Combinatorial chemistry of natural products: Solid phase synthesis of D- and L-cycloserine derivatives

An efficient methodology for a solid phase synthesis of D- and L-cycloserin e derivatives is described. Fmoc-D-cycloserine 4 and its L-enantiomer 5 pre pared by a selective amine acylation of bis-silylated parent compounds are immobilized on Sasrin or 2-chlorotrityl linker resins using Mitsunobu-type reaction or direct tritylation, respectively. The resulting Fmoc-cycloserin e resins 7, 10, and 11 are deprotected with piperidine in DMF or DCM to gen erate immobilized cycloserine reagents with a primary amino group exposed f or various synthetic transformations. An example of the parallel D-cycloser ine library synthesis on a reaction plate is described. (C) 1998 Elsevier S cience Ltd. All rights reserved.