Methyl epijasmonate

Racemic methyl cucurbate and racemic methyl epijasmonate were synthesized via a thermal Alder-ene reaction (Scheme 40).99 The newly formed stereocenters are controlled by the existing protected hydroxyl group of 166 in an anti/syn relationship. 

This reaction can also be applied to the preparation of heterocyclic organocopper reagents such as 77 from readily available secondary alkyl iodides. Ring-closure in this case is catalyzed by Ni(acac)2 rather than by Pd(0), affording new heterocyclic molecules such as 78 (Scheme 2.26) [55]. These cyclization reactions are key steps in the preparation of such natural products as (-)-methylenolactocin 79 [57] and methyl epijasmonate 80 [58] (Scheme 2.27). 

Fig. 17 Total synthesis of methyl curcurbate 76 and methyl epijasmonate 77 via a radical-polar 5-exo cyclization/alkylation sequence...

Multiple cyclization reactions are possible, as well as preparation of heterocycles (Scheme 9-36) [65-70]. Several natural products, such as (+)-methyl epijasmonate (44) [69] (Scheme 9-37) and the antitumor antibiotic (—)-methylenolactocin 45 [68,74] (Scheme 9-38) have been prepared by this method. 

Hailes, H. C., Isaac, B., Hashim Javaid, M. Synthesis of methyl epijasmonate and cis-3-(2-oxopropyl)-2-(pent-2Z-enyl)-cyclopentan-1-one. Tetrahedron 2001,57,10329-10333. 

The esterification reaction of jasmonic acid with methyl alcohol was carried out in a high-pressure reactor to reduce epimerization. It was known that the cis-form of methyl jasmonate easily epimerized to the trans-form of methyl jasmonate under acid, base and high temperature conditions. The resulting methyl jasmonate mixture was recovered and purified by solvent extraction followed by fractional distillation. To improve the methyl epijasmonate concentration, additional steps of fractionation, such as the use of silica gel, were applied. 

The final natural and kosher methyl jasmonate mixture contains various optical isomers, including >5% of biologically active methyl epijasmonate. The methyl jasmonate mixture can be used in creating powerful fresh and sweet impressions in flavor and fragrance formulations, and additionally can be used in secondary and tertiary flavor enhancement. 

An efficient enantiomeric synthesis of (-)-methyl jasmonate [16] and (-l-)methyl epijasmonate [17] has been reported. The procedure makes use of a chiral cyclopen-tanoid building block that can easily be prepared from tartaric acid by phosphorus ylid chemistry (75). Jasmonic acid was also prepared by mixed Kolbe electrolysis (76). Methyl 3-methyljasmonate was synthesized from methyl jasmonate via methyl 3,7-dehydrojasmonate (77). 

The scope of the reaction can be extended to unsaturated alkyl bromides as substrates by using Ni(acac)2 as a catalyst instead of Pd(II) complexes. The use of Ni(acac)2 as a catalyst even with several polyfunctional alkyl iodides gives better results. Thus, in the key step for the synthesis of methyl epijasmonate 18, the alkyl iodide 19 undergoes a smooth cyclization using Ni(acac)2 and Et2Zn (Scheme... 

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