Tatsushi Ohsawa

Studies on the syntheses of heterocyclic compounds. Part 878. Synthesis of (±)-camptothecin and (±)-10-methoxycamptothecin via enamine annulation

Synthesis of (±)-camptothecin (1) and (±)-10-methoxycamptothecin (2) was achieved via enamine annelation as a key step. Condensation of 3,4-dihydro-1-methyl-β-carbolines (9) and (10) with unsaturated tetra-esters (6) and (7) followed by reduction gave the indolo[a]quinolizin-4-ones (12) and (13). Photo-oxygenation of (12) and (13) and subsequent base treatment produced the indolizino[1,2-b]quinolones (16) and (17), which were converted into the pyridones (20) and (24). The former (20) had been correlated to (±)-camptothecin, while the latter (24) was transformed into (±)-10-methoxycamptothecin by application of the established method.

Studies on the syntheses of heterocyclic compounds. Part 865. A novel synthesis of indole derivatives by intramolecular nucleophilic aromatic substitution

Cyclisation of N-(2-bromo-4,5-dimethoxyphenethyl)acetamide (6) afforded 1-acetyl-2,3-dihydro-5,6-dimethoxy-1H-indole (13) by intramolecular nucleophilic aromatic substitution using sodium hydride and cuprous halide in dimethylformamide. The dihydroindoles (14), (15), and (16) were also synthesised from the corresponding amides (8) and (10) and the carbamate (12) in a similar manner. The dihydroindoles (13), (14), and (16) were converted into the indoles (20) and (21) in excellent yield by oxidation and subsequent alkaline hydrolysis. The 2-oxindoles (26) and (27) were also prepared under similar reaction conditions from the phenylacetamide (24) and (25).

Studies on the syntheses of heterocyclic compounds. Part 738. Photo-oxygenation of 9-oxo-9H-pyrrolo[1,2-a]indoles

Photo-oxygenation in methanol of 7-methoxy-6-methyl-9-oxo-9H-pyrrolo[1,2-a]indole (10), prepared from 2-bromo-5-methoxy-4-methylbenzaldehyde (5)via 2-(2-bromo-5-methoxy-4-methylbenzoyl)pyrrole (8), formed (±)-9,9a-dihydro-3α-hydroperoxy-9-oxo-7,9aβ-dimethoxy-6-methyl-3H-pyrrolo[1,2-a]indole (14) and the (±)-3α-hydroxy-compound (16). The corresponding 9a-ethoxy-(20) and 9a-isopropyloxy-derivatives (21) were obtained from the photo-oxygenation of compound (10) in ethanol and isopropyl alcohol, respectively. The dye-sensitized photo-oxygenation of 9-oxo-6,7-dimethoxy-9H-pyrrolo[1,2-a]indole (11) was also carried out in methanol.