Open AccessDe Novo Synthesis of the DEF-Ring Stereotriad Core of the Veratrum Alkaloids
Author(s) -
Matthew A. Horwitz,
Jacob G. Robins,
Jeffrey S. Johnson
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c00685
Subject(s) - stereochemistry , chemistry , cyclopamine , ring (chemistry) , vicinal , alcohol , derivative (finance) , biochemistry , organic chemistry , hedgehog , financial economics , economics , gene
The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine ( 1 ), cyclopamine ( 2 ), and veratramine ( 3 ) is reported. Starting from a known β-methyltyrosine derivative ( 8 ), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization is demonstrated to be a viable approach for the synthesis of the spirocyclic DE ring junction found in jervine and cyclopamine.