Philip Eskola

Determination of avermectins in plasma at nanogram levels using high-performance liquid chromatography with flourescence detection

An analytical method is described for the determination of the avermectins in plasma based upon high-performance liquid chromatography of fluorescent derivatives of these compounds. The analyte is isolated by adsorption chromatography on Florisil, dehydrated in an acetic anhydride-pyridine mixture, and the fluorophore is further separated by chromatography on silica gel in advance of introduction into a reversed-phase system. This method, which can be applied to samples containing as little as 0.2 ng drug per ml, has an accuracy of 5% mean relative error and a precision of 8% relative standard deviation. A study and discussion of several factors which affect the analytical reaction are included.

Discovery of novel avermectins with unprecedented insecticidal activity

A new class of insecticidal and antiparasitic agents, 4″-amino-4′-deoxy avermectins, has been developed by chemical modification of avermectin B1. The most effective of these compounds are 1500-fold more potent than avermectin B1 (abamectin) against the beet armywormSpodoptera exigua and show similar potency against other lepidopteran larvae.

4 -DEOXY-4 -AMINOAVERMECTINS WITH POTENT BROAD SPECTRUM ANTIPARASITIC ACTIVITIES

Abstract Reductive amination of 4″-oxo-5-O-tert-butyldimethylsilyl-avermectins with sodium cyanoborohydride and ammonium acetate gave an epimeric mixture of 4″-deoxy-4″-amino analogs with the epimeric, axial 4″-β-amino derivative as the major component. Acylation of the amino substituent gave highly active broad spectrum antiparasitic compounds, as determined in a sheep anthelmintic assay. 4″-Epi-acetylamino-4″-deoxyavermectin B 1 ( 12 ) was selected for further antiparasitic studies and is currently under development as a novel avermectin endectocide.

Synthesis of milbemycins from avermectins

The structure of the avermectins and the milbemycins were interrelated by the conversion of 22,23-dihydroavermectin B1a and B1b aglycones (4) into 13-deoxy-22,23-dihydroavermectin B1a aglycone (9) and 13-deoxy-22,23-dihydroavermectin B1b aglycone (11) corresponding to 26-ethyl milbemycin-α3 and milbemycin B-41D respectively via reduction of the protected 13-chloroaglycone derivatives.

Partial syntheses of avermectin Bla and ivermectin from avermectin B2a

4″,5-Bis-O-(tert-butyldimethylsilyloxyacetyl)-23-O-(4-methylphenyloxythiocarbonyl)avermectin B2a gave on pyrolysis and deprotection avermectin Bla, while reduction with tri-n-butyltin hydride followed by deprotection afforded 22,23-dihydroavermectin Bla (ivermectin).