Biosynthetic Approach toward Drimentines and Indotertines: Study of Acid-promoted Transformation of 3a-Prenylpyrroloindolines

Abstract

For developing a biomimetic synthetic route for bioactive hybrid isoprenoid indotertine and drimentine derivatives, we investigated acid-mediated cyclization/isomerization reactions of 3a-prenyl and 3a-geranyl pyrroloindolines. In the case of the 3a-prenyl derivatives, we discovered a skeletal rearrangement reaction initiated by the opening of pyrrolidine rings. For 3a-geranyl derivatives, we successfully constructed a tetracyclic framework corresponding to the substructure of the indotertines.

Keywords

Drimentines - Indotertines - Pyrroloindoline - Prenyl isomerization - Prenyl migration - Polyene cyclization

Publication History

Received: 30 August 2025

Accepted after revision: 01 October 2025

Accepted Manuscript online:
01 October 2025

Article published online:
27 October 2025

• References

• 1 Tietze LF, Bell HP, Chandrasekhar S. Angew Chem Int Ed 2003; 42: 3996-4028
• 2a Matsuda Y, Abe I. Nat Prod Rep 2016; 33: 26-53
• 2b Gozari M, Alborz M, El-Seedi HR, Jassbi AR. Eur J Med Chem 2021; 210: 112957
• 2c Gallagher KA, Fenical W, Jensen PR. Curr Opin Biotechnol 2010; 21: 794-800
• 3a Li F, Renata H. J Am Chem Soc 2021; 143: 18280-18286
• 3b Li H, Sun Y, Zhang O, Zhu Y, Li S-M, Li A. Org Lett 2015; 17: 306-309
• 4 Jakubczyk D, Cheng JZ, O'Connor SE. Nat Prod Rep 2014; 31: 1328-1338
• 5 Lacey E, Power M, Wu Z, Rickards RW. Patent Int. Appl. WO9809968 A1, 19980312 1998
• 6 Che Q, Zhu T, Qi X. et al. Org Lett 2012; 14: 3438-3441
• 7 Che Q, Zhu T, Keyzers RA. et al. J Nat Prod 2013; 76: 759-763
• 8 Che Q, Li J, Li D, Gu Q, Zhu T. J Antibiot 2016; 69: 467-469
• 9a Yao T, Liu J, Liu Z. et al. Nat Commun 2018; 9: 4091
• 9b Marcos IS, Moro RF, Costales I, Basabe P, Díez D. Nat Prod Rep 2013; 30: 1509-1526
• 10 Sun Y, Li R, Zhang W, Li A. Angew Chem Int Ed 2013; 52: 9201-9204

Selected references for polyene cyclization:
• 11a Snyder SA, Levinson AM. Comprehensive Organic Synthesis II. Oxford: Elsevier; 2014: 268
• 11b Sutherland JK. Compr Org Synth 1991; II [phone]
• 11c Yoder RA, Johnston JN. Chem Rev 2005; 105: 4730-4756
• 11d Ungarean CN, Southgate EH, Sarlah D. Org Biomol Chem 2016; 14: 5454-5467
• 11e Barrett AGM, Ma T-K, Mies T. Synthesis 2019; 51: 67-82
• 11f Ma T-K, Parsons PJ, Barrett AGM. J Org Chem 2019; 84: 4961-4970
• 11g Sun Y, Meng Z, Chen P. et al. Org Chem Front 2016; 3: 368-374
• 11h Trotta AH. Org Lett 2015; 17: 3358-3361
• 12a Ishihara K, Nakamura S, Yamamoto H. J Am Chem Soc 1999; 121: 4906-4907
• 12b Nakamura S, Ishihara K, Yamamoto H. J Am Chem Soc 2000; 122: 8131-8140
• 12c Ishihara K, Ishibashi H, Yamamoto H. J Am Chem Soc 2001; 123: 1505-1506
• 12d Ishihara K, Ishibashi H, Yamamoto H. J Am Chem Soc 2002; 124: 3647-3655
• 12e Ishibashi H, Ishihara K, Yamamoto H. J Am Chem Soc 2004; 126: 11122-11123
• 13 Sakakura A, Sakuma M, Ishihara K. Org Lett 2011; 13: 3130-3133
• 14a Luo N, Turberg M, Leutzsch M. et al. Nature 2024; 632: 795-801
• 14b Tsuji N, Kennemur JL, Buyck T. et al. Science 2018; 359: 1501-1505
• 15a Tan GH, Zhu X, Ganesan A. Org Lett 2003; 5: 1801-1803
• 15b Kimura M, Futamata M, Mukai R, Tamaru Y. J Am Chem Soc 2005; 127: 4592-4593
• 15c Trost BM, Quancard J. J Am Chem Soc 2006; 128: 6314-6315
• 15d Zhu Y, Rawal VH. J Am Chem Soc 2012; 134: 111-114
• 15e Liu Y, Du H. Org Lett 2013; 15: 740-743
• 15f Tu H-F, Zhang X, Zheng C, Zhu M, You S-L. Nat Catal 2018; 1: 601-608
• 15g Zhang H-J, Zhang H-J, Gu Q, You S-L. Org Lett 2019; 21: 9420-9424
• 16a Caballero E, Avendaño C, Menéndez JC. J Org Chem 2003; 68: 6944-6951
• 16b Cardoso ASP, Marques MMB, Srinivasan N, Prabhakar S, Lobo AM, Rzepa HS. Org Biomol Chem 2006; 4: 3966-3972
• 16c Cardoso AS, Lobo AM, Prabhakar S. Tetrahedron Lett 2000; 41: 3611-3613
• 17 Marion N, Navarro O, Mei J, Stevens ED, Scott NM, Nolan SP. J Am Chem Soc 2006; 128: 4101-4111
• 18 Mukherjee S, List B. J Am Chem Soc 2007; 129: 11336-11337
• 19 Ghosh S, Chaudhuri S, Bisai A. Org Lett 2015; 17: 1373-1376