A modular synthetic approach toward exhaustively stereodiversified ligand libraries.
[structure] This report describes a modular approach to the synthesis of stereodiversified natural product-like libraries. Monomers 2 and 3 were coupled in parallel by silyl-tethered olefin metathesis to generate all 16 stereoisomers of cis-enediols 1. All 16 stereoisomers were incorporated into chimerae having flanking peptidic segments. These chimerae exhibited a broad range of hydrophobicities, raising the possibility that stereochemical variation might be used to tune the pharmacologic properties of small molecules.
Gierasch
T M
TM
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Chytil
M
M
Didiuk
M T
MT
Park
J Y
JY
Urban
J J
JJ
Nolan
S P
SP
Verdine
G L
GL
D000475:Alkenes / Q000138:chemical synthesis; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D008024:Ligands; D010455:Peptides / Q000138:chemical synthesis; D012833:Siloxanes / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000475:Alkenes; D008024:Ligands; D010455:Peptides; D012833:Siloxanes