Synthesis and Structural Implication of the JKLMN-Ring Fragment of Caribbean Ciguatoxin C‑CTX‑1

• Main Authors: Makoto Sasaki (71218), Kotaro Iwasaki (1306236), Keisuke Arai (5899403)
• Format: Other Non-Article Part of Journal/Newspaper
• Language: unknown
• Published: 2021
• Subjects: Biochemistry; Microbiology; Genetics; Molecular Biology; Neuroscience; Physiology; Pharmacology; Evolutionary Biology; Ecology; Marine Biology; Chemical Sciences not elsewhere classified; ciguatera fish poisoning; Caribbean Sea; Northeast Atlantic areas; enol ether; hydrogen atom transfer-based reduct.; resonance spectroscopic data; JKLMN-ring fragment; Synthesi; tetrasubstituted stereogenic center; silica gel-mediated epoxide ring op.; KLMN-ring enol phosphate; C-CTX; seven-membered α- hydroxy exo; Structural Implication; stereoselective construction; seven-membered M-ring; Northeast Atlantic
• Online Access: https://doi.org/10.1021/acs.joc.0c03031.s001

Synthesis of the JKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the causative toxin of ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. Key to the synthesis are a [2,3]-sigmatropic rearrangement to construct a seven-membered α-hydroxy exo -enol ether, stereoselective construction of an angular tetrasubstituted stereogenic center on the seven-membered M-ring by a hydrogen atom transfer-based reductive olefin coupling, Suzuki–Miyaura coupling of the KLMN-ring enol phosphate with a highly congested M-ring, and silica gel-mediated epoxide ring opening to form the J-ring. Comparison of the nuclear magnetic resonance spectroscopic data for the synthesized fragment with those for the natural product provided support for the formerly assigned structure of the N-ring in the right-hand terminal of C-CTX-1.