用于合成新型蛋白酶抑制剂的结构单元——制备叔丁基-2-(3,5-二氟苯基)-1-(环氧乙烷-2-基)乙基氨基甲酸酯的高立体选择性不对称羟醛缩合路线
Highly Stereoselective Asymmetric Aldol Routes to -Butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building Blocks for Novel Protease Inhibitors.
作者信息
Ghosh Arun K, Cárdenas Emilio L, Brindisi Margherita
机构信息
Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
出版信息
Tetrahedron Lett. 2017 Oct 25;58(43):4062-4065. doi: 10.1016/j.tetlet.2017.09.025. Epub 2017 Sep 14.
Abstract
Enantioselective syntheses of -butyl (()-2-(3,5-difluorophenyl)-1-(()-oxiran-2-yl)ethyl)carbamate and (()-2-(3,5-difluorophenyl)-1-(()-oxiran-2-yl)ethyl)carbamate are described. We utilized asymmetric - and -aldol reactions to set both stereogenic centers. We investigated ester-derived Ti-enolate aldol reactions as well as Evans' diastereoselective -aldol reaction for these syntheses. We have converted optically active (()-2-(3,5-difluorophenyl)-1-(()-oxiran-2-yl)ethyl)carbamate to a potent β-secretase inhibitor.
摘要
描述了（）-丁基（（）-2-（3,5-二氟苯基）-1-（（）-环氧乙烷-2-基）乙基）氨基甲酸酯和（（）-2-（3,5-二氟苯基）-1-（（）-环氧乙烷-2-基）乙基）氨基甲酸酯的对映选择性合成。我们利用不对称α-和β-羟醛缩合反应来构建两个手性中心。我们研究了酯衍生的钛烯醇盐羟醛缩合反应以及埃文斯非对映选择性β-羟醛缩合反应用于这些合成。我们已将光学活性的（（）-2-（3,5-二氟苯基）-1-（（）-环氧乙烷-2-基）乙基）氨基甲酸酯转化为一种有效的β-分泌酶抑制剂。
相似文献
1
Highly Stereoselective Asymmetric Aldol Routes to -Butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building Blocks for Novel Protease Inhibitors.用于合成新型蛋白酶抑制剂的结构单元——制备叔丁基-2-(3,5-二氟苯基)-1-(环氧乙烷-2-基)乙基氨基甲酸酯的高立体选择性不对称羟醛缩合路线
Tetrahedron Lett. 2017 Oct 25;58(43):4062-4065. doi: 10.1016/j.tetlet.2017.09.025. Epub 2017 Sep 14.
2
Transition-State Mimetics for HIV Protease Inhibitors: Stereocontrolled Synthesis of Hydroxyethylene and Hydroxyethylamine Isosteres by Ester-Derived Titanium Enolate Syn and Anti-Aldol Reactions.用于HIV蛋白酶抑制剂的过渡态模拟物：通过酯衍生的钛烯醇盐顺式和反式羟醛缩合反应立体控制合成羟乙烯和羟乙胺电子等排体
J Org Chem. 1998 Sep 4;63(18):6146-6152. doi: 10.1021/jo980159i.
3
[Development of highly stereoselective reactions utilizing heteroatoms--asymmetric synthesis of alpha-substituted serines].[利用杂原子的高立体选择性反应——α-取代丝氨酸的不对称合成]
Yakugaku Zasshi. 2000 Jan;120(1):28-41. doi: 10.1248/yakushi1947.120.1_28.
4
Asymmetric synthesis of chiral organofluorine compounds: use of nonracemic fluoroiodoacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors.手性有机氟化合物的不对称合成：使用非外消旋氟碘乙酸作为实用亲电试剂及其在新型HIV蛋白酶抑制剂系列中一氟代羟基乙烯二肽类似物合成中的应用。
J Am Chem Soc. 2001 Aug 1;123(30):7207-19. doi: 10.1021/ja010113y.
5
Regulated-stereoselective construction of thirteen stereogenic centers necessary for the frame of (+)-discodermolide, based on iterative Lewis acid-promoted aldol reactions.基于迭代路易斯酸促进的羟醛反应，对（+）-盘状海绵醇骨架所需的13个立体中心进行立体选择性构建。
J Org Chem. 2003 Oct 17;68(21):7967-78. doi: 10.1021/jo034901c.
6
Samarium Ion-Promoted Cross-Aldol Reactions and Tandem Aldol/Evans-Tishchenko Reactions.钐离子促进的交叉羟醛缩合反应及串联羟醛缩合/埃文斯-蒂申科反应
J Org Chem. 1999 Feb 5;64(3):843-853. doi: 10.1021/jo981675b.
7
syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic acid derivatives catalyzed by an axially chiral amino sulfonamide.轴手性氨基磺酰胺催化的醛与乙醛酸衍生物的 syn-选择性不对称交叉羟醛反应。
Chem Commun (Camb). 2011 Oct 14;47(38):10626-8. doi: 10.1039/c1cc14347f. Epub 2011 Sep 5.
