc effected the cyclization to give the tricyclic azepinoindole 170 (62%), al.- ig with diene 169 (29%). Cleavage of the sulfonamide (Mg/MeOH) afforded 171 which underwent saponification (KOH) to give optically active clavicipitic acid (167). 

For the production of natural products on an industrial scale, fermentation processes are often preferable in comparison to chemical processes. In biosynthesis processes, natural products may be generated efficiently and cleanly via enzymatic catalysis 185). Thus, the development of synthesis approaches similar to their biosynthesis is one of the main objectives of the synthesis community. To pursue this goal, Yokoyama and co-workers developed a bio-similar three-step synthesis of optically active clavicipitic acid (175) 186), which was isolated from natural sources as an isomeric mixture (Scheme 4.10) 187). 

Yokoyama Y, Hikawa H, Mitsuhashi M, Uyama A, Hiroki Y, Murakami Y (2004) Total Synthesis Without Protection Three-Step Synthesis of Optically Active Clavicipitic Acids by a Biomimetic Route. Eur J Org Chem 1244... 

Yokoyama, Y, Matsumoto, T. and Murakami, Y. (1995) Optically active total synthesis of clavicipitic acid. J. Org. Chem., 60, 1486-7. 

Yokoyama, Y, Hikawa, H., Mitsuhashi, M. et al. (1999) Syntheses without protection a three-step synthesis of optically active clavicipitic acid by utilizing biomimetic synthesis of 4-bromolryptophan. Tetrahedron Lett., 40,7803-6. 

Yokoyama, Y, Hikawa, H. and Murakami, Y. (1997) Organic S5mthesis without protecting group total synthesis of optically active clavicipitic acid in aqueous media. Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 39, 325-30 Chem. Abstr., 131, 73829 (1999). 

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