Oxopolyene macrolide

Iterative two-directional chain elongation enables rapid construction of 1,3-polyols (Scheme 23). For example, the polyol substructure that appears in the oxopolyene macrolide (+)-roxaticin is available in nine steps from propane-1,3-diol upon three iterations of double carbonyl allylation [286]. Notably, high levels of catalyst-directed stereoselectivity are observed (For selected examples of catalyst directed diastereoselectivity, see [289-296]). Analogous 1,3-polyol syntheses via iterative homologation in one direction also are reported [297]. 

The last example in this section is the total synthesis of RK-397 (83) by Sammakia et al. [71]. RK-397 (83) is an oxopolyene macrolide, which was isolated from a strain of soil bacteria. This natural product presents several synthetic challenges, including particularly the installation of the highly sensitive polyene moiety. Sammakia and coworkers successfully tackled this obstacle through a selective alkene cross metathesis reaction at a late stage (Fig. 24). By screening a number of reaction conditions, they found that treatment of alkene (84) and 2,4,6-hexatrienal with Grubbs I catalyst smoothly afforded polyene product (85) in 72% yield as a 4 1 mixture of /Z isomers. 

---