71 制癌性抗生物質ブレオマイシン各部位の合成とDNA切断分子の設計(口頭発表の部)

概要

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Bleomycins (BLMs) are a group of antitumor antibiotics of unusual glycopeptide structure. The potent activity of BLM is attributed to the oxygen activation and the DNA cleavage by the iron-chelate of the linear sequence of unique amino acids. The aldol reaction of (R)-3-bromoacetyl-4-isopropyl-1,3-oxazolidin-2-one 8 with 1-triphenylmehtylimidazole-4-carbaldehyde 9 proceeded highly enantioselectively to give bromohydrin 10 which was converted into erythro-β-hydroxy-L-histidine 2, a pivotal amino acid for the oxygen activation. (2S,3S,4R)-4-Amino-3-hydroxy-2-methylpentanoic acid 3, a linker between the oxygen activating site and the DNA binding site, has been prepared in a good yield by aldol reaction of aldehyde 13 and chiral boron enolate of 12 with no isolable stereoisomers. The present synthesis of 2 and 3 allowed us to access artificial peptides with catalytic activity to activate oxygen, epoxidize olefin, and cleave DNA, namely, PYML-1, -4, -6, and PYML(6)-bleomycin.
天然有機化合物討論会の論文
1988-09-26