Biomimetically inspired total synthesis and structure activity relationships of 1-O-methyllateriflorone. 6 pi electrocyclizations in organic synthesis.
The total synthesis of 1-O-methyllateriflorone (2) is described. The construction of the cage-like domain of the molecule involved a biomimetic Claisen/Diels-Alder cascade, whereas the novel spiroxalactone framework was generated by an intramolecular Michael reaction within precursor 16a involving the carboxylate residue as the nucleophile. This finding might bear on the biosynthetic pathway by which nature forms lateriflorone. Described herein is also an interesting cascade sequence involving facile 6 pi electrocyclizations which leads to complex benzopyran systems. The biological evaluation of a small library of lateriflorone analogues and related systems establishing the first SAR within this class of compounds is also included. Among the most active compounds against tumor cells are 2, 16b, 56, 58, and 59.
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
Sasmal
Pradip K
PK
Xu
Hao
H
D001578:Benzopyrans / Q000737:chemistry; D032701:Biomimetics; D045744:Cell Line, Tumor; D003500:Cyclization; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D007455:Iodine / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C482882:1-O-methyllateriflorone; D001578:Benzopyrans; D011083:Polycyclic Compounds; D013141:Spiro Compounds; D007455:Iodine