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Symmetric building blocks and combinatorial functional group transformation as versatile strategies in combinatorial chemistry
Author(s) -
Früchtel Jörg Steffen,
Pflugseder Karin,
Gstach Hubert
Publication year - 2000
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/1097-0290(200021)71:2<94::aid-bit3>3.0.co;2-y
Subject(s) - functional group , reagent , amide , combinatorial chemistry , chemistry , ketone , bifunctional , functional diversity , group (periodic table) , aryl , alkyl , organic chemistry , polymer , catalysis , biology , ecology
A combination of symmetric building blocks and combinatorial functional group transformation for synthesis of pyrimidines was investigated. The purpose of the study was to maximize the return on invested synthetic efforts of reaction development for libraries. A representative set of symmetric diacids was coupled onto deprotected TentaGel Rink Amide resin. The amino function served as a model of a chemical process providing a functional group for additional synthetic steps, while the symmetric building blocks served as a model to connect synthesis protocols and to switch to a different synthesis paradigm consecutively. The reaction sequence was continued in a noncombinatorial step by coupling a bifunctional reagent (3‐aminoacetophenone) to the remaining carboxy function of the symmetric diacid. The ketone served as a model of a reagent prepared for combinatorial functional group transformation. The arylmethylketone was reacted with a set of aryl‐ and heteroarylaldehydes to give α,β‐unsaturated ketones. Subsequently, guanidine, alkyl‐, and arylcarboxamidines were introduced in combinatorial synthesis of substituted pyrimidines by reaction with the α, β‐unsaturated ketone functionality. The combination of symmetric building blocks and combinatorial functional group transformation created a versatile reaction sequence ideally suited for production of libraries from libraries with added diversity. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:94–103, 2000/2001.