Stereoselective total synthesis of (3 Z)- and (3 E)-elatenynes

Soo Yeon Kwak; Iljin Shin; Hongjun Jang; Youngjik Park; Seongju Lim; Dongjoo Lee; Hyoungsu Kim; Deukjoon Kim

doi:10.1039/d3ra07741a

Stereoselective total synthesis of (3 Z)- and (3 E)-elatenynes

RSC Adv. 2023 Dec 11;13(51):35920-35925. doi: 10.1039/d3ra07741a. eCollection 2023 Dec 8.

Authors

Soo Yeon Kwak¹, Iljin Shin¹, Hongjun Jang¹, Youngjik Park¹, Seongju Lim¹, Dongjoo Lee¹, Hyoungsu Kim¹, Deukjoon Kim²

Affiliations

¹ College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University Suwon 16499 Korea hkimajou@ajou.ac.kr.
² College of Pharmacy, Seoul National University Seoul 08826 Korea.

Abstract

We describe here the highly stereoselective total synthesis of the Laurencia C₁₅ acetogenins (3Z)- and (3E)-elatenynes having a 7,12-dibromo-6,9-cis-10,13-cis adjacent bis-tetrahydrofuran (THF) core. The present synthesis features a highly stereoselective, protecting group-dependent, chelate-controlled intramolecular amide enolate alkylation (IAEA) for the synthesis of key intermediate 7-hydroxy-6,7-cis-6,9-cis-THF intermediate 10, deployment of the sequential ate complex (n-BuLi/DIBAL-H) reduction/Keck allylation/cross metathesis (CM) protocol for the stereoselective introduction of the C(10)-C(15) unit, a sequential Sharpless asymmetric dihydroxylation (SAD)/intramolecular Williamson etherification for the construction of the 10,13-cis-THF ring, and a modified Nakata chloromethanesulfonate-mediated S_N2 displacement for the 7,12-dibromo functionality. Furthermore, our strategy based on chelate-controlled IAEA methodology would provide access to any member of the C₁₅ adjacent bis-THF acetogenin class.