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Biology‐Oriented Synthesis of Stereochemically Diverse Natural‐Product‐Derived Compound Collections by Iterative Allylations on a Solid Support
Author(s) -
Umarye Jayant D.,
Leßmann Torben,
García Ana B.,
Mamane Victor,
Sommer Stefan,
Waldmann Herbert
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601698
Subject(s) - stereocenter , diastereomer , chemistry , natural product , acryloyl chloride , enantioselective synthesis , stereochemistry , metathesis , organic chemistry , enantiomer , stereoselectivity , combinatorial chemistry , polymerization , polymer , catalysis , monomer , acrylate
A strategy aiming at the introduction of stereocenters into polymer‐bound natural‐product‐derived and ‐inspired compound collections is presented. Treatment of immobilized aldehydes with Brown's pinene‐derived allylboranes results in the stereoselective formation of homoallylic alcohols with up to 89 % ee ( ee =enantiomeric excess). Subsequent iterative ozonolysis–allylation sequences with up to three allylations on a solid support give access to 1,3‐polyols with different relative configurations. Esterification with acryloyl chloride and final ring‐closing metathesis yields α,β‐unsaturated δ‐lactones with multiply oxygenated side chains, a substructure found in a group of natural products with a broad range of biological activity. The flexibility of the approach is exemplified by the parallel synthesis of all eight diastereomers of cryptocarya diacetate on a solid support. The individual isomers are obtained in overall yields of 40–60 % over 10 steps and with 63–85 % diastereoselectivity for the major isomer.