Synthesis of the ABCDEFG ring system of maitotoxin.
Maitotoxin (1) continues to fascinate scientists not only because of its size and potent neurotoxicity but also due to its molecular architecture. To provide further support for its structure and facilitate fragment-based biological studies, we developed an efficient chemical synthesis of the ABCDEFG segment 3 of maitotoxin. (13)C NMR chemical shift comparisons of synthetic 3 with the corresponding values for the same carbons of maitotoxin revealed a close match, providing compelling evidence for the correctness of the originally assigned structure to this polycyclic system of the natural product. The synthetic strategy for the synthesis of 3 relied heavily on our previously developed furan-based technology involving sequential Noyori asymmetric reduction and Achmatowicz rearrangement for the construction of the required tetrahydropyran building blocks, and employed a B-alkyl Suzuki coupling and a Horner-Wadsworth-Emmons olefination to accomplish their assembly and elaboration to the final target molecule.
Nicolaou
K C
KC
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Aversa
Robert J
RJ
Jin
Jian
J
Rivas
Fatima
F
D005663:Furans / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry*; D035964:Oxocins / Q000138:chemical synthesis* / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D000095702:Polyether Toxins
D005663:Furans; D008387:Marine Toxins; D035964:Oxocins; D011083:Polycyclic Compounds; C020394:maitotoxin; D000095702:Polyether Toxins; C039281:furan