Synthesen der Nonactinsäure

Abstract Two stereoselective syntheses of nonactic acid I, the building block of the macrotetrolide antibiotic nonactin are described. The characteristic cis ‐configuration of the 2,5‐substituents on the tetrahydrofuran ring of I is obtained in the first synthesis by catalytic hydrogenation of the furan derivative X. This key intermediate possesses the carbon skeleton and correct distribution of oxygen functions for conversin into nonactic acid. It is synthesized by an electrophilic substitution of 2‐acetonylfuran (VI) with the N‐cyclohexyl‐N‐propenyl nitrosonium ion (V) generated from the corresponding α‐chloronitrone (VII) and silver fluoroborate, followed by hydrolysis and oxidation of the aldehyde group. The second synthesis starts with a diol already having the correct configuration of the side chain that contains the hydroxyl group. For this purpose threo ‐1‐octen‐5,7‐diol (XV) is synthesized from acetylacetone in two steps. Oxidative cleavage of the terminal double bond of this threo ‐diol yields an aldehyde which is converted by a Wittig reaction, with the carbanion, obtained from diethyl α‐methoxycarbonylethyl phosphonate, into the open chain intermediate, 2‐methyl‐6,8‐dihydroxy‐2‐nonenoic acid methylester (XVIII). Base‐catalyzed cyclisation of this α,β‐unsaturated dihydroxy ester yields the methyl ester of nonactic acid (I) as the main product.