The Cargill-Type Rearrangement in Natural Product Synthesis

Wen Xun; Deyun Ma; Rimeng Chen; Shaobin Su; Bo Xu

doi:10.1055/a-2640-7480

Synthesis, Table of Contents

Synthesis 2025; 57(19): 2765-2782
DOI: 10.1055/a-2640-7480

Short Review

The Cargill-Type Rearrangement in Natural Product Synthesis

Authors

Wen Xun

¹School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, China
Deyun Ma

¹School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, China
Rimeng Chen

³Zhanjiang Institute for Food and Drug Control, Zhanjiang, China
Shaobin Su

⁴Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Bo Xu

²State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China

Abstract

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Abstract

Natural products are a prolific source of drug leads due to their unique architectures and potent bioactivity. However, their structural complexity often presents formidable challenges for total synthesis. Skeletal editing has recently emerged as a powerful strategy to streamline synthetic routes by selectively reorganizing molecular frameworks. In this context, the Cargill-type rearrangement offers a unique yet underutilized approach to skeletal editing via carbonyl migration. Despite its value, this transformation has not been systematically reviewed. Here, we provide the first focused summary of Cargill-type rearrangements in natural product synthesis, highlighting mechanistic insights and key examples to illustrate their synthetic potential.

Keywords

Cargill-type rearrangement - Skeletal editing - Strain release - Total synthesis - Natural products

Full Text

References

References

1a Nicolaou KC, Vourloumis D, Winssinger N, Baran PS. Angew Chem, Int Ed 2000; 39: 44-122
1b Nicolaou KC, Rigol S, Yu R. CCS Chem 2019; 1: 3-37
1c Nicolaou KC, Rigol S. Nat Prod Rep 2020; 37: 1404-1435
1d Reisman SE, Maimone TJ. Acc Chem Res 2021; 54: 1815-1816
1e Shenvi RA. Science 2024; 10: 519-528

2a Harvey AL, Edrada-Ebel R, Quinn RJ. Nat Rev Drug Discovery 2015; 14: 111-129
2b Newman DJ, Cragg GM. J Nat Prod 2020; 83: 770-803
2c Wilson RM, Danishefsky SJ. J Org Chem 2006; 7: 8329-8351
2d Wang S, Dong G, Sheng C. Chem Rev 2019; 119: 4180-4220
2e Heinzke AL, Pahl A, Zdrazil B. et al. J Med Chem 2024; 67: 11226-11241

3a Newhouse T, Baran PS, Hoffmann RW. Chem Soc Rev 2009; 38: 3010-3021
3b Gaich T, Baran PS. J Org Chem 2010; 75: 4657-4673
3c Schwan J, Christmann M. Chem Soc Rev 2018; 47: 7985-7995
3d Peters DS, Pitts CR, McClymont KS, Stratton TP, Bi C, Baran PS. Acc Chem Res 2021; 54: 605-617
3e Gao Y, Ma D. Acc Chem Res 2021; 54: 569-582
3f Hoffmann RW. Chem Soc Rev 2025; 54: 3242-3246

4a Kuttruff CA, Eastgate MD, Baran PS. Nat Prod Rep 2014; 31: 419-432
4b Fay N, Kouklovsky C, de la Torre A. ACS Org Inorg Au 2023; 3: 350-363

5a Kim SF, Amber C, Bartholomew GL, Sarpong R. Acc Chem Res 2025; 58: 1786-1800
5b Al-Ahmad R, Dai M. Acc Chem Res 2025; 58: 1392-1406
5c Yuan T, Shi L. Org Chem Front 2024; 11: 7318-7332
5d Ma C, Lindsley CW, Chang J, Yu B. J Med Chem 2024; 67: 11459-11466
5e Li E-Q, Lindsley CW, Chang J, Yu B. J Med Chem 2024; 67: 13509-13511
5f Levin MD. Synlett 2023; 35: 1471-1474
5g Jurczyk J, Woo J, Kim SF, Dherange BD, Sarpong R, Levin MD. Nat Synth 2022; 1: 352-364
5h Hui C, Wang Z, Wang S, Xu C. Org Chem Front 2022; 9: 1451-1457

6a Cargill RL, Crawford JW. Tetrahedron Lett 1967; 8: 169-171
6b Cargill RL, Crawford JW. J Org Chem 1970; 35: 356-359
6c Peet NP, Cargill RL. J Org Chem 1973; 38: 4281-4285
6d Peet NP, Cargill RL, Bushey DF. J Org Chem 1973; 38: 1218-1221
6e Cargill RL, Jackson TE, Peet NP, Pond DM. Acc Chem Res 1974; 7: 106-113
6f Cargill RL, Bushey DF, Dalton JR, Prasad RS, Dyer RD, Bordner J. J Org Chem 1981; 46: 3389-3399

7a Song Z-L, Fan C-A, Tu Y-Q. Chem Rev 2011; 111: 7523-7556
7b Zhang X-M, Tu Y-Q, Zhang F-M, Chen Z-H, Wang S-H. Chem Soc Rev 2017; 46: 2272-2305
7c Delayre B, Wang Q, Zhu J. ACS Cent Sci 2021; 7: 559-569
7d Zhang X-M, Li B-S, Wang S-H, Zhang K, Zhang F-M, Tu Y-Q. Chem Sci 2021; 12: 9262-9274
7e Chen J, Li J, Long X, Shen H, Deng J. Chin J Org Chem 2025; 45: 896-912

