Synthesis of a radiolabeled enniatin cyclodepsipeptide [3H-methyl]JES 1798

Abstract

SummaryFor receptor binding studies and the elucidation of the mode of action of the potent anthelmintic compound JES 1798 a tritium labeled compound at very high specific activity was necessary. Tritium was introduced by methylation of the N-demethyl precursor JES 2314. The identity of m-methyl-3H]JkS 1798 was determined by mass spectrometry.After synthesis and purification, 535 pg [N-methyl-3H]JES 1798 were available at a specific activity of 84 Ci/mmol (3.1 1 TBqhmol) as determined by mass spectrometry.The total activity was 80 mCi (2.96 GBq).

Cyclooctadepsipeptides – a new class of anthelmintically active compounds

“…Moreover, by ring-shortening of PF1022A, synthetic enniatins can be obtained (Jeschke et al 1999); and a tritium-labeled synthetic enniatin has also been obtained (Pleiss et al 1996). Interestingly, PF1022A shows polymorphism (Kachi et al 1998).…”

Natural products as anthelmintics: safeguarding animal health

“…The enniatins have been reported to exhibit a range of biological properties, both detrimental and benecial, including as mycotoxins/cytotoxins and as inhibitors of ion channels, malaria, tuberculosis, selected enzymes and plant fungal pathogens. 307,308 Futher studies have elaborated biological mechanism of action of both enniatins 301,309 and related beauvericins. 312 The peptaibol cephaibol A (5.67) was reported in 2001 from Acremonium tubakii DSM 12774, 313 and its structure conrmed by X-ray crystallography in 2003.…”

“…In a 1996 study into synthetic analogues and mode of action of enniatins A ( 5.62 ), A 1 ( 5.63 ), B ( 5.64 ) and B 1 ( 5.65 ), and the closely related analogue beauvericin ( 5.66 ) demonstrated that they were active in vitro against H. spumosa ( 5.63 , EC 75–99 1 μg mL −1 ; 5.64 , EC <50 10 μg mL −1 ; 5.65 , EC 75–99 10 μg mL −1 ; 5.66 , EC <50 100 μg mL −1 ), N. brasiliensis ( 5.62 , EC 75–99 5 μg mL −1 ; 5.63 , EC <50 100 μg mL −1 ; 5.64 , EC 50–75 10 μg mL −1 ; 5.65 , EC 75–99 10 μg mL −1 ; 5.66 EC 75–99 100 μg mL −1 ) and T. spiralis ( 5.62 , EC 100 5 μg mL −1 ; 5.63 , EC 100 10 μg mL −1 ; 5.64 , EC 75–99 1 μg mL −1 ; 5.65 , EC 75–99 1 μg mL −1 ; 5.66 , EC 50–75 100 μg mL −1 ). 309 Exploring the structure activity relationship, synthetic enniatin stereoisomers 310 and other analogues 311 reduced worm burden (faecal egg count) when orally administered to an H. contortus sheep infection model (EC >95 0.05 to 0.5 mg kg −1 ). The enniatins have been reported to exhibit a range of biological properties, both detrimental and beneficial, including as mycotoxins/cytotoxins and as inhibitors of ion channels, malaria, tuberculosis, selected enzymes and plant fungal pathogens.…”

Reprogramming the Biosynthesis of Cyclodepsipeptide Synthetases to Obtain New Enniatins and Beauvericins

“…[40] For the hexadepsipeptides enniatin and beauvericin, nematicidal activity was reported only at concentrationso f1to 100 ppm. [41] As our new compounds are structuralh ybrids of enniatin, beauvericin, and PF1022, we tested them as potential nematicides. Because of the potential relevance of cyclo-octadepsipeptides for the treatment of human filariasis, [42] we chose microfilariae of the heartworm Dirofilaria immitis,w hich causes severe symptoms in animals, for efficacy evaluation.…”