Avocadofurans and their tetrahydrofuran analogues: comparison of growth inhibitory and insecticidal activity.

The importance of the double bonds in the furan ring of avocadofurans with relation to their insecticidal activity was examined. The insecticidal activity of two naturally occurring avocadofurans, 2-(pentadecyl)furan and 2-(heptadecyl)furan, was compared to the toxicity of five tetrahydrofurans with alkyl chains at position 2 and varying side chains from 14 to 18 carbons. We found that eliminating the sites of unsaturation in the furan ring of avocadofurans significantly reduced the detrimental effects on the mortality and growth of the generalist insect herbivore Spodoptera exigua. In 7-day bioassays, S. exigua larvae were significantly more affected when fed a diet containing avocadofurans as compared to a larvae fed diet treated with the analogous tetrahydrofurans. Although larvae fed with the tetrahydrofurans showed reduced growth as compared to controls, larval mortality was not significantly increased. We conclude that the double bonds in the furan ring of avocadofurans play an important role in their insecticidal effects.

Alkylfurans: effects of alkyl side-chain length on insecticidal activity.

The insecticidal activity of five alkylfurans against the generalist insect herbivore beet armyworm, Spodoptera exigua, was examined. Two naturally occurring compounds, the avocadofurans 2-(pentadecyl)furan (1) and 2-(heptadecyl)furan (2), previously isolated from specialized avocado idioblast oil cells, and three homologues, 2-(tetradecyl)furan (3), 2-(hexadecyl)furan (4), and 2-(octadecyl)furan (5), were synthesized. Bioassays of alkylfurans 1-5 using a 9-day diet-incorporation initiated with neonates showed that all alkylfurans tested significantly increased S. exigua larval mortality and reduced larval weights, with maximal biological activity detected among the naturally occurring alkylfurans 1 and 2.

14-epi stereoisomers of 25-hydroxy- and 1 alpha,25-dihydroxyvitamin D3: synthesis, isomerization to previtamins, and biological studies.

The C-14 epimers of vitamin D, 14-epi-25-hydroxyvitamin D3 (4) and 14-epi-1 alpha, 25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, although epimerization at C-14 shifts the equilibrium of the triene chromophore to the previtamin form. The in vivo biological activities of 4, 4', 5, and 5' in the chick in terms of their ability to elicit intestinal calcium absorption and bone calcium mobilization were determined. These vitamin D analogues, the first in the natural steroid series modified at the C-14 position, were essentially devoid of activity. The relative competitive indices (RCIs), derived in an in vitro assay reflecting the ability of these analogues to bind to the chick intestinal nuclear receptor, were determined. Analogues 4, 4', 5, and 5' had RCI values of 0.08, 0.01, 15, and 1.6, respectively, in comparison to the natural ligand, 1 alpha, 25-dihydroxyvitamin D3 (3), whose value is 100 by definition. Thus, the in vivo and in vitro data were somewhat at variance, particularly for 5, which bound significantly to the chick intestinal receptor. In vitro binding studies with the human serum vitamin D binding protein (DBP) were also conducted. The RCI values for human DBP reflects the ability of an analogue to bind to this protein in comparison to the hormone 3, whose value is 100. The measured RCI values for 4, 4', 5, and 5' were 3450, 90, 12, and 2.2, respectively. It is noteworthy that analogue 4 binds approximately 35 times more effectively than the parent hormone 3, but approximately 20 times less effectively than 25-hydroxyvitamin D3 (2).