Green diastereospecific synthesis of various medicine analogues containing dipeptides and release of the medicines by Baker's yeast. (19th November 2022)

• Record Type: Journal Article
• Authors: Jung, Sunghee; Satoh, Shin; Daitoku, Hideyuki; Noguchi, Takuya; Kawashima, Yuya; Imai, Nobuyuki
• Is Part Of: Tetrahedron. Volume 127(2022)
• Publication Date: 2022-11-19
• Subjects: Green synthesis -- Diastereospecific -- Medicine analogue -- Dipeptide -- Biocatalyst -- Baker's yeast; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2022.133102
• Languages: English
• ISSNs: 0040-4020

Abstract

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-NHC6 H4 -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 PhCH2 CH2 CO2 CO2 Et from 3-phenylpropanoic acid, ClCO2 Et, and Et3 N in MeCN to afford PhCH2 CH2 CONHC6 H4 -4-OH and PhCH2 CH2 CO-l -Phe-NHC6 H4 -4-OH in 46% and 42% yields, respectively. Interestingly, biocatalytic hydrolysis of l -Phe-d -Phe-NHC6 H4 -4-OH by Baker's yeast gave PhCH2 CH2 CO-d -Phe-NHC6 H4 -4-OH in 20% yield and PhCH2 CH2 CO-l -Phe-d -Phe-NHC6 H4 -4-OH 60% recovery yield. Graphical abstract: Image 1