Synthesis of nonactin (author's transl)]

Synthesis of Nonactin. The macrotetrolide antibiotic nonactin (I), containing four units of a C₁₀ hydroxy acid, has been synthesized starting from two adequately protected derivatives (III and IV) of nonactic acid (II). The 32-membered ring of the macrotetrolide is built up by a sequence of condensation and deprotection steps leading first to a product with two, and subsequently to one with four nonactic acid residues (VIII) which is then cyclized in the presence of Ag⁺-ions. Two reactions forming ester bonds have been developed to condense the hydroxy acids and to effect the final cyclization. In one the activation of the carboxyl group is achieved by conversion into the mixed anhydride with 2,4,6-trimethylbenzene sulfonyl chloride in pyridine. In the other the Ag⁺-ion induced reaction of a S-(2-pyridyl) hydroxy carbothioate is used to form the corresponding macrocyclic lactone. In the case of nonactin the ring closure is promoted by the coordinating effect of Ag⁺-ions present in the reaction mixture.