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Synthesis 2025; 57(23): 3565-3578
DOI: 10.1055/a-2688-5484
DOI: 10.1055/a-2688-5484
Short Review
Published as part of the Special Topic C–S Bond Forming and Cleaving Reactions
Recent Advances in the Total Synthesis of Sulfur-containing Natural Products
Authors
This work was supported by the 2024 Research Fund of the University of Seoul for Sanghyeon Lee. Also this study was supported by 2022 Research Grant from Kangwon National University for Wonchul Lee.
Supported by: Kangwon National University 2022 Research Grant
Abstract
Sulfur imparts distinctive reactivity, conformational bias, and redox versatility to natural products, giving rise to potent antibacterial, antiviral, anticancer, and enzyme-inhibitory activities. Over the past five years, highly regio- and stereoselective C–S bond-forming strategies have enabled concise access to increasingly complex sulfur frameworks. This review surveys representative total syntheses reported from March 2020 to January 2024, grouped by sulfur functionality—thioethers, disulfides, sulfoxides, thioacetals, thiazoles, thiazolines, and isothiazolinones—and shows how these advances shorten step counts, facilitate late-stage diversification, and provide a foundation for rapid structure–activity relationship studies of sulfur-rich scaffolds poised for therapeutic development.
Keywords
Total synthesis - Sulfur-containing natural products - Thioether - Disulfide - Oxysulfur - Thiazole - ThiazolinePublication History
Received: 10 July 2025
Accepted after revision: 21 August 2025
Accepted Manuscript online:
21 August 2025
Article published online:
08 October 2025
© 2025. Thieme. All rights reserved.
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References
- 1 Hai Y, Wei M, Wang C, Gu Y, Shao C. Mar Life Sci Technol 2021; 3: 488
- 2 Liu Z, Li M, Wang S, Huang H, Zhang W. Mar Drugs 2022; 20: 765
- 3 Guo F, Zhang Q, Gu Y, Shao C. Curr Opin Chem Biol 2023; 75: 102330
- 4 Wang N, Saidhareddy P, Jiang X. Nat Prod Rep 2013; 37: 246
- 5a Pan C, Kuranaga T, Kakeya H. Org Biomol Chem 2020; 18: 8366
- 5b Xiao Y, Jiang Y, Xu C. et al. Org Chem Front 2022; 9: 3998
- 6 He C, Chu H, Stratton TP. et al. J Am Chem Soc 2020; 142: 13683
- 7 Koning NR, Sundin AP, Strand D. J Am Chem Soc 2021; 143: 21218
- 8 Zhang J, Suzuki K, Ohmori K. Org Lett 2023; 25: 9036
- 9a Akasapu S, Hinds AB, Powell WC, Walczak MA. Chem Sci 1971; 2019: 10
- 9b Christy MP, Johnson T, Mcnerlin CD. et al. Org Lett 2020; 22: 2365
- 10 Bauer K, Kazmaier U. Angew Chem Int Ed 2023; 62: e202305445
- 11 Kurisawa N, Iwasaki A, Teranuma K. et al. J Am Chem Soc 2022; 144: 11019
- 12 Jiang Y, Liu X, Li W, Jiao X, Xie P. J Org Chem 2023; 88: 3981
- 13 Yahata K, Fürstner A. Angew Chem Int Ed 2024; 63: e202319070
- 14 Shimomura M, Ide K, Sakata J, Tokuyama H. J Am Chem Soc 2023; 145: 18233
- 15 Yu H, Sercel ZP, Rezgui SP, Farhi J, Virgil SC, Stoltz BM. J Am Chem Soc 2023; 145: 25533-25537
- 16 Kojima K, Yakushiji F, Katsuyama A, Ichikawa S. Org Lett 2020; 22: 4217
- 17 Thesmar P, Baudoin O. J Am Chem Soc 2019; 141: 15779
- 18a Ferko B, Zeman M, Formica M. et al. J Org Chem 2019; 84: 7159
- 18b Malatinský T, Valachová D, Pinčeková L. et al. Org Biomol Chem 2022; 20: 7821
- 18c Schriefer MG, Schrey H, Zeng H, Stadler M, Schobert R. Org Biomol Chem 2021; 19: 4743
