Perillenal

Perilla ketone — see Ketone, 3-furyl isopentyl Perillene synthesis, 4, 668 Perinones, 1, 327, 337 Periodinane, bromo-synthesis, 1, 571 Periodinane, difluoro-reactions, 1, 571 Periodinanes cyclic... 

Furan-containing molecules are found in both natural products and pharmaceuticals. At one time, furfural was produced in great quantities from corncobs. Perillene, a secondary plant metabolite, is an example of naturally occurring furans. Furan is frequently used as a bioisostere of a benzene ring in medicinal chemistry. For example, Ranitidine (Zantac) marketed by Glaxo was one of the first blockbuster drugs with annual sales over 1 billion dollars. 

Disubstituted furans have been obtained from ketones using the reaction sequence shown in Scheme 24 (73JA250). The ketone is converted to the thioenol ether (117) which on reaction with dimethylsulfonium methylide yields the oxirane (118). Rearrangement leads to the dihydrofuran and thence to the 3,4-disubstituted furan (119). The terpenoid furans perillene (122) and dendrolasin (123) have been synthesized by treatment of the n-butylthiomethylene derivatives of the ketones (120) and (121) respectively with dimethylsulfonium methylide (Scheme 25). 

The furan ring is common in many naturally occurring terpenoid compounds methofuran (155), perillene (122) and dendrolasin (123) are examples. 

Such routes have been used for the synthesis of natural products terpenes such as egomaketone (3-(4-methyl-3-pentenoyl)furan, perillene, ar-turmerone and iso-ar-turmerone [341], ar-curcumene [152], artemisia and isoartemisia ketones [342, 343], damascone [344], macrolides such as maysine [345], and pheromones with the sex attractant of the pine saw-fly [346],... 

A variety of 3-substituted furans, including the natural perillene and dendrolasin, are obtained in good yields via reductive annulation of 2,2,2-trichloroethyl propargyl ethers... 

Reductive annulation of 1,1,1-trichloroethyl propargyl ethers using a catalytic amount of Cr(II) generated by Mn-Me3SiCl provided 3-substituted furans in high yields. Some natural products, such as perillene and dendrolasin, were prepared utilizing this procedure <02OL1387>. 

Reductive cyclization of trichloroethyl propargyl ethers using manganese and catalytic amounts of CrCl2 in the presence of TMSCl provided 3-substituted furans in high yields (Equation 27). The feasibility of this reaction has been demonstrated in the synthesis of the natural products perillene and dendrolasine <20020L1387>. 

The reaction was used to synthesize the naturally occurring furane perillene (2) from the ketone (I). 

Further details of Kondo s perillene (236) synthesis (Vol. 5, p. 43 Vol. 6, p. 16) have been publishedanother synthesis was based (Scheme 4) upon photochemical isomerization-lactonization of (237)/ Reduction and alkylation of 3-methyl-2-furoic acid with l-bromo-3-methylbut-2-ene gave (238) which was oxidatively decarboxylated with lead tetra-acetate-cupric acetate to rosefuran (239). ... 

Without the disadvantage of using diazo compounds in the first step, Wenkert s latest monoterpenoid syntheses would be most efficient approaches, and in any case represent novel routes to well-known materials. Nezukone (754) was the result of examining the reaction between butadiene and diazopyruvic ester catalyzed by rhodium tetraacetate. The major product of the addition was the cyclopropane 758 (Scheme 62). It was known that divinylcyclopropanes could be thermolyzed to cycloheptadienes (Vol.4, p.537, Ref.600). The Wittig product from 758 thus gives a cycloheptadiene, and subsequent steps are shown in the scheme. The last step involves Grignard addition to the ester function of the enolate, then loss of water and redistribution of the double bonds.(Further examples of the use of diazo compounds will be found under perillene in the section on furans.)... 

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