Cyclorocaglamide, the First Bridged Cyclopentatetrahydrobenzofuran, and a Related “Open Chain” Rocaglamide Derivative from Aglaia oligophylla

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2003-01, Vol.66 (1), p.80-85
• Main Authors: BRINGMANN, Gerhard, MüHLBACHER, Jörg, MESSER, Kim, DREYER, Michael, EBEL, Rainer, NUGROHO, Bambang W., WRAY, Victor, PROKSCH, Peter
• Format: Article
• Language: English
• Subjects: Animals; Benzofurans - chemistry; Benzofurans - isolation & purification; Benzofurans - pharmacology; Biological and medical sciences; Bridged-Ring Compounds - chemistry; Bridged-Ring Compounds - isolation & purification; Bridged-Ring Compounds - pharmacology; Chromatography, High Pressure Liquid; Circular Dichroism; Cyclopentanes - chemistry; Cyclopentanes - isolation & purification; Cyclopentanes - pharmacology; Feeding Behavior - drug effects; General pharmacology; Insecticides - chemistry; Insecticides - isolation & purification; Insecticides - pharmacology; Larva - drug effects; Medical sciences; Meliaceae - chemistry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Spodoptera - drug effects; Stereoisomerism
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np020291k

Two rocaglamide-related natural products, the previously known compound 6-demethoxy-10-hydroxy-11-methoxy-6,7-methylendioxyrocaglamide (3), and cyclorocaglamide (4), its 8b,10-anhydro analogue, have been isolated from the tropical plant Aglaia oligophylla. Compound 4 is the first bridged cyclopentatetrahydrobenzofuran natural product, and it exhibited a CD spectrum virtually opposite that of all the other rocaglamide natural products known so far, but it still has the same absolute configuration at all stereogenic centers of the basic molecular framework. This was shown unequivocally by quantum chemical CD calculations (here based on molecular dynamics-weighted force field structures) and was finally confirmed experimentally, by a "biomimetic-type" cyclization of 3 to give 4, with the expected "inversion" of the CD spectrum. The opposite chiroptical properties of 3 and 4, despite their homochiral character, underline the necessity of handling chiroptical data with the greatest care, e.g., by simulating them by quantum chemical CD calculations. Compound 3 exhibited an LC(50) of 2.5 ppm when evaluated against neonate larvae of Spodoptera littoralis, while 4 was inactive in this assay up to 100 ppm.