Chapter 25
Rhamnose Replacement Analogs of Spinosyn A
Downloaded by PENNSYLVANIA STATE UNIV on June 17, 2012 | http://pubs.acs.org Publication Date: July 29, 2001 | doi: 10.1021/bk-2002-0800.ch025
P. B . Anzeveno and F . R . Green, III Discovery Research Center, Dow AgroSciences L L C , 9330 Zionsville Road, Indianapolis, IN 46268-1053
This chapter describes the syntheses and bioactivities against tobacco budworm (TBW) and two-spotted spider mite (TSSM) of a number of rhamnose replacement analogs of spinosyn A ; compounds in which the rhamnose has been replaced by other sugars, methoxybenzoic acids, methanol and 2-methoxyethanol. The sugar replacements include α -and β-linked pyranoses and furanoses: D-rhamnose, 2-deoxyL-rhamnose, L-lyxose, L-ribose, L-mannose, L - ( 3 - 0 - L -rhamnosyl)rhamnose and N-demethyl-D-forosamine. The D -sugar-, β-anomeric sugar-, furanose sugar-, α, α'disaccharide, forosaminyl- and non-sugar analogs were inactive against both T B W and T S S M . The α,β'-disaccharide retained activity against T B W . Removal of the 6-methyl group (L-lyxose analog) did not significantly affect activity, while addition of a methoxyl to the 6-methyl group (L -mannose analog) led to an ~ 10-fold enhancement of T B W activity. The 2-deoxyrhamnose analogs showed somewhat enhanced T B W activity but no T S S M activity.
The spinosyns (Figure 1) are a new family of insecticidal, fermentationderived macrocyclic lactones produced by a novel actinomycete, Saccharopolyspora spinosa (i). The major products produced are spinosyn A and spinosyn D which are present in an approximate 85:15 ratio and which together account for over 90% of the active material (2). Currently, more than 24 natural spinosyns have been isolated and characterized. These differ 262
© 2002 American Chemical Society
In Synthesis and Chemistry of Agrochemicals VI; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.
Downloaded by PENNSYLVANIA STATE UNIV on June 17, 2012 | http://pubs.acs.org Publication Date: July 29, 2001 | doi: 10.1021/bk-2002-0800.ch025
263 predominantly in the methylation patterns of the amine and hydroxyl groups and to a lesser extent in the C-methylation of the nucleus. These natural factors have been evaluated and their relative insecticidal activities reported (3). When tested against a wide range of insect pests, the spinosyns were found to be extremely effective at controlling primarily lepidopteran insects, major agronomic pests in such crops as cotton and vegetables. Moreover, most other characteristics necessary for effective pest control such as environmental compatibility, speed of action and low toxicity both to mammals and beneficial insects were ideal. The spinosyns appear to exert their effects on insects through alteration of nicotinic acetylcholine receptor function by a mechanism different from other nicotinic agents such as imidacloprid (4). Some effects on the GABA-gated cloride channel system have also been observed.
spinosyn A spinosyn D
R=H R = CH
3
Figure l.The two major spinosyns
Chemical Modification of the Spinosyns The insecticidal spectrum exhibited by the spinosyns is quite broad: control of lepidoptera, diptera, mites, aphids, cockroaches, termites and many other species has been seen. However as mentioned above, the greatest activity is against lepidopteran pests such as tobacco budworm and beet armyworm. At Dow AgroSciences, an extensive chemical modification program was undertaken to identify analogs with enhanced and/or broader spectrum activities. The general spinosyn structure (Figure 2) shows the degree of complexity of the molecule and also suggests sites of potential modification. Each of these sites has been investigated and a general review of both the chemistry and the effects of particular modifications on insecticidal activity has appeared (5).
In Synthesis and Chemistry of Agrochemicals VI; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.
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