A facile and mild macrolactonization reaction of ω-hydroxy acids was developed based on the transesterification of benzotriazole esters. Treatment of ω-hydroxy acids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and 1-hydroxy benzotriazole (HOBT) in chloroform provided macrolactones in excellent yields. The reactions were performed under basic, neutral and acidic conditions using N,N-dimethylaminopyridine (DMAP), tetrabutylammonium tetrafluoroborate (TBABF(4)) and BF(3)·Et(2)O, respectively. A calcined hydrotalcite was also used instead of DMAP. Finally, to test the scope of the protocol in the synthesis of biologically relevant macrolactones, the total synthesis of Sansalvamide A was carried out.
Calcined Mg-Al Hydrotalcites x = 0.20, 0.27, 0.33 proved effective catalysts for the lactonization of 10, 12, 15, and 16 hydroxy acid benzotriazole esters to their correspondent macrolactones. This new methodology was used for the lactonization step in the synthesis of Sansalvamide A.
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