Aplasmomycin synthesis

Another useful reagent for macrolactonization via mixed phosphoric anhydride is N,N- bis(2-oxo-3-oxazolidinyl)phosphordiamidic chloride (BOP-Cl, 64), which was used by Corey and coworkers [41] in the first synthesis of aplasmomycin (67), a novel boron-containing macrocyclic antibiotic. As shown in Scheme 21, the linear precursor 65 was treated with 3 equiv of BOP-Cl (64) and 7 equiv of triethylamine in dichloromethane at 23 °C for 6 h to give the dilactone 66 in 71% yield. 

MEM-Protected butyrolactone 282 is instrumental in the stereoselective synthesis of the C-12 to C-17 fragment of the antibiotic aplasmomycin (Scheme 39) [90]. The key steps are those that result in the formation of new asymmetric centers. Reduction of 283 with zinc borohy-dride gives the a /-alcohol 284a with 15 1 diastereoselectivity as the result of chelation-controlled addition of hydride to the carbonyl group. The isomers are separable at the stage of intermediate 285. A second hydride reduction of 286 at —78 °C affords the yw-alcohol 287... 

This reaction has a general application in the synthesis of compounds containing three contiguous oxygenated carbons and has been successfully applied to the preparation of diazonamide aplasmomycin, boromycin, taxol, etc. 

The total synthesis of the boron-containing macrolide antibiotic aplasmomycin is one of the major achievements of this year. ... 

The au rie2Si group is used to protect in the synthesis of morphine, methynoLide from D-glucose, C+)-Aplasmomycin, thromboxane B and lOa-homothrom-boxane A, prostaglandin t d in carbapenein synthesis.3u Ph,Si protects OH in the preparation of the optically pure TriF fragment of acyl tetronic acid... 

Nakata, T., Saito, K., and Oishi, T. (1986a) Synthetic studies on (+)-aplasmomycin. 1. Stereoselective synthesis of the C12-C17 segment Tetrahedron Lett., 27, 6341-6344. 

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