Green diastereospecific synthesis of various medicine analogues containing dipeptides and release of the medicines by Baker's yeast

Abstract

We have succeeded green and economical synthesis of various dipeptides in 76–99% yields with 70–>99% de and dipeptides-containing medicine analogues in 74–99% yields with 79–97% de in aqueous THF at −15 °C via the mixed carbonic carboxylic anhydrides by the activation of the corresponding carboxylic acids. We observed that the anilide l-Phe-l-Phe-NHC6H4-4-OH, one of the deprotecting medicine analogues, was cleaved at the C-terminal of l-phenylalanine (l-Phe) by Baker's yeast under starvation conditions followed by treatment of a freshly prepared PhCH2CH2CO2CO2Et from 3-phenylpropanoic acid, ClCO2Et, and Et3N in MeCN to afford PhCH2CH2CONHC6H4-4-OH and PhCH2CH2CO-l-Phe-NHC6H4-4-OH in 46% and 42% yields, respectively. Interestingly, biocatalytic hydrolysis of l-Phe-d-Phe-NHC6H4-4-OH by Baker's yeast gave PhCH2CH2CO-d-Phe-NHC6H4-4-OH in 20% yield and PhCH2CH2CO-l-Phe-d-Phe-NHC6H4-4-OH 60% recovery yield.