Frank S. Waksmunski

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.

A new broad-spectrum anthelmintic: 2-(4-Thiazolyl)-5-isopropoxycarbonylamino-benzimidazole

Es werden die Synthese sowie die biologischen Eigenschaften des neuen Anthelminticums 2-(4-Thiazolyl)-5-isopropoxycarbonylaminobenzimidazols beschreiben.

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.

An unusual twist in the synthesis and hydrolysis of the 23,24-epoxide of 22,23-dihydroavermectin B1a

Abstract Treatment of 4″,5-di-O-tert-butyldimethylsilyl(or phenoxyacetyl)-7-O-trimethylsilyl-avermectin B 2a ( 1a,b ) with diethylaminosulfur trifluoride (DAST) at 20AC in dichloromethane resulted in net elimination of water to yield 65% of the 23,24-olefin ( 2a,b ), 5–10% 23-fluoroavermectin derivative ( 3a,b ), and 20–25% of two rearranged products ( 4a,b:5a,b in a 2:1 ratio). The trisubstituted 23,24-olefin ( 2a,b ) was selectively epoxidized with m-chloroperbenzoic acid to give a mixture of alpha ( 6a,b major) and beta ( 7a,b minor) 23,24-epoxides in 64% yield. The acid catalyzed hydrolysis of epoxide 6a,b unexpectedly afforded hemiketal 9a,b as the major product (60%) and the usual 23,24-diol 10a,b as the minor product (6%). Subsequent Ley perruthenate oxidation of 9b produced lactone 13b in 15% yield. Lead tetracetate oxidation of 10a produced the desired cleavage product 14a in 40–50% yield.