Synthesis of (+)-lactacystin 1 was accomplished in two different pathways. In the first approach, an enantioselective synthetic route to (+)-lactacystin 1 has been developed via several crucial steps, including amino hydroxylation of olefinic double bond in 116, the hydrolytic cyclization of 123, and regio- and stereo-selective functionalization of one hydroxymethyl group in 47. In the second approach, the synthetic route to (+)-lactacystin 1 has been established via several enantioselective steps, which culminated in diastereoselective crotylboration of 137c and hydroxy amination of allylic trichloroacetimidate 146 using mercurioamidation.
For the synthesis of trichodimerol 159, a stereoselective synthetic route to an 8-membered ring 305, as a key intermediate, has been established. Fragmentation of bicyclo[3.3.1]nonane system has been developed to construct 8-membered carbocycle 305, which was achieved via asymmetric epoxidation followed by regioselective opening of 183 and dimerization of 311.
For the synthesis of lasonolide A 318, a macrocyclic lactone 445 was synthesized efficiently via coupling of benzothiazol sulfone 447 and Z-α, β-unsaturated aldehyde 439. Benzothiazol sulfone 447 has been synthesized via iodocyclization of 347, Julia-type coupling of 404 and 405, and functionalization of hydroxyl group in 410. The synthesis of aldehyde 439 was achieved via an asymmetric crotylation followed by a diastereoselective allylation of 389, anionic cyclization of 393, and formation of Z-α, β-unsaturated ester 398.