Synthesis of Sominone and Its Derivatives Based on an RCM Strategy: Discovery of A Novel Anti-Alzheimer’s Disease Medicine Candidate “Denosomin”Click to copy article linkArticle link copied!
Abstract

Synthesis of sominone was achieved starting from dehydroepiandrosterone on the basis of an RCM strategy for the construction of a δ-lactone side chain. This synthetic protocol was applied for the synthesis of several analogous derivatives including 1-deoxy-24-norsominone (denosomin), which was revealed to exhibit notable bioactivities for new antidementia chemotherapy, exceeding the original natural compound sominone.
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- Oleksandr Vyhivskyi, Olivier Baudoin. Total Synthesis of the Diterpenes (+)-Randainin D and (+)-Barekoxide via Photoredox-Catalyzed Deoxygenative Allylation. Journal of the American Chemical Society 2024, 146
(16)
, 11486-11492. https://doi.org/10.1021/jacs.4c02224
- Hidetaka Kuroiwa, Soichiro Suzuki, Kazuhiro Irie, Chihiro Tsukano. Total Synthesis and Structure Revision of (+)-Lancilactone C. Journal of the American Chemical Society 2023, 145
(27)
, 14587-14591. https://doi.org/10.1021/jacs.3c04124
- Jiahui Lin, Zihao Zhu, Yuwen Chen, Zhiyuan Ma, Weiwei Zuo, Meifang Zhu. Synthesis and Cytotoxicity Evaluation of Betulin Cycloolefin Derivatives by Ruthenium-Catalyzed Ring-Closing Metathesis. Journal of Natural Products 2023, 86
(4)
, 842-849. https://doi.org/10.1021/acs.jnatprod.2c01019
- Kai Tan, Huan Yan, Pengbo Lu, Yuehui Liu, Ruigeng Ji, Zhongxian Liu, Ya-Min Li, Fu-Chao Yu, Yuehai Shen. Access to Multisubstituted 2(5H)-Furanones Using Hydrogen Bonding-Promoted Ring-Closing Metathesis and Polyamine Workup. The Journal of Organic Chemistry 2019, 84
(6)
, 3419-3430. https://doi.org/10.1021/acs.joc.8b03293
- Tao Zhou, Feng Feng, Yong Shi, and Wei-Sheng Tian . Synthesis Toward and Stereochemical Assignment of Clathsterol: Exploring Diverse Strategies to Polyoxygenated Sterols. Organic Letters 2016, 18
(9)
, 2308-2311. https://doi.org/10.1021/acs.orglett.6b01029
- Kenji Sugimoto, Hisanari Yajima, Yusuke Hayashi, Daishiro Minato, Sayuri Terasaki, Chihiro Tohda, and Yuji Matsuya . Synthesis of Denosomin–Vitamin D3 Hybrids and Evaluation of Their Anti-Alzheimer’s Disease Activities. Organic Letters 2015, 17
(23)
, 5910-5913. https://doi.org/10.1021/acs.orglett.5b03138
- Bapurao B. Shingate and Braja G. Hazra . A Concise Account of Various Approaches for Stereoselective Construction of the C-20(H) Stereogenic Center in Steroid Side Chain. Chemical Reviews 2014, 114
(12)
, 6349-6382. https://doi.org/10.1021/cr4004083
- Chitikela P Pullaiah, Preethi Priyadharshini SP, Phareedha SK, Yamini Nemalapalli, Geetha Birudala, S Lahari, Shanmugam Vippamakula, R Shakila, Muni Swamy Ganjayi, Raghavendra Mitta. Exploring Withanolides from Withania somnifera: A Promising Avenue for Alzheimer’s Disease Treatment. Current Pharmacology Reports 2025, 11
(1)
https://doi.org/10.1007/s40495-025-00394-2
- Wen Che, Lukasz Wojitas, Chuan Shan, Justin M. Lopchuk. Divergent synthesis of complex withanolides enabled by a scalable route and late-stage functionalization. Science Advances 2024, 10
(26)
https://doi.org/10.1126/sciadv.adp9375
