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Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion
Author(s) -
Gholami Hadi,
Kulshrestha Aman,
Favor Olivia K.,
Staples Richard J.,
Borhan Babak
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900340
Subject(s) - hydroamination , steric effects , surface modification , chemistry , combinatorial chemistry , total synthesis , proteasome inhibitor , stereochemistry , sequence (biology) , proteasome , biochemistry , intramolecular force
The synthesis of (−)‐salinosporamide A, a proteasome inhibitor, is described. The synthesis highlights the assembly of a densely decorated pyrrolidinone core via an aza‐Payne/hydroamination sequence. Central to the success of the synthesis is a late‐stage C−H insertion reaction to functionalize a sterically encumbered secondary carbon. The latter functionalization leads to an enabling transformation where most of the prototypical strategies failed.