The synthesis of Ventiloquinones J and F

Abstract

In chapter 2 the synthesis of ventiloquinone J is described, starting from vanillin, the key intermediate cis-3,4-dihydro-5,7-dimethoxy-10- methoxymethyleneoxy-1,3-dimethyl-1H-naphtho[2.3-c]pyran-6,9-dione was prepared in 19 steps by using inter alia Diels-Alder adduct formation, mild acetylation, oxymercuration and finally converted to ventiloquinone J in an overall yield of 0.5%. Protection of the C-10 position of the ventiloquinone J precursor was eventually effectively provided by the methoxymethyleneoxy (MOM) group which upon removal with acid treatment provided the hydroxy group in this position unambiguously in the final product. Attempts to effect this same protection using a benzyl group proved ineffective due to the extreme difficulty in separation of the cyclised stereoisomers; cis and trans 10- benzyloxy-3,4-dihydro -5,6,7,9-tetramethoxy-1,3-dimethyl-lH-naphthol2,3- c]pyrans In addition decomposition of the molecule occurred during the subsequent oxidation step affording low yields of the quinones and finally the unwanted isomer viz., the trans 1,3-dimethylpyran was the major product of the cyclisation. Protection of C-10 of the precursor to ventiloquinone J usingthe 2'-methoxyethoxymethyleneoxy (MEM) group proved problematic in that it was sensitive to the acidity of the silica gel stationary phase used for column chromatography, and that cyclisation of the intermediate alcohol, 2-(l'- hydroxyethyl)-4,5,6,8-tetramethoxy-l-(2'-methoxyethoxymethyleneoxy)-3- prop-2'-enylnaphthalene, Ied to a mixture of the corresponding cis and trans l,3-dimethyl pyrans in which the MEM protecting group had been lost in a combined crude yield of only 25%o. In addition all the MEM compounds showed considerable decomposition on standing. The synthesis of one of the initial target molecules, 6-hydroxy-7- methoxyeleutherin was not completed due to premature displacement of the required C-5 protecting groups employed in the naphthalene precursors upon acylations under Lewis acid Ventiloquinone F was successfully synthesised from 3,4,6- trimethoxybenzaldehyde in 12 steps making use of a Stobbe Condensation with methyl succinate to construct the desired oxygenated naphthalene nucleus. An overall yield of 9.5oh was obtained and its stereoisomer, isoventiloquinone F was also obtained in an overall yield of 10%.trans- 5-benzyloxy-3,4-dihydro-6,7,9'ttimethoxy-1,3-dimethyl-1I/- naphtho[2,3-c]pyran led to the formation of four pyranquinones which were successfully separated and purified. These were cis- and trans-5-benzyloxy- 3,4-dihydro-7-methoxy-1,3-dimethyl-lF/-naphthol2,3-clpytarr-6,9-diones as well as the corresponding cis and trans ortho quinone isomers.