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.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, PA 19104, USA. smithab@sas.upenn.edu
Kanoh
Naoki
N
Ishiyama
Haruaki
H
Minakawa
Noriaki
N
Rainier
Jon D
JD
Hartz
Richard A
RA
Cho
Young Shin
YS
Cui
Haifeng
H
Moser
William H
WH
D026121:Indole Alkaloids / Q000737:chemistry*; D009183:Mycotoxins / Q000138:chemical synthesis*; D010407:Penicillium / Q000737:chemistry
D026121:Indole Alkaloids; D009183:Mycotoxins; C003626:tremortin