Optically Active Total Synthesis of Clavicipitic Acid

Total Synthesis of (+)‐Isatisine A

“…Acetonide formation was concomitant with silyl ether removal giving 17 in 83 % overall yield. In order to set up indole oxidation, the N-tosyl group was removed under the influence of magnesium metal in methanol, [11] giving 18 in 77 % yield. In what proved to be a wonderfully efficient strategy, isatisine A acetonide (2) was produced from 18 in a simple two-step procedure with no intermediate purification.…”

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

“…Palladium-catalyzed N-allylation of 4-bromotryptophan (dl-8) with 1,1-dimethylallyl alcohol (9) These results clearly show that the amino group must be protected. Therefore, we carried out the reaction of dl-NBoc-4-bromotryptophan (dl-18) with 9 in the presence of a catalytic amount of Pd(OAc) 2 , TPPTS, and NaHCO 3 (3 equiv.)…”

“…We have already reported the synthesis [9] in three steps from 4-bromoindole of almost enantiomerically pure (95% ee), fully protected N-Boc-1-tosyl-4-bromotryptophan methyl ester (S-14a). S-14a was detosylated by treatment with Mg/MeOH, and the resulting ester 14b was hydrolyzed with 4% aq.…”

“…We have already reported [9] the four-step synthesis of optically active cis-and trans-clavicipitic acids (6) from (S)-NBoc-1-tosyl-4-bromotryptophan methyl ester (S-14a) via 4-vinyltryptophan (15a) (Scheme 4). The key step of this route was the one-pot transformation of 15a to 17 by deprotection of the Boc group and subsequent cyclization of the amine 16.…”

“…Table 2. Results of Heck reaction of 4-bromotryptophan (8) with 1,1-dimethylallyl alcohol (9) We had obtained the pure potassium salt of 10 [M ϭ K] in good yield. Treatment of 10 with 50% AcOH (50°C, 3 h) resulted in a smooth cyclization, giving 6 in 78% yield as a isomeric mixture.…”