A combinatorial synthesis of tyrphostins via the "directed sorting" method.
Using solid-phase organic synthesis, we have prepared a 432-member (18 x 8 x 3) sample library based on the AG 490 "tyrphostin" template. By utilizing 432 reactors each equipped with a unique radiofrequency memory ID tag, the 432 products could be obtained as discrete entities (i.e., not as mixtures) via 18 + 8 + 3, or 29 reactions. Reading each ID tag after each reaction step permitted the "directed sorting" of reactors into appropriate reaction vessels containing multiple reactors. After synthesis, all products were cleaved from the solid-phase support and lyophilized to afford powders. Characterization of 5% of the library members by NMR and mass spectrometry provided verification of structure. In addition, TLC analysis of every library member provided evidence that most (or all) are composed of a single major organic compound. Some 88% of these samples were obtained in amounts of between 5 and 19 mg. Using this reaction sequence and the "directed sorting" approach, the synthesis of much larger AG 490-based libraries can be envisioned.
Shi
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Department of Chemistry, IRORI, La Jolla, California 92037-1031, USA.
Xiao
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Czarnik
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D000107:Acetylation; D000447:Aldehydes / Q000737:chemistry; D000586:Amination; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004951:Esterification; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D019151:Peptide Library; D020032:Tyrphostins / Q000138:chemical synthesis*
D000447:Aldehydes; D019151:Peptide Library; D020032:Tyrphostins; C116609:3-hydroxybutanal