60 Carbapenem系抗生物質の一般的合成

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Naturally occurring β-lactam antibiotics which belong to the group carbapenem are still increasing in number and have attracted a great deal of synthetic study because of their unique structure and interesting biological activity. They can be classified into three groups (trans, cis, and ene-types) according to the structural mode of the side chain of the β-lactam ring. The requirements for the efficient and stereocontrolled syntheses of them having the desired absolute configuration at C-4 are indeed demanding in the exploitation of such highly potential β-lactam antibiotics. We wish to report here an efficient methodology applicable versatilely for the preparation of all kinds of carbapenems starting from (S)-3-[(benzyloxycarbonyl)amino]-4-(methoxycarbonyl)butyric acid (2) prepared by an enzyme-mediated hydrolysis of the prochiral ester (1). (1) trans-Carbapenem antibiotics were able to synthesize in a most straightforwatd manner by introducing the side chains to 7. Thus, 9 and 14, the known intermediates for PS-5 and thienamycin, respectively, were successfully prepared. (2) A synthesis of ene-carbapenem antibiotic, asparenomycin C, was also accomplished starting from 7. The characteristic feature of this approach includes the combination of chelation-controlled aldol reaction and Peterson-olefination, effecting the requisite E-tetrasubstituted olefin in the β-lactam ring. (3) Finally, cis-carbapenem antibiotic, carpetimycin A, was successfully synthesized in a stereocontrolled manner, which employs an efficient conversion of a trans-substituted δ -lactone 26 to a cis-substituted β-lactam 29, starting from chiral half ester 2.
1983-09-15

60 Carbapenem系抗生物質の一般的合成

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