Ikuo Iijima

Synthesis utilising the β-carbonyl system. Part 5. A synthesis directed towards the fungal xanthone bikaverin

2-[3-(1-Oxo-3-aminobut-2-enyl)-7-methoxy-5-methyl-4-oxo-4H-benzopyran-2-ylmethyl]dioxolans, (7a and b), with an ethoxycarbonylmethyl or methyl substituent on the 2-position, have been synthesised starting with three precursors corresponding to β-tetra-, β-tri-, and β-di-carbonyl compounds. Acid treatment of the 2-ethoxycarbonylmethyl compound (7a) afforded ethyl 3-(1-hydroxy-6-methoxy-3,8-dimethyl-9-oxoxanthen-2-yl)-3-oxopropanoate (13a) as the major product together with three minor products, including ethyl 2-acetyl-1-hydroxy-6-methoxy-8-methyl-9-oxoxanthen-3-ylacetate (11); whereas the 2-methyl compound (7b) yielded 2-acetyl1-hydroxy-6-methoxy-3,8-dimethylxanthen-9-one (13b), exclusively. The structures of (13a) and (17) were cosnfirmed by 13C n.m.r. Spectroscopy using the long-range selective proton-decoupling (LSPD) method. Formation of (13a) from (7a) is explained in terms of a Wessely–Moser rearrangement of the intermediary benzopyranone (9a) or the xanthone (10a) under mild acidic conditions. Base-catalysed cyclisation of the xanthone3-acetate (11) gave 8,10,11-trihydroxy-3-methoxy-1-methyl-12H-benzo[b]xanthen-12-one (20) in excellent yield.

Synthetic studies on pyrroloquinolines. Part IV. Preparation hydrogenated 3a-methylpyrrolo[3,2-c]quinolines

Removal of the phthaloyl group from 7-chloro-3-methyl-3-(2-phthalimidoethyl)quinoline-2,4-dione (2) followed by cyclization gave 7-chloro-3,5-dihydro-3a-methyl-2H-pyrrolo[3,2-c]quinolin-4-(3aH)-one (3), the CN bond of which was reduced stereospecifically to give the 3a,9b-trans-compound (4) with sodium borohydride at –30 to –20°. Although treatment of compound (4) with lithium aluminium hydride mainly afforded the abnormal reduction product, 7-chloro-3,3a,4,5-tetrahydro-3a-methyl-2H-pyrrolo[3,2-c]quinoline (7), treatment with aluminium hydride simply reduced the oxo-group to give the trans-hexahydropyrroloquinoline (9). The cis-isomer (10) was obtained, along with the trans-isomer (9), by reduction of compound (7) with sodium borohydride.

Synthetic studies on pyrroloquinolines. Part III. Improved synthesis of 7-chloro-2,3-dihydro-4-methoxy-1H-pyrrolo[2,3-b]quinoline and its conversion into 3a,10b-diazacyclopenta[jk]phenanthrene derivatives

3-(2-Aminoethyl)-7-chloro-4-methoxy-2-quinolone (7) was prepared by methylation of 7-chloro-4-hydroxy-3-(2-pnthalimidoethyl)-2-quinolone and removal of the phthaloyl group. Cyclization of the 3-(2-acetamidoethyl) derivative (9) gave, after hydrolysis, the pyrrolo[2,3-b]quinoline (12). An addition reaction with ethyl acrylate followed by reduction with aluminium hydride led to the pyrroloquinolin-1-ylpropanol (14), which was cyclized to the diazacyclopenta[jk]phenanthrene (16)via the quaternary salt (15). Hydrolysis of compound (16) gave the 6-ketone (17), whose structure was confirmed by its n.m.r. spectrum.