Synthesis dactomelyne

In the synthesis presented here of Z-dactomelyn (1), three key radical steps permitted stereoselective construction of a bispyran skeleton with the development of halogen-substituted slereogenic centers. Starting from (-)-diethyl tartrate (2), the target compound was prepared in 26 steps with an overall yield of 0.04%. 

Examples of fused pyrans which can be obtained in a similar manner include 6-oxasteroids (95JCS(P1)1089) and bicyclic vinyl ethers (95CC1117), whilst a double radical cyclisation of 3-alkoxyacrylates features in a synthesis of 3Z-dactomelyne (95JA8017). 

During their synthesis of the Dactomelynes, Lee and co-workers employed sodium cyanoborohydride and titanium(IV) chloride95 to accomplish the regiose-lective cleavage of a benzylidene acetal [Scheme 3,57].%... 

Radical reactions have developed into indispensable methods in organic synthesis [1] and are often used as key steps in the construction of complex natural products. Impressive demonstrations are found in the following examples taken from the current literature the dactomelyne synthesis by Lee et al [2] the camptothecin synthesis by Curran et al., [3] and of (7)-deoxypancratistatin by Keck et al.,... 

The total synthesis of the marine natural product (5Z)-dactomelyne (1) requires the elaboration of the c -linked pyranopyran skeleton and the stereoselective introduction of halogen atoms on the tetrahydropyran rings. Lee et al. [2] solved this problem by using of )9-alkoxy-acrylates twice as radical acceptors (Scheme 1). 

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