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嗎啡全合成

維基百科,自由的百科全書
嗎啡

嗎啡全合成是指化學中嗎啡樣生物鹼的合成,描述了天然嗎啡喃生物鹼全合成,其包括可待因嗎啡奧利平英語Oripavine,和蒂巴因及其密切相關的半合成類似物丁丙諾啡氫可酮異可待因英語Isocodeine納曲酮英語Naltrexone納洛酮納布啡羥考酮[1][2]

嗎啡的結構並不是特別複雜,然而,相鄰結合原子的靜電極化在整個結構中不均勻交替。這種「不一致的連接性」使得鍵的形成更加困難,並且因此使應用於該分子家族的任何合成策略明顯的複雜化[2]

首次全合成由美國化學家馬歇爾·D·蓋茨於1952年完成,並被視為這個領域中的經典之作[3]。該合成總共用了31個步驟,並且總產率有0.06%。Kenner C. Rice的氫可酮合成是最有效的,用了14個步驟並且有30%的總產率[4]

此後,許多化學家提出了新的合成路線,其中值得注意的有以下研究者率領的團隊所提出的路線:賴斯、[5]埃文斯、[6]富克斯、[7]帕克、[8]奧爾曼、[9]木澤爾·特勞納、[10]懷特、[11]泰伯、[12]特羅斯特[13]福山[14]吉尤[15]斯托克[16]

蓋茨的合成路線

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蓋茨的嗎啡全合成路線是在全合成中運用Diels-Alder反應的首個例子。

The Gates synthesis

Rice的合成路線

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Rice合成遵循仿生途徑,並且是迄今為止已經被報道中最有效的。一個關鍵的步驟是Grewe環化,類似於發生在嗎啡生物合成中的網狀結構的環化 [4]

The Rice synthesis

參考文獻

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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=為空 (幫助)
  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. 

外部連結

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