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吗啡全合成

维基百科,自由的百科全书
吗啡

吗啡全合成是指化学中吗啡样生物碱的合成,描述了天然吗啡喃生物碱全合成,其包括可待因吗啡奥利平英语Oripavine,和蒂巴因及其密切相关的半合成类似物丁丙诺啡氢可酮异可待因英语Isocodeine纳曲酮英语Naltrexone纳洛酮纳布啡羟考酮[1][2]

吗啡的结构并不是特别复杂,然而,相邻结合原子的静电极化在整个结构中不均匀交替。这种“不一致的连接性”使得键的形成更加困难,并且因此使应用于该分子家族的任何合成策略明显的复杂化[2]

首次全合成由美國化學家马歇尔·D·盖茨于1952年完成,并被视为这个领域中的经典之作[3]。该合成总共用了31个步骤,并且总产率有0.06%。Kenner C. Rice的氢可酮合成是最有效的,用了14个步骤并且有30%的总产率[4]

此后,许多化学家提出了新的合成路线,其中值得注意的有以下研究者率领的团队所提出的路线:赖斯、[5]埃文斯、[6]富克斯、[7]帕克、[8]奥尔曼、[9]木泽尔·特劳纳、[10]怀特、[11]泰伯、[12]特罗斯特[13]福山[14]吉尤[15]斯托克[16]

盖茨的合成路线

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盖茨的吗啡全合成路线是在全合成中运用Diels-Alder反应的首个例子。

The Gates synthesis

Rice的合成路线

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Rice合成遵循仿生途径,并且是迄今为止已经被报道中最有效的。一个关键的步骤是Grewe环化,类似于发生在吗啡生物合成中的网状结构的环化 [4]

The Rice synthesis

参考文献

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  1. ^ Chida N. Recent advances in the synthesis of morphine and related alkaloids. Top Curr Chem. 2011, 299: 1–28. PMID 21630507. doi:10.1007/128_2010_73. 
  2. ^ 2.0 2.1 Rinner U, Hudlicky T. Synthesis of morphine alkaloids and derivatives. Top Curr Chem. 2012, 309: 33–66. PMID 21547687. doi:10.1007/128_2011_133. Morphine's synthesis remains a serious challenge to this day. 
  3. ^ Gates, Marshall; Tschudi, Gilg. Journal of the American Chemical Society. 1956, 78 (7): 1380. doi:10.1021/ja01588a033.  缺少或|title=为空 (帮助)
  4. ^ 4.0 4.1 Rice KC. Synthetic opium alkaloids and derivatives. A short total synthesis of (+/-)-dihydrothebainone, (+/-)-dihydrocodeinone, and (+/-)-nordihydrocodeinone as an approach to a practical synthesis of morphine, codeine, and congeners. The Journal of Organic Chemistry. July 1980, 45 (15): 3135–3137. doi:10.1021/jo01303a045. 
  5. ^ Rice, Kenner C. Synthetic opium alkaloids and derivatives. A short total synthesis of (.+-.)-dihydrothebainone, (.+-.)-dihydrocodeinone, and (.+-.)-nordihydrocodeinone as an approach to a practical synthesis of morphine, codeine, and congeners. The Journal of Organic Chemistry. 1980, 45 (15): 3135. doi:10.1021/jo01303a045. 
  6. ^ Evans, D.A.; Mitch, C.H. Studies directed towards the total synthesis of morphine alkaloids. Tetrahedron Letters. 1982, 23 (3): 285. doi:10.1016/S0040-4039(00)86810-0. 
  7. ^ Toth, J. E.; Hamann, P. R.; Fuchs, P. L. Studies culminating in the total synthesis of (dl)-morphine. The Journal of Organic Chemistry. 1988, 53 (20): 4694. doi:10.1021/jo00255a008. 
  8. ^ Parker, Kathlyn A.; Fokas, Demosthenes. Convergent synthesis of (.+-.)-dihydroisocodeine in 11 steps by the tandem radical cyclization strategy. A formal total synthesis of (.+-.)-morphine. Journal of the American Chemical Society. 1992, 114 (24): 9688. doi:10.1021/ja00050a075. 
  9. ^ Hong, Chang Y.; Kado, Noriyuki; Overman, Larry E. Asymmetric synthesis of either enantiomer of opium alkaloids and morphinans. Total synthesis of (-)- and (+)-dihydrocodeinone and (-)- and (+)-morphine. Journal of the American Chemical Society. 1993, 115 (23): 11028. doi:10.1021/ja00076a086. 
  10. ^ Mulzer, Johann; Dürner, Gerd; Trauner, Dirk. Formal Total Synthesis of(—)-Morphine by Cuprate Conjugate Addition. Angewandte Chemie International Edition in English. 1996, 35 (2324): 2830. doi:10.1002/anie.199628301. 
  11. ^ White, James D.; Hrnciar, Peter; Stappenbeck, Frank. Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid Insertion. The Journal of Organic Chemistry. 1999, 64 (21): 7871. doi:10.1021/jo990905z. 
  12. ^ Taber, Douglass F.; Neubert, Timothy D.; Rheingold, Arnold L. Synthesis of (−)-Morphine. Journal of the American Chemical Society. 2002, 124 (42): 12416–7. PMID 12381175. doi:10.1021/ja027882h. 
  13. ^ Trost, Barry M.; Tang, Weiping. Enantioselective Synthesis of (−)-Codeine and (−)-Morphine. Journal of the American Chemical Society. 2002, 124 (49): 14542–3. PMID 12465957. doi:10.1021/ja0283394. 
  14. ^ Uchida, Kenji; Yokoshima, Satoshi; Kan, Toshiyuki; Fukuyama, Tohru. Total Synthesis of (±)-Morphine. Organic Letters. 2006, 8 (23): 5311–3. PMID 17078705. doi:10.1021/ol062112m. 
  15. ^ Varin, Marie; Barré, Elvina; Iorga, Bogdan; Guillou, Catherine. Diastereoselective Total Synthesis of (±)-Codeine. Chemistry - A European Journal. 2008, 14 (22): 6606. doi:10.1002/chem.200800744. 
  16. ^ Stork, Gilbert; Yamashita, Ayako; Adams, Julian; Schulte, Gary R.; Chesworth, Richard; Miyazaki, Yoji; Farmer, Jay J. Regiospecific and Stereoselective Syntheses of (±) Morphine, Codeine, and Thebaine via a Highly Stereocontrolled Intramolecular 4 + 2 Cycloaddition Leading to a Phenanthrofuran System. Journal of the American Chemical Society. 2009, 131 (32): 11402–6. PMID 19624126. doi:10.1021/ja9038505. 

外部链接

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