- Tomoharu Kuboyama, Ximeng Yang, Chihiro Tohda. Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer’s Disease. International Journal of Molecular Sciences 2020, 21
(13)
, 4665. https://doi.org/10.3390/ijms21134665
- Pengbo Lu, Zhongxian Liu, Yuehai Shen. Synergic effect of hydrogen bonding and dipole repulsion in the ring-closing metathesis of N-homoallyl-2-(hydroxymethyl)acrylamides. Tetrahedron Letters 2019, 60
(27)
, 1808-1810. https://doi.org/10.1016/j.tetlet.2019.06.011
- Shao-Rui Chen, Hao Wu, Hai-Yan Zhao, Yu-Mei Zhang, Peng-Qi Li, Lian-Mei Zhao. Synthesis and antiproliferative activity of novel 4-azasteroidal-17-hydrazone derivatives. Journal of Chemical Research 2019, 43
(3-4)
, 130-134. https://doi.org/10.1177/1747519819851706
- C. Lecourt, S. Dhambri, L. Allievi, Y. Sanogo, N. Zeghbib, R. Ben Othman, M.-I. Lannou, G. Sorin, J. Ardisson. Natural products and ring-closing metathesis: synthesis of sterically congested olefins. Natural Product Reports 2018, 35
(1)
, 105-124. https://doi.org/10.1039/C7NP00048K
- Shuo-En Tsai, Jang-Chang Lee, Naoto Uramaru, Hiroyuki Takayama, Guan-Jhong Huang, Fung Fuh Wong. Synthesis and antiproliferative activity of 3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-one with a C-21 hydrophilic substituent. Heteroatom Chemistry 2017, 28
(3)
, e21372. https://doi.org/10.1002/hc.21372
- Gurcharan Kaur, Taranjeet Kaur, Muskan Gupta, Shaffi Manchanda. Neuromodulatory Role of Withania somnifera. 2017, 417-436. https://doi.org/10.1007/978-3-319-59192-6_20
- Shijun Zhang, John M. Saathoff, Liu He. Molecular Hybridization. 2017, 219-237. https://doi.org/10.1016/B978-0-08-101011-2.00008-8
- Michiko Shigyo, Chihiro Tohda. Extracellular vimentin is a novel axonal growth facilitator for functional recovery in spinal cord-injured mice. Scientific Reports 2016, 6
(1)
https://doi.org/10.1038/srep28293
- Larry Yet. Olefin Ring‐Closing Metathesis. 2016, 1-1304. https://doi.org/10.1002/0471264180.or089.01
- Liang Feng, Yuehui Liu, Bo Hou, Zaifeng Yuan, Fu-Chao Yu, Tingbin Yan, Qi Qin, Ruigeng Ji, Ya-Min Li, Yuehai Shen, Zhi-Li Zuo. Hydrogen bonding-promoted efficient Ru-catalyzed ring-closing metathesis of demanding homoallyl 2-(hydroxymethyl)acrylates. Organic & Biomolecular Chemistry 2016, 14
(45)
, 10705-10713. https://doi.org/10.1039/C6OB02129H
- Jakub Švenda, Michael Sheremet, Lea Kremer, Lukáš Maier, Jonathan O. Bauer, Carsten Strohmann, Slava Ziegler, Kamal Kumar, Herbert Waldmann. Biology-Oriented Synthesis of a Withanolide-Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling. Angewandte Chemie 2015, 127
(19)
, 5688-5694. https://doi.org/10.1002/ange.201500112
- Jakub Švenda, Michael Sheremet, Lea Kremer, Lukáš Maier, Jonathan O. Bauer, Carsten Strohmann, Slava Ziegler, Kamal Kumar, Herbert Waldmann. Biology‐Oriented Synthesis of a Withanolide‐Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling. Angewandte Chemie International Edition 2015, 54
(19)
, 5596-5602. https://doi.org/10.1002/anie.201500112
- Michael Raymond, Shawn K. Collins. Dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene) Ruthenium(II). 2014, 1-4. https://doi.org/10.1002/047084289X.rn01758
