抄録
Serotobenine (1) was isolated from the seed of safflower by Sato and co-worker in 1985 and the structurally-related compound decursivine (3) was isolated by Fong et al. in 2002 Both of these compounds 1 and 3 are characterized by the fused polycyclic ring systems including indole, dihydrobenzofuran and 8-membered lactam rings. Although biosynthesis of both compounds would be similar, 1 existed as a racemic form and 3 was composed of an optically active form. The difference of stereochemistry also prompted us to investigate the synthetic study of these compounds. Herein, we report the total synthesis of optically active serotobenine (1). Recently we found that an intramolecular C-H insertion reaction by the combination of Davies Rh catalyse and the chiral auxiliary provided an optically active trans-2,3-dihydro-3-benzofuran derivatives efficiently. We envisioned that this method would be applicable for the synthesis of the optically active dihydrobenzofuran ring of 1. The indole derivative 9, readily synthesized by Leimgruber-Batcho's protocol was converted to 4-allylindole derivative 10 by regioselective Claisen rearrangement (Scheme 4). As shown in Scheme 5, conversion to the diazoester 15 from 10 was achieved by diazotransfer reaction. Upon treatment of 15 with achiral rhodium catalyst Rh_2(OAc)_4, the C-H insertion reaction was proceeded smoothly to afforded dihydrobenzofuran 16 in high diastereoselectivity. After the transformation to the activated ester 18, construction of 8-membered lactam ring was accomplished by after reduction of azide group. Finally, deprotection of Ts group and Bn group was carried out in stepwise manner and total synthesis of (-)-serotobenine (1) has been accomplished. We are currently investigating the stereochemical behavior of 1, according to our racemization hypothesis, as shown in Scheme I.
