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

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.