60(P1-8) シス及びトラソス-6-アミノカルバペネム類の全合成(ポスター発表の部)  [in Japanese] 60(P1-8) A Total Synthesis of Cis- and Trans-6-aminocarbapenems  [in Japanese]

The enantioselective synthesis of cis- and trans-6-amino-carbapenems which are highly resistant to renal dehydropeptidase I (DHP-I) is described. 1. Synthesis of trans-6-aminocarbapenems For the search of biologically more suitable N-substituents at C-6 in carbapenems, the versatile intermediate 7 was prepared from 6-APA(Scheme 1). Although 7 was tried to convert into the carbapenems(13a-13g) with acetyl or hydrogen on the nitrogen atom at C-6, the corresponding derivatives could not be obtained because of their physico-chemical instability. The total synthesis of the desired carbapenems(14h-14k) having high stability to DHP-I, was accomplished by N-methylation. In addition, the S-side chain derivatives(22a-22i) of 14i were efficiently prepared using the [2+2] cycloaddition reaction of ketene(15')-imine(16)(Scheme 2). 2. Synthesis of cis-6-aminocarbapenems In order to find out more potent 6-aminocarbapenems, cis-aminocarbapenems were synthesized using carbene insertion to the sulfide 23 as a key step. This reaction was regio- and stereoselective, and gave cis 24a as a sole product(Scheme 4). Compound 24a-2 was decarboxylated by hydrogenolysis and treated with Raney nickel to give the N-methylated and desulfurized derivative 26