Gary W. Luehr

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

Abstract An efficient methodology for a solid phase synthesis of D- and L-cycloserine derivatives is described. Fmoc-D-cycloserine 4 and its L-enantiomer 5 prepared 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-cycloserine resins 7, 10, and 11 are deprotected with piperidine in DMF or DCM to generate immobilized cycloserine reagents with a primary amino group exposed for various synthetic transformations. An example of the parallel D-cycloserine library synthesis on a reaction plate is described.