Diplodialide synthesis

Both the Mukaiyama and Bestmann syntheses of the macrocyclic lactone recifeiolide (18), isolated from Cephalosporium recifei, involve sp-carbon alkylation steps (Scheme 36), and Shenvi and Gerlach have synthesi diplodialides A (19) via a route that involved the. rp-carbon alkylation step shown in Scheme 37. 

The foregoing conditions were applied successfully in the synthesis of diplodialide A (175 Scheme 37). Since earlier studies had demonstrated that the sulfide-contraction conditions were not compatible with a,3-unsaturated thioamides, the 3-acetoxy precursor (173) was used instead. The intramolecular sulfide-contraction reaction successfully accomplished the cyclization to generate the P-keto lactone (174) in modest yields. Elimination of the acetoxy group yielded diplodialide A (175). 

The reagent (PPhj + CBr ) used to convert OH to Br is one which takes advantage of the affinity of phosphorus for oxygen. The other product is PhjPO. Reagent (11) has been used in a synthesis of the enzyme inhibitor diplodialide-A. 

The method of synthesis of macrolides by cyclization of w-hydroxycarboxylic acids has had its successes this year in the preparation of A26771B, carbomycin josamycin, and the diplodialides A and B. ° Well known activation techniques were applied in all cases, and the interest in these papers lies largely with the preliminary manipulations necessary to set up appropriately... 

Besides amides and ketones, also lactones with higher-membered rings are made available by telomerization. Tsuji and Mandai reported a simple synthesis of diplodialide B, a naturally occuring ten-membered lactone which shows interesting biological activity [7] (Equation 5). 

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