- Bao-Le Zhang, Li-Xing Song, Ya-Fei Li, Yi-Lei Li, Ya-Zhuo Guo, En Zhang, Hong-Min Liu. Synthesis and biological evaluation of dehydroepiandrosterone-fused thiazole, imidazo[2,1-b]thiazole, pyridine steroidal analogues. Steroids 2014, 80 , 92-101. https://doi.org/10.1016/j.steroids.2013.12.003
- Bao-Le Zhang, En Zhang, Lu-Ping Pang, Li-Xing Song, Ya-Fei Li, Bin Yu, Hong-Min Liu. Design and synthesis of novel D-ring fused steroidal heterocycles. Steroids 2013, 78
(12-13)
, 1200-1208. https://doi.org/10.1016/j.steroids.2013.07.006
- Bin Yu, En Zhang, Xiao-Nan Sun, Jing-Li Ren, Yuan Fang, Bao-Le Zhang, De-Quan Yu, Hong-Min Liu. Facile synthesis of novel D-ring modified steroidal dienamides via rearrangement of 2H-pyrans. Steroids 2013, 78
(5)
, 494-499. https://doi.org/10.1016/j.steroids.2013.02.004
- Shuji Yamashita, Masafumi Himuro, Yujiro Hayashi, Masahiro Hirama. Remote C–H bond functionalization of androstane C-ring: C12-amination. Tetrahedron Letters 2013, 54
(10)
, 1307-1308. https://doi.org/10.1016/j.tetlet.2012.12.103
- Kiyoshi Teshigawara, Tomoharu Kuboyama, Michiko Shigyo, Aiko Nagata, Kenji Sugimoto, Yuji Matsuya, Chihiro Tohda. A novel compound, denosomin, ameliorates spinal cord injury via axonal growth associated with astrocyte‐secreted vimentin. British Journal of Pharmacology 2013, 168
(4)
, 903-919. https://doi.org/10.1111/j.1476-5381.2012.02211.x
- Yi-Zhen Yin, Chao Liu, Long-Qian Tang, Zhao-Peng Liu. Recoverable Pd/C catalyst mediated dehydrogenation of sterols and an improved synthesis of 1α-hydroxydehydroepiandrosterone. Steroids 2012, 77
(13)
, 1419-1422. https://doi.org/10.1016/j.steroids.2012.08.018
- Jonathan B. Johnston, Arti A. Singh, Anaelle A. Clary, Chiung-Kuan Chen, Patricia Y. Hayes, Sharon Chow, James J. De Voss, Paul R. Ortiz de Montellano. Substrate analog studies of the ω-regiospecificity of Mycobacterium tuberculosis cholesterol metabolizing cytochrome P450 enzymes CYP124A1, CYP125A1 and CYP142A1. Bioorganic & Medicinal Chemistry 2012, 20
(13)
, 4064-4081. https://doi.org/10.1016/j.bmc.2012.05.003
- Kenji Sugimoto, Kosuke Tamura, Naoki Ohta, Chihiro Tohda, Naoki Toyooka, Hideo Nemoto, Yuji Matsuya. Synthesis of dihydrofuran-fused perhydrophenanthrenes having a phenolic hydroxyl group as a novel anti-Alzheimer’s disease agent. Bioorganic & Medicinal Chemistry Letters 2012, 22
(1)
, 449-452. https://doi.org/10.1016/j.bmcl.2011.10.127
- Kenji Sugimoto, Yuta Kobayashi, Ayana Hori, Takashi Kondo, Naoki Toyooka, Hideo Nemoto, Yuji Matsuya. Syntheses of aza-analogues of macrosphelides via RCM strategy and their biological evaluation. Tetrahedron 2011, 67
(40)
, 7681-7685. https://doi.org/10.1016/j.tet.2011.08.014
- Laïla Kihel. DHEA and Alzheimer's Disease. 2011, 433-445. https://doi.org/10.1201/b11019-41
- Eri Joyashiki, Yuji Matsuya, Chihiro Tohda. Sominone Improves Memory Impairments and Increases Axonal Density in Alzheimer's Disease Model Mice, 5XFAD. International Journal of Neuroscience 2011, 121
(4)
, 181-190. https://doi.org/10.3109/00207454.2010.541571
- James W. Herndon. The chemistry of the carbon–transition metal double and triple bond: Annual survey covering the year 2009. Coordination Chemistry Reviews 2011, 255
(1-2)
, 3-100. https://doi.org/10.1016/j.ccr.2010.07.003
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