Antibiotic Synthesis Based on Symmetrization-asymmetrization Concept

Abstract

We have shown that the enantioselective total synthesis of some useful antibiotics can be efficiently achieved by reasonable combination of enzymatic and non-enzymatic procedures. Our synthetic strategy for such optically active natural products is designed by the following principle.
(1) Symmetrization : retrosynthesis is performed to generate, from the target molecule, a simplified symmetric diester in the prochiral or meso form as shown in Figure 1.
(2) Asymmetrization : the symmetric diester is subjected to asymmetric hydrolysis with pig liver esterase (PLE) to generate the corresponding chiral half-ester (Enzymatic conversion of σ-symmetry substrate to C₁-symmetry intermediate)
(3) Non-enzymatic procedures : the chiral half-ester is converted to the target molecule and related molecules by means of usual organic synthesis, including some new method developed by us. Thus, various types of carbapenem antibiotics, negamycin, showdomycin, 6-azapseudouridine, cordycepin, aristeromycin, neplanocin A, and aminocyclitol-derivatives of fortimicin were efficiently synthesized with the desired absolute configurations.