Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents.

Dong Ma,Jun Wu,Yi-Tao Yan,Yang Yin,Ying-Lu Chen

doi:10.1039/d1ra02663a

Abstract

The synthesis of highly diverse libraries has become of paramount importance for obtaining novel leads for drug and agrochemical discovery. Herein, the step-economical diversity-oriented synthesis of a library of various pyrimidine–N-heterocycle hybrids was developed, in which a 4,6-dimethoxypyrimidine core was incorporated into nine kinds of N-heterocycles. A total of 34 structurally diverse compounds were synthesized via a two-step process from very simple and commercially available starting materials. Further, in vivo biological screening of this library identified 11 active compounds that exhibited good post-emergence herbicidal activity against D. sanguinalis at 750 g ai per ha. More importantly, pyrimidine–tetrahydrocarbazole hybrid 5q showed good to excellent herbicidal activity against five test weeds at the same dosage. Pyrimidine–tetrahydrocarbazole hybrids represent a novel class of herbicidal agents that may become promising lead compounds in the herbicidal discovery process.

Highlights

Pyrimidine as a core structure widely exists in natural products.[1]
Bispyribac-sodium (BS) is an inhibitor of acetohydroxyacid synthase (AHAS; EC 2.2.1.6), the rst enzyme involved in the branched-chain amino acid biosynthesis pathway.[10]
BS is a broad spectrum pyrimidinyl carboxy herbicide that has been used in the transplanted and direct seeded rice crops for selective post-emergence control of grasses, sedges and broad-leaved weeds.10a,11 Bensulfuron-methyl is an AHAS-inhibiting herbicide belonging to the sulfonylurea class

Summary

Introduction

Pyrimidine as a core structure widely exists in natural products.[1]. It has shown prominent pharmaceutical and agricultural activity,[2] and acts as anti-cancer,[3] anti-HIV,[4] and anti-microbial[5] agents, insecticides,[6] fungicides[7] and herbicides.8 4,6-Dimethoxypyrimidine is a key structural motif commonly employed in herbicide molecular design in the quest for novel highly active herbicides[9] (Fig. 1a). Preliminary biological tests showed that some compounds exhibited good to signi cant herbicidal activity. When a mixture of 1 and 2a was heated at 130 C for 30 min under solvent-free condition, the desired product 3a was obtained in only 40% yield (Table 1, entry 1).

Results

Conclusion