Scaffold-Oriented Asymmetric Catalysis: Conformational Modulation of Transition State Multivalency during a Catalyst-Controlled Assembly of a Pharmaceutically Relevant Atropisomer.
Chemistry
; 30(30): e202401109, 2024 May 28.
Article
in En
| MEDLINE
| ID: mdl-38507249
ABSTRACT
A new class of superbasic, bifunctional peptidyl guanidine catalysts is presented, which enables the organocatalytic, atroposelective synthesis of axially chiral quinazolinediones. Computational modeling unveiled the conformational modulation of the catalyst by a novel phenyl urea N-cap, that preorganizes the structure into the active, folded state. A previously unanticipated noncovalent interaction involving a difluoroacetamide acting as a hybrid mono- or bidentate hydrogen bond donor emerged as a decisive control element inducing atroposelectivity. These discoveries spurred from a scaffold-oriented project inspired from a fascinating investigational BTK inhibitor featuring two stable chiral axes and relies on a mechanistic framework that was foreign to the extant lexicon of asymmetric catalysis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hydrogen Bonding
/
Molecular Conformation
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
United States