The chemistry of some 2-aminothiazol-4-ylacetic acid derivatives and the synthesis of derived penicillins

Abstract

The N-protected 2-aminothiazol-4-ylacetic acid derivatives (6), (11), (14), (16), (18), (26), (27), (30), (33), and (34) have been prepared. They are readily available by reaction of the corresponding 2-amino ethyl esters such as (1) with the appropriate acylating agents, generally giving a bis-carbamate of type (5), followed by saponification. The process is general for α-methylene, α-oximino, and α-amino substituents in the side-chain affording in the last case a route to differentially protected α-amino-α-(2-aminothiazol-4-yl)acetic acids such as (30). The optimum conditions for the acylations are described; the course of the saponification of the bis-carbamate esters is discussed and physical evidence for the structures of the derivatives is presented. The use of the protected acids (11) and (34) in the synthesis of the piperacillin analogue (38) is described.