寻找高效、立体选择性和实用的合成具有药用重要性的复杂有机化合物的方法，以两性霉素 B 的 C21-C37 片段的合成为例。
Search for highly efficient, stereoselective, and practical synthesis of complex organic compounds of medicinal importance as exemplified by the synthesis of the C21-C37 fragment of amphotericin B.
机构信息
Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084 (USA).
出版信息
Chemistry. 2013 Sep 23;19(39):12938-42. doi: 10.1002/chem.201302383. Epub 2013 Sep 3.
Abstract
Highly stereoselective: A highly efficient, stereoselective and practical synthesis of the C21-C37 fragment of amphotericin B was realized in 25 % overall yield in eight longest linear steps from commercially available ethyl (S)-3-hydroxybutyrate by using Fráter-Seebach alkylation, Brown crotylboration, Negishi coupling, Heck reaction, and Horner-Wadsworth-Emmons (HWE) olefination as key steps (see diagram).
摘要
高立体选择性
通过 Fráter-Seebach 烷基化、Brown 烯丙基硼化、Negishi 偶联、Heck 反应和 Horner-Wadsworth-Emmons（HWE）烯烃化为关键步骤，从商业可得的乙基（S）-3-羟基丁酸酯出发，以 25%的总收率在 8 步最长线性步骤中实现了两性霉素 B 的 C21-C37 片段的高效、立体选择性和实用合成（见示意图）。
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本文引用的文献
1
Total Synthesis of (+)-Ratjadone.
Angew Chem Int Ed Engl. 2000 Dec 1;39(23):4364-4366. doi: 10.1002/1521-3773(20001201)39:23<4364::AID-ANIE4364>3.0.CO;2-G.
2
Highly(≥98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability via 1-Halo-1-alkyne Hydroboration-Tandem Negishi-Suzuki Coupling or Organoborate Migratory Insertion Protocol.
Adv Synth Catal. 2011 Nov;353(16):2981-2987. doi: 10.1002/adsc.201100420.
3
Highly(≥98%) Selective Trisubstituted Alkene Synthesis of Wide Applicability via Fluoride-Promoted Pd-Catalyzed Cross-Coupling of Alkenylboranes.
Isr J Chem. 2010 Dec 1;50(5-6):696-701. doi: 10.1002/ijch.201000051.
4
Chiral synthesis via organoboranes. 7. Diastereoselective and enantioselective synthesis of erythro- and threo-.beta.-methylhomoallyl alcohols via enantiomeric (Z)- and (E)-crotylboranes.
J Am Chem Soc. 1986 Sep 1;108(19):5919-23. doi: 10.1021/ja00279a042.
5
Magical power of transition metals: past, present, and future (Nobel Lecture).
Angew Chem Int Ed Engl. 2011 Jul 18;50(30):6738-64. doi: 10.1002/anie.201101380. Epub 2011 Jun 29.
6
Highly selective synthesis of conjugated dienoic and trienoic esters via alkyne elementometalation-Pd-catalyzed cross-coupling.
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11344-9. doi: 10.1073/pnas.1105155108. Epub 2011 Jun 27.
7
Alkyne elementometalation-Pd-catalyzed cross-coupling. Toward synthesis of all conceivable types of acyclic alkenes in high yields, efficiently, selectively, economically, and safely: "green" way.
J Org Chem. 2010 May 21;75(10):3151-82. doi: 10.1021/jo1003218.
8
From nature to the laboratory and into the clinic.
Bioorg Med Chem. 2009 Mar 15;17(6):2290-303. doi: 10.1016/j.bmc.2008.10.089. Epub 2008 Nov 6.
9
Simple, efficient, and modular syntheses of polyene natural products via iterative cross-coupling.
J Am Chem Soc. 2008 Jan 16;130(2):466-8. doi: 10.1021/ja078129x.
10
Palladium complexes of N-heterocyclic carbenes as catalysts for cross-coupling reactions--a synthetic chemist's perspective.
Angew Chem Int Ed Engl. 2007;46(16):2768-813. doi: 10.1002/anie.200601663.
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