Enantioselective Total Synthesis of ()-Candelalides A, B and C: Potential Kv1.3 Blocking Immunosuppressive Agents

摘要

Novel Kv1.3 blocking immunosuppressants,()-candelalides A, B and C, were efficiently synthesized for the first time in a convergent and unified manner starting from (+)-5-methyl-WielandCMiescher ketone. The synthetic method involved the following key steps: i) a strategic [2,3]-Wittig rearrangement of a stannylmethyl ether to install the stereogenic center at C9 and the exo-methylene function at C8 present in the decalin portion; ii)a straightforward coupling of a transdecalin portion (BC ring) and a gpyrone moiety through the C16C3bond to assemble the requisite carbon framework; and iii) a construction of a characteristic di or tetrahydropyran ring (A ring) by internal nucleophilic ring closure of a hydroxy aldehyde or a hydroxy epoxide. The present total synthesis has fully established the absolute configuration of these natural products.