27 放線菌由来の抗HIV物質Bellenamine(口頭発表の部)

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A water-soluble basic antibiotic bellenamine produced by Streptomyces nashvillensis MD743-GF4 has a unique open-chain aldoaminal structure and D-β-lysine which has been first found as the natural amino acid. Bellenamine inhibits weakly the growth of some Gram-positive bacteria and has strong activity against human immunodeficiency virus (HIV). The absolute structure, (R)-N-aminomethyl-3,6-diaminohexanamide was confirmed by the total synthesis which was achieved by a modified Curtius procedure starting with D-β-lysine. Bis(N-Cbz)D-β-lysylglycine was converted to tris(N-Cbz)bellenamine through the acid azide. Removal of the protecting groups gave bellenamine. D-β-Lysine was synthesized from D-ornithine by the Arndt-Eistert homologation sequence. L-β-Lysyl, D- and L-lysyl congeners synthesized by a similar method, showed no antibacterial activities. In an acidic solution at 75℃, bellenamine was converted into D-β-lysinamide and a new cyclized compound, (R)-6-(3-aminopropyl)-1,3-diazacyclohexan-4-one. Bellenamine was produced in a synthetic medium containing D-galactose, dextrin, (NH_4)_2SO_4 and CaCO_3. The biosynthesis was studied by feeding ^<13>C and ^<15>N labeled precursors to the synthetic medium. The high incorporation of D-[1-^<13>C]β-lysine indicated that it is a direct intermediate. While, supplement of L-β-lysine repressed the productivity of bellenamine. [2-^<13>C]Glycine was well incorporated into CH_2 of the aldoaminal. All four nitrogens were derived from [^<15>NH_4]SO_4 in the synthetic medium, and the presence of L-lysine and glycine showed high incorporation of ^<15>N into CONH. The feeding experiments of ^<13>C labeled acetates suggested that the D-β-lysine moiety was derived from L-lysine by catalysis of a new 2,3-aminomutase, and L-lysine was biosynthesized from acetates via the TCA cycle and diaminopimelic acid pathway.
天然有機化合物討論会の論文
1992-09-10

27 放線菌由来の抗HIV物質Bellenamine(口頭発表の部)

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