Total Synthesis of Anticancer Pacharin, Bauhiniastatin 4, and Bauhinoxepins C and D

Pattarapon Sang-aroon; Norasian Boosaman; Intouch Rakchaya; Wiradet Siri; Asamaporn Tieojaroenkit; Nutthawat Chuanopparat; Paiboon Ngernmeesri

doi:10.1055/a-2550-7239

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2550-7239

paper

Total Synthesis of Anticancer Pacharin, Bauhiniastatin 4, and Bauhinoxepins C and D

Pattarapon Sang-aroon‡

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

^bCenter of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Norasian Boosaman‡

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

^bCenter of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Intouch Rakchaya‡

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

^bCenter of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Wiradet Siri

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Asamaporn Tieojaroenkit

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Nutthawat Chuanopparat

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

^bCenter of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

,

Paiboon Ngernmeesri ∗

^aDepartment of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

^bCenter of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand

› Author Affiliations

Abstract

All articles of this category

Abstract

Reported herein is the total synthesis of anticancer pacharin, bauhiniastatin 4, and bauhinoxepins C and D. The synthetic strategy features a cascade reaction involving intermolecular nucleophilic aromatic substitution followed by intramolecular Knoevenagel condensation to form a dibenzo[b,f]oxepine scaffold of these compounds. Pacharin and bauhiniastatin 4 were synthesized in eight steps from 2-methylresorcinol with overall yields of 5.4% and 8.3%, respectively. Similarly, bauhinoxepins C and D were synthesized in seven steps with overall yields of 3.5% and 2.6%, respectively. This methodology offers an efficient route for accessing these natural products with implications for medicinal and synthetic chemistry.

Key words

natural product synthesis - cascade reaction - dibenzo[b,f]oxepines - anticancer agents - nucleophilic aromatic substitution - Knoevenagel condensation

Full Text

References

References
1 Anjaneyulu AS. R, Raghava Reddy AV, Reddy DS. K, Ward RS, Adhikesavalu D, Stanley Cameron T. Tetrahedron 1984; 40: 4245
2 Pettit GR, Numata A, Iwamoto C, Usami Y, Yamada T, Ohishi H, Cragg GM. J. Nat. Prod. 2006; 69: 323
3 da Silva HC, Pinto F. dC. L, de Sousa AF, Pessoa OD. L, Trevisan MT. S, Santiago GM. P. Nat. Prod. Res. 2021; 35: 5277
4 Comber MF, Sargent MV. J. Chem. Soc., Perkin Trans. 1 1990; 1371
5 Boonphong S, Puangsombat P, Baramee A, Mahidol C, Ruchirawat S, Kittakoop P. J. Nat. Prod. 2007; 70: 795

6a Heel RC, Brogden RN, Speight TM, Avery GS. Drugs 1978; 15: 198
6b Chakrabarti A, Bagnall A.-M, Chue P, Fenton M, Palanisamy V, Wong W, Xia J. Cochrane Database of Systematic Reviews 2007; CD001943

7a Greenblatt EN, Lippa AS, Osterberg AC. Arch. Int. Pharmacodyn. Ther. 1978; 233: 107
7b Kinney JL, Evans RL. Jr. Clin. Pharm. 1982; 1: 417

8 Krawczyk H. Int. J. Mol. Sci. 2023; 24: 10266
9 Olivera R, Sanmartin R, Churruca F, Domínguez E. Org. Prep. Proced. Int. 2004; 36: 297

10a Nagai Y, Irie A, Nakamura H, Hino K, Uno H, Nishimura H. J. Med. Chem. 1982; 25: 1065
10b Harris TW, Smith HE, Mobley PL, Manier DH, Sulser F. J. Med. Chem. 1982; 25: 855
10c Bharath Y, Thirupathi B, Ranjit G, Mohapatra DK. Asian J. Org. Chem. 2013; 2: 848
10d Wang Y, Chen Y, He Q, Xie Y, Yang C. Helv. Chim. Acta 2013; 96: 296

11 Matsuda T, Sato S. J. Org. Chem. 2013; 78: 3329
12 Moreno DR. R, Giorgi G, Salas CO, Tapia RA. Molecules 2013; 18: 14797
13 Cong Z, Miki T, Urakawa O, Nishino H. J. Org. Chem. 2009; 74: 3978

14a Arnold LA, Luo W, Guy RK. Org. Lett. 2004; 6: 3005
14b Jepsen TH, Larsen M, Jørgensen M, Nielsen MB. Synlett 2012; 23: 418

15 Storz T, Vangrevelinghe E, Dittmar P. Synthesis 2005; 2562

16a Ong HH, Profitt JA, Anderson VB, Spaulding TC, Wilker JC, Geyer HM, Kruse H. J. Med. Chem. 1980; 23: 494
16b Paduraru MP, Wilson PD. Org. Lett. 2003; 5: 4911

17a Chernysheva NB, Samet AV, Marshalkin VN, Polukeev VA, Semenov VV. Mendeleev Commun. 2001; 11: 109
17b Samet AV, Marshalkin VN, Lyssenko KA, Semenov VV. Russ. Chem. Bull. 2009; 58: 347
17c Krawczyk H, Wrzesiński M, Mielecki D, Szczeciński P, Grzesiuk E. Tetrahedron 2016; 72: 3877

18 Choi YL, Lim HS, Lim HJ, Heo J.-N. Org. Lett. 2012; 14: 5102
19 Taweesak P, Thongaram P, Kraikruan P, Thanetchaiyakup A, Chuanopparat N, Hsieh H.-P, Uang B.-J, Ngernmeesri P. J. Org. Chem. 2021; 86: 1955
20 Castillo-Vallés M, Cano M, Bermejo-Sanz A, Gimeno N, Ros MB. J. Mater. Chem. C 2020; 8: 1998

21a Lehtio L, Maksimainen M, Murthy SN, Tabarrini O, Nizi MG, Massari S. WO2023144450, 2023
21b Thongaram P, Borwornpinyo S, Kanjanasirirat P, Jearawuttanakul K, Kongsema M, Chuanopparat N, Ngernmeesri P. Tetrahedron 2020; 76: 131473

Supplementary Material

Supporting Information