Effect of solvent on racemization in carbodiimide mediated solid phase fragment condensations

Article abstract of DOI:10.1016/S0040-4039(00)77583-6

The Izumiya tripeptide was used to assess racemization in solid-phase fragment condensations. Boc-Gly-Ala-OH¹ was coupled to Leu-PAM resin with DIC in a variety of solvents, both with and without HOBt. After cleavage from the resin, the extent of racemization was determined using C18 RP-HPLC to separate the epimers. Solvents used were DMF, NMP, TFE, and each of these as mixtures with DCM. Also tested was a mixture of NMP and DMSO (85:15). Couplings in FMD/DCM (1:1) and NMP/DCM (1:1) in the presence of HOBt were in excess of 98% and racemization was undetectable (<0.1%).