Total synthesis of lasonolide A and synthetic studies on maltophilin and aclidinomycin A

Abstract

We have established a highly enantioselective total synthesis of the natural (+)-lasonolide A 1 via Wittig reaction of aldehyde 218 with phosphonium salt 43b. Intramolecular Horner-Emmons reaction was used for synthesis of macrocyclization. Coupling of upper and bottom THP rings has been synthesized via Julia’s olefination of benzothiazole sulfone 136 and unsaturated aldehyde 212. The synthesis of 136 was achieved via diastereoselective differentiation to creat the $C_22$ quaternary asymmetric center. Synthetic route of 212 has been developed including asymmetric crotylation followed by a diastereoselective allylation, cyclization via Michael addition to form the two cis-2,6-disubstituted THP’s. For the synthesis maltophilin, a stereoselective synthesis of a tricyclic hydrocarbon subunit 336 has been studied. Mn(III)-based oxidative free radical cyclization of triolefinic β-ketoester was chosen for the synthesis of 336. An enantioselective synthetic route to β-ketoester has been developed via several crucial steps, including vinylation of unsaturated lactone, stereoselective alkylation, decarboxylation of cyanoacetate moiety, and aldol condensation. For the synthesis of acridinomycin A, tetronic acid derivative 421 and β-ketoester 423 was synthesized efficiently via coupling of 2-methyltetronate derivative 414and unsaturated lactone 274. Intramolecular Diels-Alder reaction was attempted to produce phenol 426 from furan moiety 427. With the prepared 2-acetoxyfuran 455, intermolecular Diels-Alder reaction with dienophile rac-259was accomplished to produce 456. But the preparation of diene 455 still remains improved.