Natural Products Synthesis and Pesticide Science

From 1980 to 1988, we worked on the synthesis of brassinosteroids, another important group of phytohormones. Brassinolide was isolated in 1979 from Brassica napus in a small amoimt (4 mg from 40 kg of pollen) as a plant-growth promotor. We synthesized brassinolide [5], and also prepared non-natural 25-methylbrassinolide [6]. The latter was more bioactive than the former. These brassinosteroids were very easily metabolized by plants, and could not be used practically. Thus, natural products often remain only as prototypes of practically useful man-made products. 

We then worked on strigolactones such as (-i-)-strigol and (-i-)-orobanchol. The former was isolated from cotton plants in 1972 as a stimulant for the germination of Striga, while the latter was isolated in 1998 from Trifoliumpratense as a stimulant for the germination of Orohanche. Our synthesis made (-i-)-strigol readily available, and the structure of orobanchol could be determined [10]. Recently in 2005, 

5-deoxystrigol was shown to be the branching factor for arbuscular mycorrhizal fungus. 

In addition to pheromones (vide infra), we were interested in juvenile hormones (JHs), and synthesized ( )-juvabione [12] and (-t-)-juvabione [13-14]. JH mimics were later found to be useful as practical insect growth regulators (IGRs). We synthesized ( )-JH I [15], (-i-)-JH I [16] and unnatural (-)-JH I [17]. The naturally occurring (-i-)-JH I was 1.2 x lO times more active than (-)-JH I. Chirality plays an important role at JH receptor sites. 

I learned three things by synthesizing these bioactive natural products related to pesticides. Perhaps every pesticide chemist is familiar with the following points. First of all, natural products are often too complicated and fragile to be used as practical pesticides. Nevertheless, they can be the prototypes or lead compounds of new pesticides as in the cases of pyrethroids and juvenile hormones. Secondly, chirality plays a key role in the binding of these bioactive molecules at the active site. Thirdly, bioactivity observed in vitro or in vivo in lab tests may not always be reproduced in the field. 

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