8 Brägger Y, Green O, Bhawal BN, Morandi B. J Am Chem Soc 2023; 145: 19496-19502
9 Wu Z, Xu X, Wang J, Dong G. Science 2021; 374: 734-740
10 Duc DKM, Fetizon M, Lazare S. J Chem Soc, Chem Commun 1975; 282-282
11 Yanagiya M, Kaneko K, Kaji T, Matsumoto T. Tetrahedron Lett 1979; 20: 1761-1764

12a Pirrung MC. J Am Chem Soc 1979; 101: 7130-7131
12b Pirrung MC. J Am Chem Soc 1981; 103: 82-87

13a Smith III AB, Jerris PJ. J Am Chem Soc 1981; 103: 194-195
13b Smith III AB, Jerris PJ. J Org Chem 1982; 47: 1845-1855

14 White JD. Synthesis 1998; S1: 619-626
15 Xu B, Zhang Z, Tantillo DJ, Dai M. J Am Chem Soc 2024; 146: 21250-21256

16a Meinwald J, Labana SS, Chadha MS. J Am Chem Soc 1963; 85: 582-585
16b He J, Ling J, Chiu P. Chem Rev 2014; 114: 8037-8128
16c Mamedova VL, Khikmatova G n. Chem Heterocycl Compd 2017; 53: 976-978
16d Xu C, Xu J. Chem Heterocycl Compd 2021; 57: 731-733
16e Meninno S, Lattanzi A. ACS Org Inorg Au 2022; 2: 289-305
16f Zhang Y, Hu B, Chen Y, Wang Z. Chem Eur J 2024; 30: e202402469

17a Reetz MT. Angew Chem, Int Ed 1972; 11: 129-130
17b Reetz MT. Angew Chem, Int Ed 1972; 11: 130-131
17c Fernández I, Cossío FP, Sierra MA. Chem Rev 2009; 109: 6687-6711
17d Gutierrez O, Tantillo DJ. J Org Chem 2012; 77: 8845-8850
17e Leverett CA, Purohit VC, Johnson AG, Davis RL, Tantillo DJ, Romo D. J Am Chem Soc 2012; 134: 13348-13356
17f Hugelshofer CL, Magauer T. J Am Chem Soc 2016; 138: 6420-6423
17g Hugelshofer CL, Magauer T. Nat Prod Rep 2017; 34: 228-234
17h Guo Z, Bao R, Li Y, Li Y, Zhang J, Tang Y. Angew Chem, Int Ed 2021; 60: 14545-14553
17i Reetz MT. Isr J Chem 2023; 63: e202200122
17j Gong J, Wang Q, Zhu J. J Am Chem Soc 2025; 147: 2077-2085
17k Li Y, Zhang J, Chen Y, Pang J, Chen Y, Tang Y. Angew Chem, Int Ed 2025; 64: e202414985

18 Zhang Z, Qian X, Gu Y, Gui J. Nat Prod Rep 2024; 41: 251-272
19 Kakiuchi K, Ue M, Tsukahara H. et al. J Am Chem Soc 1989; 111: 3707-3712
20 Narasaka K, Shimadzu H, Hayashi Y. Chem Lett 1993; 22: 621-624
21 Fedorov SN, Radchenko OS, Shubina LK. et al. J Am Chem Soc 2001; 123: 504-505
22 Day JJ, McFadden RM, Virgil SC, Kolding H, Alleva JL, Stoltz BM. Angew Chem, Int Ed 2011; 50: 6814-6818
23 Wang X-N, Krenske EH, Johnston RC, Houk KN, Hsung RP. J Am Chem Soc 2015; 137: 5596-5601
24 Bormann CT, Fadaei-Tirani F, Scopelliti R, Severin K. Org Biomol Chem 2021; 19: 8113-8117
25 Ogura K, Yamashita M, Onozuka J, Tushihashi G-i. Tetrahedron Lett 1983; 24: 79-82
26 Fujiwara T, Tomaru J-i, Suda A, Takeda T. Tetrahedron Lett 1992; 33: 2583-2586
27 Hart H, Love GM. J Am Chem Soc 1971; 93: 6264-6266

28a Nair V, Anilkumar G, Eigendorf GK, Williard PG. Tetrahedron Lett 1996; 37: 8271-8272
28b Nair V, Maliakal D, Treesa PM. et al. Tetrahedron 2000; 56: 3735-3741

29 Song L, Zhu G, Liu Y, Liu B, Qin S. J Am Chem Soc 2015; 137: 13706-13714
30 Laing M, Sommerville P, Hanouskova D. et al. J Chem Soc, Chem Commun 1972; 196-198

31a Selvakumar N, Rao GSRS. J Chem Soc, Chem Commun 1994; 1303-1304
31b Selvakumar N, Janaki SN, Pramod K, Rao GSRS. J Chem Soc Perkin Trans 1995; 1: 839-846

32 Danheiser RL, Fink DM. Tetrahedron Lett 1985; 26: 2513-2516
33 Barclay LRC, Young RH, Adams KL, Foote HM. Can J Chem 1973; 51: 1598-1609
34 Jee DW, Lee H-YA. J Org Chem 2021; 10: 820-826
35 Trost BM, McDougal PG, Haller KJ. J Am Chem Soc 1984; 106: 383-395