34 ブレオマイシン(BLM)の合成的研究

概要

論文の詳細を見る
Bleomycin (BLM) is an antitumor antibiotic clinically used in the chemotherapy of squamous cell carcinomas and malignant lymphomas. BLM is a glycopeptide and contains many unusual amino acids in its molecule. Recently unique mode of action of BLM has been revealed. For the strategy of the synthesis of BLM, we segmented the aglycon of BLM into three fragments: pyrimidoblamic acid [A], polyfunctional dipeptide [B] and tripeptide S [C]. The key intermediates to synthesize pyrimidoblamic acid are 3-amino-2-t-butoxycarbonyl-aminopropionamide (Boc-DAPA 1) and ethyl 6-chloro-2-formyl-5-methylpyrimidine-4-carboxylate (2). 1 was prepared from Boc-L-asparagine by Hoffmann degradation, protection by benzyloxycarbonyl group, esterification with diazomethane, treatment with ammonia and removal of the benzyloxycarbonyl group by catalytic hydrogenation. 2 was prepared from ethyl α-ethoxalylpropionate and diethoxyacetamidine followed by treatment with POCl_3. The side chain at the C-2 of the pyrimidine ring of [A] was formed by a C-2 unit addition to the Schiff base prepared from (1) and (2) by 1) malonic acid half ester or 2) vinyloxyborane method. Boc^α or Z^α-DNP^<im>-hydroxyhistidine and 4-amino-3-hydroxy-2-methylpentanoic acid methyl ester were coupled with EEDQ to give [B]. Tripeptide S [C] was prepared by DCC and active ester methods without any trouble. We are now preparing the aglycon of BLM from fragments of [A], [B] and [C].
天然有機化合物討論会の論文
1980-09-10

34 ブレオマイシン(BLM)の合成的研究

スポンサーリンク

概要

著者

関連論文

スポンサーリンク