Total synthesis of (+)-Lanomycin, enantioselective synthesis of taxol side chain, and synthetic approach to lasonolide A

Abstract

(+)-Lanomycin has been synthesized enantioselectively via the coupling of sulfone 33 with ketone 7 derived from alcohol 6. After acetylation of 37 with acetic anhydride in the presence of p-toluenesulfonic acid in benzene, reductive cleavage with sodium amalgam gave a separable mixture of desired (E,E,E)-triene 36 and (Z,E,E)-triene 39. Finally, (+)-lanomycin was obtained from alcohol derived from 36 and N-Boc glycine. 112, the precursor of taxol side chain was attained employing the iodocyclization of the diimidate of diol 118. 118 was prepared from D-mannitol and benzyl phosponium salt 119. N-benzoyl amide 134 prepared from 118 was converted into the oxazoline acid 112 via oxidative cleavage followed by sodium chlorite oxidation. Another precursor of taxol side chain, epoxide 86 was prepared from diol 158 with m-chloroperbenzoic acid followed by oxidative cleavage and oxidation. For the synthesis of lasonolide A 161 the required intermediate 247 and phosphonium salt 303 was synthesized. 247 was prepared from sulfone 245 derived from (S)-butanetriol and ester 254a. The synthesis of 254a was started from triol 190. The key intermediate 202 for 254a was prepared from alcohol 197 by treatment with benzaldehyde in the presence of p-toluenesulfonic acid in toluene. Iodocyclization of 211 followed by oxidative cleavage afforded tetrahydropyran ester 254a. The preparation of bottom half 270 was prepared from Nicolaou``s aldehyde by stereoselective crotylation, allylation, iodocyclization and Zhao``s modified Wittig reaction sequentially. Stille coupling of vinyliodide 270 with vinyl tin 310 using palladium acetate and triphenylarsine in DMF afforded 313, a precursor of phosphonium salt 303.