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Tremorgenic Indole Alkaloids. The Total Synthesis of (−)-Penitrem D

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posted on 11.06.2003, 00:00 by Amos B. Smith, Naoki Kanoh, Haruaki Ishiyama, Noriaki Minakawa, Jon D. Rainier, Richard A. Hartz, Young Shin Cho, Haifeng Cui, William H. Moser
A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (−)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)3-promoted reaction cascade. The longest linear sequence leading to (−)-penitrem D (4) was 43 steps.