- 18d Schmidt F, Ammanath AV, Götz F, Maier ME. Eur J Org Chem 2023; 26: e202300615
- 19 Yamazaki K, Okuda Y, Takaya A, Nemoto T. Org Lett 2024; 26: 670
- 20 Pan C, Kuranaga T, Liu C, Lu S, Shinzato N, Kakeya H. Org Lett 2020; 22: 3014
- 21 Oppolzer W. Pure Appl Chem 1990; 62: 1241
- 22 Heravi MM, Zadsirjan V. Tetrahedron Asymmetry 2014; 25: 1061
- 23 Hellmers E. Acta Agric Scand 1955; 5: 185
- 24 Mitchell RE, Durbin RD. Physiol Plant Pathol 1981; 18: 157
- 25 Mathews DE, Durbin RD. J Biol Chem 1990; 265: 493
- 26 Mitchell RE, Hart PA. Phytochemistry 1983; 22: 1425
- 27 Mitchell RE, Coddington JM, Young H. Tetrahedron Lett 1989; 30: 501
- 28 Aliev AE, Karu K, Mitchell RE, Porter MJ. Org Biomol Chem 2015; 14: 238
- 29 Yamada H, Adachi M, Nishikawa T. Chem Commun 2013; 49: 11221
- 30 Dent BR, Furneaux RH, Gainsford GJ, Lynch GP. Tetrahedron 1999; 55: 6977
- 31 Ioannou M, Porter MJ, Saez F. Chem Commun 2002; 346
- 32 Plet JRH, Porter MJ. Chem Commun 2006; 1197
- 33 Mortimer AJP, Aliev AE, Tocher DA, Porter MJ. Org Lett 2008; 10: 5477
- 34 Mortimer AJP, Plet JRH, Obasanjo OA, Kaltsoyannis N, Porter MJ. Org Biomol Chem 2012; 10: 8616
- 35 Ferrier RJ, Vethaviyasar N. J Chem Soc D 1970; 1385-1387
- 36 Mingat G, Clayden J. Synthesis 2012; 44: 2723
- 37 Knouse KW, deGruyter JN, Schmidt MA. et al. Science 2018; 361: 1234
- 38 Park HB, Kwon HC, Lee C, Yang HO. J Nat Prod 2009; 72: 248
- 39 Park HB, Kim Y, Park J, Yang HO, Lee KR, Kwon HC. J Nat Prod 2011; 74: 2309
- 40 Kim Y, Park HB, Yoo J, Kwon HC, Kim J, Yang HO. Biol Pharm Bull 2014; 37: 378
- 41 Maguire OR, Taylor B, Higgins EM. et al. Chem Sci 2020; 11: 7722
- 42 Hara M, Takahashi I, Yoshida M. et al. J Antibiot 1989; 42: 333
- 43 Hirayama N, Matsuzawa ES. Chem Lett 1957; 1993: 22
- 44 Bassett S, Urrabaz R, Sun D. Anti-Cancer Drugs 2004; 15: 689
- 45 Keerthi K, Rajapakse A, Sun D, Gates KS. Bioorg Med Chem 2013; 21: 235
- 46 Chatterji T, Kizil M, Keerthi K, Chowdhury G, Pospísil T, Gates KS. J Am Chem Soc 2003; 125: 4996
- 47 Pan G, Xu Z, Guo Z. et al. Proc Natl Acad Sci U S A 2017; 114: E11131
- 48 Becerril A, Pérez-Victoria I, Ye S. et al. ACS Chem Biol 2020; 15: 1541-1553
- 49 Kanda Y, Fukuyama T. J Am Chem Soc 1993; 115: 8451-8452
- 50 Kanda Y, Saito H, Fukuyama T. Tetrahedron Lett 1992; 33: 5701
- 51 Fürstner A. Angew Chem Int Ed 2013; 52: 2794
- 52 Fürstner A. J Am Chem Soc 2021; 143: 15538
- 53 Schaubach S, Gebauer K, Ungeheuer F. et al. Chem Eur J 2016; 22: 8494
- 54 Hantzsch A, Weber JH. Ber Dtsch Chem Ges 1887; 20: 3118
- 55 Schmidt U, Gleich P, Griesser H, Utz R. Synthesis 1986; 1986: 992
- 56 Zou Y, Wang X, Sims J. et al. J Am Chem Soc 2019; 141: 4338
- 57 Perry NB, Blunt JW, Munro MHG. Tetrahedron 1988; 44: 1727
- 58 Lee O, Law K, Ho C, Yang D. J Org Chem 2008; 73: 8829
- 59 Rousseaux S, García-Fortanet J, Del Aguila Sanchez MA, Buchwald SL. J Am Chem Soc 2011; 133: 9282
- 60 Le DN, Johnson HC, Lam Y, Sun C, Cheng L, Belyk KM. Org Lett 2024; 26: 4059
- 61 Bartels F, Weber M, Christmann M. Org Lett 2020; 22: 552
- 62 Chesnokov GA, Gademann K. J Am Chem Soc 2021; 143 (35) 14083
- 63 Ebihara A, Iwasaki A, Miura Y, Jeelani G, Nozaki T, Suenaga K. J Org Chem 2021; 86: 11763
- 64 Argoudelis AD. Agents Chemother 1962; 780
- 65 Ubukata M, Morita T, Uramoto M, Osada H. J Antibiot 1996; 49: 65
