Highly Stereodivergent Synthesis of Chiral C4-Ester-Quaternary Pyrrolidines: A Strategy for the Total Synthesis of Spirotryprostatin A

被引：33

作者：

Chen, Zhigang ^{[1
]}

Zhong, Wei ^{[1
]}

Liu, Sihua ^{[1
]}

Zou, Ting ^{[1
]}

Zhang, Kaiqiang ^{[2
,3
]}

Gong, Chuliang ^{[1
]}

Guo, Wenyan ^{[1
]}

Kong, Feizhi ^{[1
]}

Nie, Libo ^{[1
]}

Hu, Shunqin ^{[1
]}

Wang, Haifei ^{[1
]}

机构：

[1] Hunan Univ Technol, Coll Life Sci & Chem, Zhuzhou 412007, Hunan, Peoples R China

[2] Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Fujian, Peoples R China

[3] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Fujian, Peoples R China

来源：

ORGANIC LETTERS | 2023年 / 25卷 / 19期

基金：

中国国家自然科学基金;

关键词：

ENANTIOSELECTIVE 1,3-DIPOLAR CYCLOADDITION; ASYMMETRIC TOTAL-SYNTHESIS; AZOMETHINE YLIDES; CONCISE; ACID; CONSTRUCTION; DERIVATIVES; CATALYSTS;

D O I：

10.1021/acs.orglett.3c00904

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

In this work, we disclose two sets of highly diastereo-and enantioselective [3 + 2] cycloadditions of iminoesters with various alpha-substituted acrylates, especially for sterically hindered and weakly activated alpha-aryl or alkyl-substituted acrylates and alkenal, alkynal, or unstable aliphatic aldehyde-derived iminoesters, catalyzed by the AgHMDS/DTBM-Segphos or Ag2O/ CA-AA-Amidphos catalytic system, achieving the stereodivergent synthesis of chiral C4-ester-quaternary exo-or endo-pyrrolidines with high yields and excellent diastereo-and enantioselectivities (up to >99:1 dr and >99% ee). More importantly, the gram-scale synthetic exo-adduct displays significant applications in the aspect of realizing the total synthesis of the spirotryprostatin A alkaloid via nine steps in a 36% overall yield.

引用

页码：3391 / 3396

页数：6

共 39 条

[1] Stereochemical diversity in pyrrolidine synthesis by catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides [J].

Adrio, Javier ;

Carretero, Juan C. .

CHEMICAL COMMUNICATIONS, 2019, 55 (80) :11979-11991

[2] Recent advances in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides [J].

Adrio, Javier ;

Carretero, Juan C. .

CHEMICAL COMMUNICATIONS, 2014, 50 (83) :12434-12446

[3] Novel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides [J].

Adrio, Javier ;

Carretero, Juan C. .

CHEMICAL COMMUNICATIONS, 2011, 47 (24) :6784-6794

[4] Stereoselective synthesis and applications of spirocyclic oxindoles [J].

Boddy, Alexander J. ;

Bull, James A. .

ORGANIC CHEMISTRY FRONTIERS, 2021, 8 (05) :1026-1084

[5] Asymmetic Organocatalytic 1,3-Dipolar Cycloaddition of Azomethine Ylide to Methyl 2-(2-Nitrophenyl)acrylate for the Synthesis of Diastereoisomers of Spirotryprostatin A [J].

Chang, Mou-Nuo ;

Wang, Hao ;

Gong, Liu-Zhu .

ORGANIC LETTERS, 2011, 13 (09) :2418-2421

[6] Chiral Trifluoromethylated Pyrrolidines via Cu-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition [J].

Cheng, Xiang ;

Yan, Dingce ;

Dong, Xiu-Qin ;

Wang, Chun-Jiang .

ASIAN JOURNAL OF ORGANIC CHEMISTRY, 2020, 9 (10) :1567-1570

[7] Novel mammalian cell cycle inhibitors, spirotryprostatins A and B, produced by Aspergillus fumigatus, which inhibit mammalian cell cycle at G2/M phase [J].

Cui, CB ;

Kakeya, H ;

Osada, H .

TETRAHEDRON, 1996, 52 (39) :12651-12666

[8] Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues [J].

Edmondson, S ;

Danishefsky, SJ ;

Sepp-Lorenzino, L ;

Rosen, N .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (10) :2147-2155

[9]

Edmondson SD, 1998, ANGEW CHEM INT EDIT, V37, P1138, DOI 10.1002/(SICI)1521-3773(19980504)37:8<1138::AID-ANIE1138>3.0.CO

[10]

2-N

← 1 2 3 4 →