A modular synthetic approach toward exhaustively stereodiversified ligand libraries

T M  Gierasch; M  Chytil; M T  Didiuk; J Y  Park; J J  Urban; Steven Patrick Nolan; G L  Verdine

A modular synthetic approach toward exhaustively stereodiversified ligand libraries

T M Gierasch, M Chytil, M T Didiuk, J Y Park, J J Urban, Steven Patrick Nolan, G L Verdine

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	3999-4002
Number of pages	4
Journal	Organic Letters
Volume	2
Issue number	25
Publication status	Published - 14 Dec 2000

Keywords

RING-CLOSING METATHESIS
PEPTIDE COMBINATORIAL LIBRARIES
OLEFIN METATHESIS
ORGANIC-SYNTHESIS
DRUG DISCOVERY
POLYKETIDE LIBRARIES
RUCL2(=CHR')(PR(3))(2)
PEPTIDOMIMETICS
TECHNOLOGIES
DIVERSITY

Cite this

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title = "A modular synthetic approach toward exhaustively stereodiversified ligand libraries",

abstract = "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.",

keywords = "RING-CLOSING METATHESIS, PEPTIDE COMBINATORIAL LIBRARIES, OLEFIN METATHESIS, ORGANIC-SYNTHESIS, DRUG DISCOVERY, POLYKETIDE LIBRARIES, RUCL2(=CHR')(PR(3))(2), PEPTIDOMIMETICS, TECHNOLOGIES, DIVERSITY",

author = "Gierasch, {T M} and M Chytil and Didiuk, {M T} and Park, {J Y} and Urban, {J J} and Nolan, {Steven Patrick} and Verdine, {G L}",

year = "2000",

month = dec,

day = "14",

language = "English",

volume = "2",

pages = "3999--4002",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society (ACS)",

number = "25",

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TY - JOUR

T1 - A modular synthetic approach toward exhaustively stereodiversified ligand libraries

AU - Gierasch, T M

AU - Chytil, M

AU - Didiuk, M T

AU - Park, J Y

AU - Urban, J J

AU - Nolan, Steven Patrick

AU - Verdine, G L

PY - 2000/12/14

Y1 - 2000/12/14

N2 - 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.

AB - 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.

KW - RING-CLOSING METATHESIS

KW - PEPTIDE COMBINATORIAL LIBRARIES

KW - OLEFIN METATHESIS

KW - ORGANIC-SYNTHESIS

KW - DRUG DISCOVERY

KW - POLYKETIDE LIBRARIES

KW - RUCL2(=CHR')(PR(3))(2)

KW - PEPTIDOMIMETICS

KW - TECHNOLOGIES

KW - DIVERSITY

M3 - Article

SN - 1523-7060

VL - 2

SP - 3999

EP - 4002

JO - Organic Letters

JF - Organic Letters

IS - 25

ER -

A modular synthetic approach toward exhaustively stereodiversified ligand libraries

Abstract

Keywords

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