吴元鎏, 朱莉亚, 杨光中, 郑多楷, 邵国贤, 陈建民, 韩广甸, 金碧燕, 张云淮, 金秀范, 田慧珍, 吴惠筠. 前列腺素的研究Ⅰ 消旋前列腺素F_(2α)及其ω-乙基同系物的合成J. 药学学报, 1981, 16(5): 349-355.
引用本文: 吴元鎏, 朱莉亚, 杨光中, 郑多楷, 邵国贤, 陈建民, 韩广甸, 金碧燕, 张云淮, 金秀范, 田慧珍, 吴惠筠. 前列腺素的研究Ⅰ 消旋前列腺素F_(2α)及其ω-乙基同系物的合成J. 药学学报, 1981, 16(5): 349-355.
Wu Yuanliu, Zhu Liya, Yang Guangzhong, Zheng Duokai, Shao Guoxian, Ghen Jianmin, Han Guangdian , Jin Biyan Zhang Yunhuai, Jin Xiufan, Tian Huizhen , Wu Huiyun, . RESEARCHES ON PROSTANOIDS. Ⅰ. TOTAL SYNTHESIS OF DL-PROSTAGLANDIN F2α AND ITS ω-ETHYL ANALOGJ. Acta Pharmaceutica Sinica, 1981, 16(5): 349-355.
Citation: Wu Yuanliu, Zhu Liya, Yang Guangzhong, Zheng Duokai, Shao Guoxian, Ghen Jianmin, Han Guangdian , Jin Biyan Zhang Yunhuai, Jin Xiufan, Tian Huizhen , Wu Huiyun, . RESEARCHES ON PROSTANOIDS. Ⅰ. TOTAL SYNTHESIS OF DL-PROSTAGLANDIN F2α AND ITS ω-ETHYL ANALOGJ. Acta Pharmaceutica Sinica, 1981, 16(5): 349-355.

前列腺素的研究Ⅰ 消旋前列腺素F_(2α)及其ω-乙基同系物的合成

RESEARCHES ON PROSTANOIDS. Ⅰ. TOTAL SYNTHESIS OF DL-PROSTAGLANDIN F2α AND ITS ω-ETHYL ANALOG

  • 摘要: 本文对Corey合成光学活性PGF2α路线进行简化,合成了dl-PGF2α及dl-ω-乙基PGF2α,用Arbuzov反应合成2-氧庚烷磷酸二乙酯(7A)及2-氧壬烷磷酸二乙酯(7B)。用Moffatt氧化(DMSO,DGC,无水磷酸)将氢解物(5)氧化为醛(6),用过量二异丁基铝氢于-78°还原3′-醇(9Aα及9Bα),可将其γ-内酯还原为γ-内半缩醛,同时除去5-联苯甲酰基,生成中间体(10Aα)及(10Bα),再与溴化5-三苯鏻戊酸之Wittig试剂缩合得到dl-PGF2α(11A)及dl-ω-乙基PGF2α(11B).

     

    Abstract: A simplified version of Corey's synthesis of the dl-PGF2α and its ω-ethyl homolog wasreported. Diethyl 2-oxoheptylphosphonate (7A) and 2-oxononanylphosphonate (7B) were obtained through Arbuzov reaction in 70~80% yield by heating 1-bromoheptan-2-one and 1-bromononan-2-one respectively with triethylphosphite at 170~180 for 1 hr. Oxidation of 4-hydroxymethyl lactone (5) in mild acidic condition (DMSO, DCC in the presence of anhydrous H3PO4) furnished aldehyde (6), which was subjected to Wittig-Horner reaction with sodium salt of 7 in dichloromethane. Treatment of the resulting 8 with sodium borohydride in methanol yielded a ca. 1:1 mixture of 3'R and 3'S epimers 9. Treatment of 9 Aα and 9 Bα with an excess of diisobutyl aluminium hydride at -78° afforded the intermediates hemiacetal (10Aα)and (10Bα)in over 80% yield, which were further reacted with Wittig reagent derived from triphenylphosphonium pentanoic acid bromide in dimethylsulfoxide to give dl-PGF2α (11A) and to-ethyl-dlPGF2α (11B) in yields around 50%.

     

/

返回文章
返回