Creation of novel chiral synthons with enzymes: application to enantioselective synthesis of antibiotics.
Retrosynthesis was carried out to generate, from a target molecule, a symmetric diester in the prochiral or meso form. The symmetric diester was subjected to asymmetric hydrolysis with pig liver esterase to create the corresponding chiral half-ester. The chiral half-ester was converted into the target molecule by organic synthesis. Thus, various types of carbapenem antibiotics, negamycin, showdomycin, 6-azapseudouridine, cordycepin, aristeromycin, neplanocin A, and precursors of fortimicin were efficiently synthesized with the desired absolute configuration. The methods for asymmetric synthesis starting from substrates with sigma-symmetry have been extensively developed.
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D000599:Amino Acids, Diamino; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001665:Binding Sites; D003510:Cyclohexanes / Q000138:chemical synthesis; D003839:Deoxyadenosines / Q000138:chemical synthesis; D004798:Enzymes / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism; D066298:In Vitro Techniques; D008956:Models, Chemical; D012787:Showdomycin / Q000138:chemical synthesis; D013237:Stereoisomerism; D013552:Swine; D013845:Thienamycins / Q000138:chemical synthesis
D000599:Amino Acids, Diamino; D000900:Anti-Bacterial Agents; D003510:Cyclohexanes; D003839:Deoxyadenosines; D004798:Enzymes; D013845:Thienamycins; C030034:aristeromycin; C030883:carpetimycin A; C031096:neplanocin A; C031989:asparenomycin; C100200:negamycin; D012787:Showdomycin; D004950:Esterases; D000241:Adenosine; C015537:thienamycin