Synthesis of Sesquichamaenol and Cyclization of Its Derivative

Abstract

The phenolic sesquiterpene ketone sesquichamaenol, isolated from the Benihi tree (Chamaecyparis formosensis Mathum. Cupressaceae), was synthesized through a new synthetic route and was, converted to some naphthalene derivatives. Starting from 3- (2-methoxy-5-methylbenzoyl) propionic acid [5], 5- (2-methoxy-5-methylpheny1)-6-methy1-2-heptanone [1b] was synthesized in 4 steps. Sesquichamaenol, 2- (1-isopropy1-4-oxopenty1)-4-methylphenol [1a] was obtained by demethylation of [1b] with hydrobromic acid. Reduction of [1b] produced 5- (2-methoxy-5-methylpheny1)-6-methy1-2-heptanol [9], which was then cyclized with hydrobromic acid to give a mixture of some tetrahydronaphthalenes. By heating the cyclized mixture with Pd-C, 1, 8-dimethyl-4-isopropylnaphthalene [3], its 1, 5-dimethyl isomer [14], 3, 4-dihydro-4, 5-dimethyl-8-isopropyl-1 [2H] -naphthalenone [16], its 4, 8-dimethy1-5-isopropyl isomer [17], and 2, 2, 5, 6-tetramethyl-2 H-naphtho[1, 8-bc]furan [18] were obtained. The reaction of 2-methyl-6- (2-methoxy-5-methylphenyl) -2-heptanol [10], an intermediate for the synthesis of elvirol [2] with hydrobromic acid also gave the same products.
These results indicate that the cyclization of [9] or [10] with hydrobromic acid proceeds via spiro-cyclic cation to give 1, 8-dimethy1-4-isopropyl-5-methoxy-1, 2, 3, 4-tetrahydronaphthalene [12A] and its 1, 5-dimethy1-8-methoxy isomer [13] The IR and NMR spectra of [12A] were different from those of [12B], which was obtained ag-a -by-product during the dehydrogenation of 3, 4-dihydro-1, 8-dimethy1-4-isopropyl-5-methoxynaphthalene [24B] BD. The transand cis-configuration are tentatively assigned to [12A] and [12B], respectively.