Hydantocidin

Novel one-pot multicomponent synthesis of 2-pyrimidinamine derivatives can be achieved via green chemistry, using Cu(II)-tyrosinase enzyme (Cu-Tyr) as a catalyst. This method offers mild reaction conditions and a high yield of derivatives. We synthesised several compounds in this manner and evaluated their larvicidal, and antifeedant activities. Out of the synthesised derivatives, compound 3, with a median lethal dose (LD50) of 21.43 µg/mL, was highly active against Culex quinquefasciatus, compared to compounds 1a-m and 2, and the control, hydantocidin. Compounds 1j, 1d, and 1e were low active against C. quinquefasciatus with LD50 values of 78.46, 78.59, and 79.54 µg/mL, respectively. In antifeedant screening, compounds 1j, 1l, and 2 generated 100% mortality within 24 h against Oreochromis mossambicus at 100 µg/mL, where toxicity was determined as the ratio of the number of dead and live fingerlings (%) at 24 h. In contrast, compounds 1a-f, 1i, 1m, and 3 were less toxic to O. mossambicus as compared to the control, dibromoisophakellin. Therefore, compound 3 had high larvicidal activity against C. quinquefasciatus and was less toxic to non-target aquatic species. Molecular docking studies also supported the finding that compound 3 was an effective larvicide with more inhibition ability than the control hydantocidin (-9.6 vs. -6.1 kcal/mol).

Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin.

Spironucleosides are a type of conformationally restricted nucleoside analogs in which the anomeric carbon belongs simultaneously to the sugar moiety and to the base unit. This locks the nucleic base in a specific orientation around the N-glycosidic bond, imposing restrictions on the flexibility of the sugar moiety. Anomeric spiro-functionalized nucleosides have gained considerable importance with the discovery of hydantocidin, a natural spironucleoside isolated from fermentation broths of Streptomyces hygroscopicus which exhibits potent herbicidal activity. The biological activity of hydantocidin has prompted considerable synthetic interest in this nucleoside and also in a variety of analogues, since important pharmaceutical leads can be found among modified nucleoside analogues. We present here an overview of the most important advances in the synthesis of spironucleosides.