The synthesis of a novel calcium ionophore on the model of pamamycin, an aerial mycelium-inducing factor of actinomyces.

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The three dimensional structure of pamamycin, classified as an armed macrocyclo compound, seemed to be a good model to develop a novel calcium ionophore. First of all, various synthetic macrolides were prepared from racemic homononactic acid obtained from alkaline hydrosis of polynactins. The 16-membered macrodiolides, which have an anti-relationship between the ether linkage of THF and the adjacent methyl, showed the cation-binding ability for Na^+ and Li^+. The compound may have a satisfactory basic structure in which this particular calcium ionophore might occur. Also this result made it necessary to synthesize an optically active compound in order to conformational analysis of a novel ionophore. Our synthetic study on optically active hydroxylic acid by use of asymmetric dihydroxylation reaction is undergoing. The synthetic study also contains the step of stereoselective construction of E-olefin for getting a highly enantiomeric pure compound. This problem was already overcome by the application of [2,3] -Wittig reaction, which gave not only E-olefin, but also Z-olefin. And the resulting compound has an allylsilane moiety which is very useful intermediate in organic synthesis. The investigation of the regio-and stereoselective introduction of side chain to macrolide was carried out with aldol reaction or alkylation for the synthesis of pamamycin related compounds. The aldol reaction with boron reagent gave high yields and the highest regio-and stereoselectivity. On the basis of these results, related studies on armed macrocyclo compound are under way, including development of a new guest for not only calcium cations but also other divalent cations.