11 光学活性Clavicipitic Acidの全合成(口頭発表の部)

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In the palladium-mediated vinylations of 4-bromo-1-tosylindole (8) with ethyl acrylate, the C_3-vinylated product (9) was obtained without affecting the carbon-bromine bond when stoichiometric amount of Pd(OAc)_2 was used, while the vinylation occurred at the bromine-substituted position by palladium-catalyzed vinylation (Heck reaction) to give the C_4-vinylated product (10). Those chemoselectivity are synthetically useful, because two different carbon side chains could be introduced regioselectively to aromatic bromides by applying the above reactions. The vinylations of various aromatic bromides with ethyl acrylate in the presence of stoichiometric amount of Pd(OAc)_2 were investigated. 2,4-Dimethoxybenzene (14) and p-bromoacetanilide (16) gave the vinylated product (15 and 18) without affecting the carbon-bromine bond. While the same reaction of bromothiophene (19a and 21) or bromofuran (19b) gave the di-vinyl products (20a, b and 22) as main products. Those results show that the selectivity was lost when the bromine atom was attached at too electron rich position. The synthesis of optically active clavicipitic acid (1) was accomplished in only 6 steps from 4-bromoindole (8). The 4-bromodehydrotryptophan (35) was obtained by applying the above chemoselective vinylation of 8 in the presence of stoichiometric amount of Pd(OAc)_2 in good yield. Asymmetric reduction of 35 gave the optically active 4-bromotryptophan (36). Heck reaction of 36 gave C_4-vinylated product (38) which was synthetic equivalent of an important biosynthetic intermediate, DMAT (3). Deprotection of Boc group of 38 under acidic condition caused the spontaneous cyclization to give the mixture of cis and trans-N-tosylclavicipitic acid methyl esters (40). In this route, the key step is that the two different carbon side chains were selectively introduced at C_3- and C_4-position of 8 by palladium-mediated vinylation. This short step synthesis is the first successful example that employs optically active tryptophan derivative, and this strategy provides an easy access to many optically active indole alkaloids having an tryptophan skeleton which are of synthetic and biosynthetic importance.
天然有機化合物討論会の論文
1995-09-01

11 光学活性Clavicipitic Acidの全合成(口頭発表の部)

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