8
A systematic study of the effects of relative configuration, protecting group, and enolate type on the diastereoselectivities of aldol reactions of a chiral ethyl ketone with 2-methylpropanal.关于手性乙基酮与2-甲基丙醛的羟醛缩合反应中相对构型、保护基和烯醇盐类型对非对映选择性影响的系统研究。
J Org Chem. 2014 Aug 1;79(15):6868-94. doi: 10.1021/jo500927x. Epub 2014 Jul 16.
9
Stereoselective chloroacetate aldol reactions: syntheses of acetate aldol equivalents and darzens glycidic esters.立体选择性氯乙酸酯羟醛缩合反应：乙酸酯羟醛等价物和达森缩水甘油酸酯的合成
Org Lett. 2004 Aug 5;6(16):2725-8. doi: 10.1021/ol0490835.
10
The Total Synthesis of Inostamycin A.Inostamycin A 的全合成。
Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2573-6. doi: 10.1002/anie.201510852. Epub 2016 Jan 22.
引用本文的文献
1
Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance.超越达芦那韦：新一代 HIV-1 蛋白酶抑制剂抵抗耐药性的最新进展。
Chem Commun (Camb). 2022 Oct 20;58(84):11762-11782. doi: 10.1039/d2cc04541a.
2
Regioselective Cross-Electrophile Coupling of Epoxides and (Hetero)aryl Iodides via Ni/Ti/Photoredox Catalysis.通过镍/钛/光氧化还原催化实现环氧化物与（杂）芳基碘化物的区域选择性交叉亲电偶联反应。
ACS Catal. 2020 May 15;10(10):5821-5827. doi: 10.1021/acscatal.0c01199. Epub 2020 May 4.
3
Nature Inspired Molecular Design: Stereoselective Synthesis of Bicyclic and Polycyclic Ethers for Potent HIV-1 Protease Inhibitors.受自然启发的分子设计：用于高效HIV-1蛋白酶抑制剂的双环和多环醚的立体选择性合成
Asian J Org Chem. 2018 Aug;7(8):1448-1466. doi: 10.1002/ajoc.201800255. Epub 2018 Jun 8.
4
The Curtius Rearrangement: Applications in Modern Drug Discovery and Medicinal Chemistry.库尔提乌斯重排反应：在现代药物发现和药物化学中的应用。
ChemMedChem. 2018 Nov 20;13(22):2351-2373. doi: 10.1002/cmdc.201800518. Epub 2018 Oct 11.
本文引用的文献
1
Synthesis of Bioactive Natural Products by Asymmetric - and -Aldol Reactions.通过不对称羟醛缩合反应合成生物活性天然产物
Synthesis (Stuttg). 2009 Sep;2009(17):2992-3002. doi: 10.1055/s-0029-1216941.
2
Syntheses of FDA Approved HIV Protease Inhibitors.美国食品药品监督管理局批准的HIV蛋白酶抑制剂的合成
Synthesis (Stuttg). 2001;2001(15):2203-2229. doi: 10.1055/s-2001-18434.
3
Synthesis of Enantiomerically Pure Anti-Aldols: A Highly Stereoselective Ester-Derived Titanium Enolate Aldol Reaction.对映体纯的反式醛醇缩合物的合成：一种高度立体选择性的酯衍生钛烯醇盐醛醇缩合反应。
J Am Chem Soc. 1996 Mar 13;118(10):2527-2528. doi: 10.1021/ja9539148.
4
Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS.用于治疗艾滋病毒/艾滋病的HIV-1蛋白酶抑制剂开发的最新进展
J Med Chem. 2016 Jun 9;59(11):5172-208. doi: 10.1021/acs.jmedchem.5b01697. Epub 2016 Jan 22.
5
Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer's Disease.β-分泌酶抑制剂治疗阿尔茨海默病的前景
ChemMedChem. 2015 Sep;10(9):1463-6. doi: 10.1002/cmdc.201500216. Epub 2015 Jul 3.
6
BACE1 inhibitor drugs in clinical trials for Alzheimer's disease.用于阿尔茨海默病临床试验的β-分泌酶1（BACE1）抑制剂药物。
Alzheimers Res Ther. 2014 Dec 24;6(9):89. doi: 10.1186/s13195-014-0089-7. eCollection 2014.
7
BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease.用于治疗阿尔茨海默病的β-分泌酶1（BACE1）抑制剂。
Chem Soc Rev. 2014 Oct 7;43(19):6765-813. doi: 10.1039/c3cs60460h.
8
Developing β-secretase inhibitors for treatment of Alzheimer's disease.开发β-分泌酶抑制剂治疗阿尔茨海默病。
J Neurochem. 2012 Jan;120 Suppl 1(Suppl 1):71-83. doi: 10.1111/j.1471-4159.2011.07476.x. Epub 2011 Nov 28.
9
The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential.健康与阿尔茨海默病中的β-分泌酶BACE：调控、细胞生物学、功能及治疗潜力
J Neurosci. 2009 Oct 14;29(41):12787-94. doi: 10.1523/JNEUROSCI.3657-09.2009.
10
Memapsin 2 (beta-secretase) inhibitor drug, between fantasy and reality.膜内天冬氨酸蛋白酶2（β-分泌酶）抑制剂药物，介于幻想与现实之间。
Curr Alzheimer Res. 2007 Sep;4(4):418-22. doi: 10.2174/156720507781788864.
Zotero 插件