A combinatorial synthesis of tyrphostins via the "directed sorting" method.

Abstract:

: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.

journal_name

Biotechnol Bioeng

authors

Shi S,Xiao XY,Czarnik AW

doi

10.1002/(sici)1097-0290(199824)61:1<7::aid-bit4>3.

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

7-12

issue

1

eissn

0006-3592

issn

1097-0290

pii

10.1002/(SICI)1097-0290(199824)61:1<7::AID-BIT4>3.

journal_volume

61

pub_type

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