Biology-oriented synthesis of stereochemically diverse natural-product-derived compound collections by iterative allylations on a solid support.
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 alpha,beta-unsaturated delta-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.
Umarye
Jayant D
JD
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Lessmann
Torben
T
García
Ana B
AB
Mamane
Victor
V
Sommer
Stefan
S
Waldmann
Herbert
H
D000498:Allyl Compounds / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis*; D008956:Models, Chemical; D018716:Molecular Mimicry; D011108:Polymers / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000498:Allyl Compounds; D001688:Biological Products; D007783:Lactones; D011108:Polymers; C024617:polyol