The asymmetric total synthesis of cladospolide D, a natural 12-membered macrolide antibiotic, has been accomplished in 12-steps. Sharpless asymmetric dihydroxylation, Grubb's cross metathesis, and Shiina lactonization have been employed as the key reactions for the installation of the desired stereocenter and the construction of the macrolactone framework. (C) 2016 Elsevier Ltd. All rights reserved.