66667-02-5Relevant articles and documents
Synthesis of endothiopeptides by using the 'Azirine/Oxazolone method
Baertsch,Bischof,Heimgartner
experimental part, p. 195 - 206 (2009/10/17)
The reaction of terf-butyl- or THP-protected mandelic thioacid (7a and 7b) with N,N,2,2-tetramethyl-2H-azirin-3-amine (2a) gave the dipeptide analogues tBu- and THP-Mns-Aibψ[CS]NMe2 (8a and 8b, resp.) with a C-terminal thioamide group. Treatment of 8a with HCI gas in toluene led to 2-(l-tert-butoxybenzyl)- 4,4-dimethyl-1,3- thiazole-5(4H)-one (9); which reacted with dimethylamine via ring opening to give tBu-Mnsψ[CSNH]Aib-NMe2 (11a), an isomer of 8a with the thioamide group within the chain, i.e., the product of a sulfur migration. In the case of 8b, selective deprotection of the THP-hydroxy group was achieved by treatment with pyridinium p-toluenesulfonate (PPTS) in ethanol. Cyclization of the resulting Mns-Aibψ[CS]NMe2 (13) yielded the 2-thioxomorpholin-5-one 10. In a similar manner, Boc-Val-SH (14) reacted with azirine 2b to give Boc-Val-Aibψ[CS]N(Me)Ph (15a), which was transformed to Fmoc-Val-Aibψ[CS]N(Me)Ph (15b) and further to Fmoc-Valψ[CSNH]Aib-N(Me)Ph (16) by treatment with ZnCl2 in acetic acid. Coupling of two of these molecules via the l,3-thiazol-5(4H)-one 17 yielded the endodithiopeptide Fmoc-Vaψ[CSNH]Aib- Valψ[CSNH]Aib-N(Me)Ph (19).
