Build/couple/pair strategy for the synthesis of stereochemically diverse macrolactams via head-to-tail cyclization.

ACS Comb Sci
Authors
Keywords
Abstract

A build/couple/pair (B/C/P) strategy was employed to generate a library of 7936 stereochemically diverse 12-membered macrolactams. All 8 stereoisomers of a common linear amine precursor were elaborated to form the corresponding 8 stereoisomers of two regioisomeric macrocyclic scaffolds via head-to-tail cyclization. Subsequently, these 16 scaffolds were further diversified via capping of two amine functionalities on SynPhase Lanterns. Reagents used for solid-phase diversification were selected using a sparse matrix design strategy with the aim of maximizing coverage of chemical space while adhering to a preset range of physicochemical properties.

Year of Publication
2012
Journal
ACS Comb Sci
Volume
14
Issue
2
Pages
89-96
Date Published
2012 Feb 13
ISSN
2156-8944
DOI
10.1021/co200161z
PubMed ID
22252910
PubMed Central ID
PMC3289975
Links
Grant list
UL1DE019585 / DE / NIDCR NIH HHS / United States
RL1HG004671 / HG / NHGRI NIH HHS / United States
RL1CA133834 / CA / NCI NIH HHS / United States
UL1 DE019585 / DE / NIDCR NIH HHS / United States
RL1GM084437 / GM / NIGMS NIH HHS / United States
P50 GM069721-11 / GM / NIGMS NIH HHS / United States
RL1 HG004671-05 / HG / NHGRI NIH HHS / United States
P50 GM069721 / GM / NIGMS NIH HHS / United States
RL1 GM084437 / GM / NIGMS NIH HHS / United States
RL1 HG004671 / HG / NHGRI NIH HHS / United States
RL1 CA133834 / CA / NCI NIH HHS / United States