ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Selective mono-deprotection strategy for efficient synthesis of Trabectedin, Lurbinectedin key intermediate

Chandrasekhar Byravakunta, Ramesh Kola, Nareshkumar Reddy Kondampally, Subba Narasimhulu Porala, and Sathishkumar Rajkumar

Department of Chemistry, Bharatiya Engineering Science and Technology Innovation University, Gownivaripalli, Gorantla, India

E-mail: ramscbit@gmail.com

Received: 22 December 2025  Accepted: 20 March 2026

Abstract:

A novel synthetic approach to the key pentacyclic phenol intermediate 1, common to Trabectedin 3 and Lurbinectedin 4, is described. This manuscript presents a convergent synthetic strategy involving aryl di-triflates 13 and 14 as efficient alternatives to the previously reported aryl mono-triflate 6. The study focuses on the selective mono-deprotection of bis(triflate) 14 to a mono-triflate 8, followed by hydroxyl group protection to obtain aryl O-MOM mono-triflate 9. Optimal conditions were identified and applied for the efficient synthesis of the key intermediate 9. Further synthetic advancement involved a Kumada coupling reaction, facilitating the C-methylation of 9 to the corresponding alkane 15. This strategy ultimately delivers the key pentacyclic phenol 1 with controlled desmethyl impurity 12, a significant improvement in overall yield (68% vs. 51%), use of cost-effective reagents, and adherence to green chemistry principles. The method demonstrates operational simplicity and scalability, suitable for multigram-scale synthesis.

Graphical abstract

Keywords: Aryl di-triflate; Aryl mono trifilate; Kumada coupling reaction; Des-methyl impurity; Green chemistry

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04833-2

Chemical Papers 80 (7) 7517–7523 (2026)