Precocene synthesis

A photochemical approach to the synthesis of precocenes /, II, and III, interesting as juvenile hormome inhibitors [177,178], has been deviced starting from the phenolic esters of 3-methylcrotonic acid. This is shown in Scheme 61 for the synthesis of precocene I (235) [179] and in Scheme 62 for the synthesis of precocenes II (238) and III (239) [180]. The rate of the cyclization process leading to chromanones, like 234 or 237, has been found to depend on the stereochemistry of the double bond. Thus, ring closure is more rapid for the trans than for the cis isomer, although no clear-cut trend can be established [181],... 

Isolation and identification of the two natural antijuvenile hormones revealed two simple chromenes 7-methoxy-2,2-dimethyl chromene and 6,7-dimethoxy-2,2-dimethyl chromene (Figure 3). Since these compounds induced precocious metamorphosis, we called them Precocene I and II respectively. Subsequently we found that both compounds had been previously identified and synthesized ( 15, 16, 17). We developed an efficient synthesis for these compounds shown in Figure 4. 

Figure 4. Synthesis of precocene. Reaction of an appropriate phenol with dimethyl acrylic acid and polypnosphoric acid (PPA) on the steam bath gives the chromanone in quantitative yield. Reduction with lithium aluminum hydride (LAH) and brief treatment with 4N hydrochloriic acid gives the chromene.

The suicidal bioactivation of the precocenes clearly suggests the possibility that, while the cytochrome P-450 system involved in JH synthesis may be quite specific with respect to the substrates it will accept, it represents a potentially important and viable target for future pest control agents. 

The rationale for design of proallatocidins related to chromenic structure of precocenes is discussed. Stabilization against environmental conditions and insect metabolic pathways, as well as modification of transport properties, sire some of the leads followed for the synthesis of more powerful insect growth regulators of this type. Some aspects of the chemistry of 3,4-epo-xyprecocenes are also examined. 

Kelly and Fuchs (1978) found an inhibition of trypsin synthesis after treatment of insects with precocene II and concluded that the retarded ovarial maturation is but a consequence of a general toxic state. 

Chromenes. - Continuing interest in the precocenes is shown by the synthesis, in good yield, of both I (120 R = H) and II (120 R = MeO), respectively, from the corresponding chromanone by reduction and dehydration, and of precocene II (120 R = MeO) from methoxyquinol and 2-methylbut-3-en-2-ol... 

The bioactivities of precocene I, 7-methoxy-2,2-dimethyl chromene, and precocene II, 6,7-dimethoxy-2,2-dimethyl chromene, are well established (Fig. (7)). These two compounds have been isolated from plants throughout the family Asteraceae [129-136, 154]. The chemical data for these compounds and references for their synthesis are compiled in Appendix IV, Tables 13 and 14. There is a wealth of information on the effects of these compounds on various insect species [42, 137]. For simplicity, we will focus on the effects of precocene II on the susceptible Hemipteran bug, Oncopeltus fasciatus. 

Chromenes.- Continuing interest in the precocenes and their biological action has stimulated further work on their synthesis. Precocene III (82) has been synthesized from a phenol, 3-methylbut-2-enal and titanium(IV) ethoxide93 and precocenes I and II were obtained by cyclization of the relevant 3-methoxyphenol with isoprene and dehydrogenating the resultant chroman with DDQ.94 Several new positional isomers of precocenes and related compounds have been synthesized and screened for insecticidal activity in a rice crop. Chromanones [such as (83)] were reduced with LAH to the chromanol which was efficiently dehydrated with a trace of toluene-4-sulphonic acid. Under some conditions, reduction gave dimeric... 

Miranda, M. A., Primo, J., and Tormos, R., A new synthesis of precocene 11 and precocene 111 based on the photo-Fries rearrangement of a sesamol ester, Heterocydes, 32, 1159, 1991. 

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