Synthesis of the DEF-Ring Spirocyclic Core of Cyclopamine

被引：2

作者：

Shao, Hao ^{[1
]}

Liu, Wenheng ^{[1
]}

Fang, Zhengqi ^{[1
]}

He, Haibing ^{[1
,2
]}

Gao, Shuanhu ^{[1
,2
]}

机构：

[1] East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, State Key Lab Petr Mol & Proc Engn, Shanghai 200062, Peoples R China

[2] East China Normal Univ, Wuhu Hosp, Sch Chem & Mol Engn, Shanghai Frontiers Sci Ctr Mol Intelligent Synth, Shanghai 200062, Peoples R China

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2024年 / 89卷 / 06期

基金：

中国国家自然科学基金;

关键词：

VERATRUM ALKALOID SERIES; DIELS-ALDER REACTIONS; HEDGEHOG PATHWAY; VINYLOGOUS MANNICH; ASYMMETRIC-SYNTHESIS; MEDULLOBLASTOMA; DEAROMATIZATION; DERIVATIVES; CONVERGENT; EFFICIENT;

D O I：

10.1021/acs.joc.3c02804

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A stereoselective synthesis of the DEF-ring spirocyclic core of cyclopamine was accomplished using commercially available materials. The key steps in the synthesis were (i) the enantioselective vinylogous Mannich reaction, followed by lactamization to generate the piperidine F ring, and (ii) intramolecular oxidative dearomative spiroetherification to construct the DEF-ring spirocyclic core of cyclopamine. We found that the stereochemistry of the spirocyclization was controlled by the configuration of the methyl group (C-20) in the substrate.

引用

页码：4215 / 4220

页数：6

共 59 条

[1] Development of a Multi Kilogram-Scale, Tandem Cyclopropanation Ring-Expansion Reaction en Route to Hedgehog Antagonist IPI-926
Austad, Brian C.
Hague, Andrew B.
White, Priscilla
Peluso, Stephane
Nair, Somarajan J.
Depew, Kristopher M.
Grogan, Michael J.
Charette, Andre B.
Yu, Lin-Chen
Lory, Caroline D.
Grenier, Louis
Lescarbeau, Andre
Lane, Benjamin S.
Lombardy, Richard
Behnke, Mark L.
Koney, Nii
Porter, James R.
Campbell, Matthew J.
Shaffer, Jeanne
Xiong, Jimin
Helble, Joseph C.
Foley, Michael A.
Adams, Julian
Castro, Alfredo C.
Tremblay, Martin R.
[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2016, 20 (04) : 786 - 798
[2] (BDP)CuH: A "hot" Stryker's reagent for use in achiral conjugate reductions
Baker, Benjamin A.
Bokovic, Zarko V.
Lipshutz, Bruce H.
[J]. ORGANIC LETTERS, 2008, 10 (02) : 289 - 292
[3] The Hedgehog signaling pathway as a target for anticancer drug discovery
Borzillo, GV
Lippa, B
[J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2005, 5 (02) : 147 - 157
[4] A highly efficient and practical method for catalytic asymmetric vinylogous Mannich (AVM) reactions
Carswell, Emma L.
Snapper, Marc L.
Hoveyda, Amir H.
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (43) : 7230 - 7233
[5] Enantioselective Total Synthesis of (+)-Heilonine
Cassaidy, Kyle J.
Rawal, Viresh H.
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2021, 143 (40) : 16394 - 16400
[6] Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened
Chen, JK
Taipale, J
Cooper, MK
Beachy, PA
[J]. GENES & DEVELOPMENT, 2002, 16 (21) : 2743 - 2748
[7] Asymmetric total synthesis of norzoanthamine and formal synthesis of zoanthenol
Chen, Yanyu
Xin, Zhengyuan
Wang, Hui
He, Haibing
Gao, Shuanhu
[J]. ORGANIC CHEMISTRY FRONTIERS, 2023, 10 (03): : 651 - 660
[8] Patidegib in Dermatology: A Current Review
Cosio, Terenzio
Di Prete, Monia
Di Raimondo, Cosimo
Garofalo, Virginia
Lozzi, Flavia
Lanna, Caterina
Dika, Emi
Orlandi, Augusto
Rapanotti, Maria Cristina
Bianchi, Luca
Campione, Elena
[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (19)
[9] The hedgehog pathway and neurological disorders
Dellovade, Tammy
Romer, Justyna T.
Curran, Tom
Rubin, Lee L.
[J]. ANNUAL REVIEW OF NEUROSCIENCE, 2006, 29 : 539 - 563
[10] New synthesis of spirocycles by utilizing in situ forming hypervalent iodine species
Dohi, Toshifumi
Nakae, Tomofumi
Ishikado, Yohei
Kato, Daishi
Kita, Yasuyuki
[J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2011, 9 (20) : 6899 - 6902

← 1 2 3 4 5 6 →