Macrosphelide library, combinatorial synthesis

A combinatorial synthesis of macrosphelide analogs was carried out using a split-and-mix method using RF tags. Based upon 4 A units, 4 B units, and 8 C units, a 128-member library was possible (Scheme 10.11 and Scheme 10.13). The crude products obtained by cleavage from the polymer support were purified by automated reversed-phase preparative HPLC gave 122 products (0.2 to 1.5 mg from 30 mg of DHP resin 27) and included macrosphelides A, C, E, and F. 

Takahashi, T. et al., A combinatorial synthesis of a macrosphelide library utilizing a palladium-catalyzed carbonylation on a polymer support, Angew. Chem., Int. Ed. Engl, 42, 5230, 2003. 

Chemoselective carbonylation of a vinyl iodide 34 with alcohol containing a vinyl bromide moiety 35 has been successfully employed for the solid-phase synthesis of a macrosphelide precursor 36 [43]. After the 4-methoxyphenylmethyl (MPM) group was removed, the palladium-catalyzed carbonylative macrolactonization of the vinyl bromide 37 achieved the synthesis of the macrosphelide-supported derivative 38 (Scheme 9.13). The combinatorial synthesis of a 122-member macrosphelide library has been performed by the three-component strategy based on the palladium-catalyzed chemoselective carbonylation/macrolactonization reaction. 

Takahashi et al. have reported on a combinatorial synthesis of a library of 122 macrosphelides, which uses a three-component coupling in which not only the building blocks are connected by a Pd-catalyzed carbonylation, but also this reaction is used for macrocyclic ring closure on a solid support (Scheme 7) [101]. 

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