On the basis of the structure of natural product harmine, lead compound 18, and the structure of compounds in part 1, a series of thiophosphoramide derivatives 1–17 were designed and synthesized from various amines in one step. Their antiviral and antifungal activities were evaluated. Most of the compounds showed significantly higher antiviral activity against tobacco mosaic virus (TMV) than commercial virucide ribavirin. Compound (R,R)-17 showed the best anti-TMV activity in vitro (70%/500 μg/mL and 33%/100 μg/mL) and in vivo (inactivation effect, 68%/500 μg/mL and 30%/100 μg/mL; curative effect, 64%/500 μg/mL and 31%/100 μg/mL; protection effect, 66%/500 μg/mL and 31%/100 μg/mL), which is higher than that of ningnanmycin and lead compound 18. The antiviral activity of (R,R)-17·HCl is about similar to that of (R,R)-17. However, the antifungal activity of (R,R)-17·HCl against Puccinia sorghi is slightly lower than that of (R,R)-17. The systematic study provides compelling evidence that these simple thiophosphoramide compounds could become efficient antiviral and antifungal agents.

A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to be important but not the more the better. The optimal compound (R,R)-20 showed the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500 μg/mL and 39%/100 μg/mL; inactivation activity, 71%/500 μg/mL and 35%/100 μg/mL; curative activity, 73%/500 μg/mL and 37%/100 μg/mL; protection activity, 69%/500 μg/mL and 33%/100 μg/mL), which is significantly higher than that of Ningnanmycin. The systematic study provides strong evidence that these simple thiourea derivatives could become potential TMV inhibitors.

On the basis of the structure of natural product (−)-incrustoporin (1), a series of lactone compounds 4a–i and 5a–i were designed and synthesized from nitroolefin. The antiviral and antifungal activities of these compounds were evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4-position result in large differences in bioactivities. Compounds 4 exhibited significantly higher antiviral activity against tobacco mosaic virus (TMV) than dehydro compounds 5. However, the antifungal activity of 4 is relatively lower than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity emerged as new antiviral lead compounds. Compounds 5d–g showed superiority over the commercial fungicides chlorothalonil and carbendazim against Cercospora arachidicola Hor at 50 mg kg–1. The present study provides fundamental support for the development and optimization of (−)-incrustoporin derivatives as potential inhibitors of plant virus and pathogenic fungi.