P-37 カルバペネム骨格の新規構築法(ポスター発表の部)

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概要

• 論文の詳細を見る

• Carbapenems have attracted much attention as new β-lactam antibiotics since the discovery of thienamycin (1) which has potent and broad-spectrum antibacterial activity. Furthermore, the report of 1β-methylcarbapenem 2, in which chemical and metabolic stability are improved, has given a great impetus. Intensive efforts have been devoted to the synthetic studies on carbapenems which are fascinating targets in addition to their antibacterial potency. In the course of our studies on the syntheses of carbapenems, We have found the following three synthetic methods for the carbapenem skeletons. Firstly, treatment of the novel 1,3-thiazinone intermediates 6, 12, and 18 with NaH or KOt-Bu in the presence of Ph_3P to form the carbapenem enolate with a extrusion of sulfur atom, followed by phosphorylation and addition-elimination with mercaptans 8a,b gave effectively 1β-methylcarbapenems 9a,b and 13 and 1β-(2-hydroxyethyl)carbapenem 19. Secondly, the novel α-ethoxyenoate intermediates 23-Z and 23-E were treated with NBS to cyclize in 5-endo-trigonal mode which was thought to be unfavorable in the Boldwin's rule, giving stereospecifically carbapenams 25a and 25b, respectively. Carbapenams 25 were converted to carbapenem 26 by treatment of CH_3COCl and NaI. Thirdly, generation of the acyliminum ion from chloride 31 by the aid of AgBF_4 underwent aza-Cope rearrangement followed by intramolecular Mannich reaction to give carbapenam 32. Carbapenam 32 was transformed into β-ketoester 33, which is an important intermediate in the synthesis of carbapenems.

• 天然有機化合物討論会の論文
• 1995-09-01

著者

• 堀川 袷志

  田辺製薬・拓新研

• 山中 武志

  田辺製薬・拓新研

• 大菊 鋼

  田辺製薬・拓新研

• 桜井 修

  田辺製薬・拓新研

• 高橋 政巳

  田辺製薬・拓新研

• 林 雅仁

  田辺製薬・拓新研

• 岩崎 為雄

  田辺製薬・拓新研

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