Simultaneous multiple synthesis by the Multipin~TM method: Techniques for multiple handling, high throughput characterization and reaction optimization on solid phase

摘要

The Multipin~TM method of multiple solid phase synthesis allows access to large numbers of individual compounds (100s, i.e. libraries [1]) via parallel synthesis, at scales ranging from 1 to 40 mu mol/pin. synthesis is performed on polymer grafted plastic pins, which are organized in an 8 x 12 modular format. The method was first developed for the rapid elucidation of linear antibody epitopes [2], via the screening of sub-micromolar quantities of pin-bound peptide segments. With the development of new graft polymers for pins, such as poly(hydroxyethyl methacrylate) [3], acrylamide copolymers [4], and polystyrene [4], the development of hihg loading pin designs [5], and the introduction of a wide range of linker systems, the Multipin~TM mehtod can now be applied to a far wider range of synthetic problems. Since Ellman's landmark paper describing the synthesis of benzodiazepines on resin [6], there has been a dramatic growth in the field of multiple solid phase organic synthesis [1,7,8] and several examples of non-peptide synthesis on pins have been published [9-12]. Unlike soild phase peptide or oligonucleoside synthesis, solid phase organic synthesis requires that a very broad range of reaction types must proceed in high yield. Although an 80