Synthesis and antiviral bioactivities of novel chiral bis-thiourea-type derivatives containing α-aminophosphonate moiety

Abstract

Starting from 1-((1R,2R)-2-aminocyclohexyl)-3-substituted thioureas (3a-c) and substituted isothiocyanates (9a-d), chiral bis-thiourea derivatives containing -aminophosphonate moiety 10a-l were prepared and completely characterized by elemental analysis, physical and spectral (IR, 1 H NMR, 13 C NMR, 31 P NMR) data. The results of bioassay revealed that compounds 10a and 10e possessed appreciable curative bioactivities on cucumber mosaic virus (CMV) at 0.5 mg/mL in vivo (inhibitory rate = 60.3%, 64.8% respectively) and tobacco mosaic virus (TMV) at 0.5 mg/mL in vivo (inhibitory rate = 50.3%, 50.8% respectively), which were comparable to the values shown by standard reference (58.7%) and commercial product Ningnanmycin (56.3%), respectively. Chiral compound 10e displayed more potent antiviral activity (EC 50 = 0.149 mg/mL) than Ningnanmycin (EC 50 = 0.201mg/mL) against CMV. chiral bis-thiourea, -aminophosphonate moiety, antiviral activity, synthesis

Future direction of agrochemical development for plant disease in China

“…Li et al also used the chiral molecules derived from NPs (Zhang, Li, et al, ,2017Zhang, Wang, et al, 2018). Since 2009, Song and co-workers have been attempting to develop chiral antiviral agent by constructing a series of chiral phosphonate moieties using inexpensive, commercially available chiral amine (Chen et al, 2009), (R,R)-1,2diaminocyclohexane (Yang et al, 2011) and L-Boc-leucine (Liu et al, 2010) as the chiral building blocks. Recently, Li and co-workers synthesized two chiral succinate dehydrogenase inhibitors (SDHIs), (R)-2-chloro-N-(2-(4-ethyl-4,5dihydrooxazol-2-yl) phenyl)nicotinamide (SDHIs-1) and N-(2-((R)-4-ethyl-4,5-dihydrooxazol-2-yl) phenyl)-2-hydroxy-2-phenylacetamide (SDHIs-2) using chiral building blocks.…”

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…Likewise the aminophosphonic acids, they are able to inhibit enzymes involved in amino acids metabolism, and thus may generate various physiological responses, e.g., neuromodulatory activity [358]. Cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) are plant virus diseases which have become a serious problem in agriculture in recent years [359]. The commercially available product Ningnanmycin is commonly used against CMV and TMV, though with serious limitations resulting from its light and moisture sensitivity.…”

“…It was also found that the absolute configuration of isothiocyanates, used to form corresponding mono-and bis-thioureas, considerably affected the antiviral activity of tested compounds. Generally, mono-thiourea (S)-enantiomers were more effective against TMV than corresponding (R)-enantiomers [320], while the results for bis-thioureas against CMV appeared to be reversed: derivatives obtained from (R)-enantiomer of isothiocyanate were more active against the virus [359]. Molecules 2020, 25 Liu and co-workers prepared a series of chiral thioureas bearing t-leucine and αaminophosphonate moieties and evaluated their anti-TMV activity [360].…”

“…Moreover, it was more active against TMV than the reference compound Ningnanmycin. Ningnanmycin (left) and the most active bis-thiourea derivatives bearing α-aminophosphonate functional group [320,359].…”

“…Figure34. Ningnanmycin (left) and the most active bis-thiourea derivatives bearing αaminophosphonate functional group[320,359].…”