- 66 Ubukata M, Morita T, Kakeya H, Kobinata K, Kudo T, Osada H. J Antibiot 1996; 49: 1096
- 67 Ottenheijm HCJ, Liskamp RMJ, Van Nispen SPJM, Boots HA, Tijhuis MW. J Org Chem 1981; 46: 3273
- 68 Nakajima N, Enomoto T, Watanabe T, Matsuura N, Ubukata M. Biosci Biotechnol Biochem 2003; 67: 2556
- 69 Li S, Cheng X, Zhou Y, Xi Z. ChemBioChem 2011; 12: 2801-2806
- 70 Schwan AL, Verdu MJ, Singh SP, O’Donnell JS, Ahmadi AN. J Org Chem 2009; 74: 6851
- 71 Newhouse TR, Li X, Blewett MM, Whitehead CMC, Corey EJ. J Am Chem Soc 2012; 134: 17354
- 72 Torres-Hernandez AX, Desman P, Nguyen T. et al. Chem – Eur J Dermatol 2023; 30: e202303316
- 73 Miyamoto Y, Iwasaki A, Fujimura H. et al. J Org Chem 2023; 88: 3208
- 74 Nitelet A, Gérard P, Bouche J, Evano G. Org Lett 2019; 21: 4318
- 75 Morrison RJ, Van Der Mei FW, Romiti F, Hoveyda AH. J Am Chem Soc 2019; 142: 436
- 76a Long B, Tao C, Li Y, Zeng X, Cao M, Wu Z. Org Biomol Chem 2020; 18: 5349
- 76b Vishwanatha TM, Giepmans B, Goda SK, Dömling A. Org Lett 2020; 22: 5396
- 77 Wu F, Yu J, Meng J, Guo Y, Ye T. Molecules 2021; 26: 4224
- 78 Shingare RD, Aniebok V, Lee H, Macmillan JB. Org Lett 2020; 22: 1516
- 79 Taylor KS, Zhang C, Glukhov E, Gerwick WH, Suyama TL. J Nat Prod 2021; 84: 865
- 80 Andler O, Kazmaier U. Org Biomol Chem 2021; 19: 4866
- 81 Su TL. Br J Exp Pathol 1948; 29: 473
- 82 Fuller AT. Nature 1955; 175: 722
- 83 Lefranc D, Ciufolini MA. Angew Chem Int Ed 2009; 48: 4198
- 84 Chan DCK, Burrows LL. J Antibiot 2021; 74: 161
- 85 Haack PA, Harmrolfs K, Bader CD. et al. Angew Chem Int Ed 2022; 61: e202212946
- 86 Aguilar E, Meyers AI. Tetrahedron Lett 1994; 35: 2473
- 87 You S, Razavi H, Kelly JW. Angew Chem Int Ed 2003; 42: 83
- 88 Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M. Bull Chem Soc Jpn 1989; 1979: 52
- 89a Rasmussen U, Brøogger Christensen S, Sandberg F. Acta Pharm Suec 1978; 15: 133
- 89b Teruya T, Sasaki H, Kitamura K, Nakayama T, Suenaga K. Org Lett 2009; 11: 2421
- 89c Morita M, Ohno O, Teruya T, Yamori T, Inuzuka T, Suenaga K. Tetrahedron 2012; 68: 5984
- 90a Owusu-Ansah E, Durow AC, Harding JR, Jordan AC, O'Connell SJ, Willis CL. Org Biomol Chem 2010; 9: 265
- 90b Lalithamba HS, Uma K, Gowthami TS, Nagendra G. Org Prep Proced Int 2020; 52: 181
- 91 Liang L, Haltli B, Marchbank DH. et al. J Org Chem 2020; 85: 6450
- 92 Burckhardt T, Harms K, Koert U. Org Lett 2012; 14: 4674
- 93 Corbaz R, Ettlinger L, Gäumann E. et al. Helv Chim Acta 1957; 40: 199
- 94 Kong D, Park EJ, Stephen AG. et al. Cancer Res 2005; 65: 9047
- 95a Ponnurangam S, Dandawate PR, Dhar A. et al. Oncotarget 2015; 7: 3217
- 95b Wang Y, Liu Y, Tang F. et al. Blood 2014; 124: 1127
- 96 Kojima K, Konishi H, Momosaki K. et al. Sci Rep 2024; 14: 7628
- 97 Liu J, Ekberg R, Koning NR, Strand D. Angew Chem Int Ed 2024; 63: e202412397
- 98 Zhang Y, Saha S, Esser YCC, Ting CP. J Am Chem Soc 2024; 146: 17629
- 99 Mo Z, Wang X, Liu L, Tian S, Tang Y. Org Lett 2025; 27: 6001
- 100 Zhou T, Fan Y, Zhang J, Wang B. ACS Bio Med Chem Au 2024; 5: 16
- 101 Dunbar KL, Scharf DH, Litomska A, Hertweck C. Chem Rev 2017; 117: 5521
- 102 Wu Z, Pratt DA. Nat Rev Chem 2023; 7: 573
- 103 Zhu J, Yang W, Wang X, Wu L. Adv Synth Catal 2018; 360: 386
- 104 Guo W, Tao K, Tan W, Zhao M, Zheng L, Fan X. Org Chem Front 2019; 6: 2048
- 105 Mahmudov KT, Kopylovich MN, da Silva MFCG, Pombeiro AJ. Dalton Trans 2017; 46: 10121