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The reaction of thebaine with 2-bromo-6-methyl-1,4-benzoquinone regioselectively afforded 6,18- endo-etheno-9-methyldihydrothebainehydroquinone. Iodination of 6,18- endo-ethenodihydrothebainehydroquinones with N-iodosuccinimide in trifluoroacetic acid was also selective, and the corresponding 1-iodo derivatives were formed. The main reaction pathway in the halogenation of 6,18- endo-ethenodihydrothebainehydroquinone with iodine chloride was chlorination of the fused hydroquinone fragment. The Sonogashira reaction of 1-iodo-6,18- endo-ethenodihydrothebainehydroquinones with trimethylsilylacetylene and subsequent desilylation gave 1-ethynyl-6,18- endo-ethenodihydrothebainehydroquinones. 1-[3-(4-R-Piperazin-1-yl)-propynyl]- and 1-{3-[2-(pyridin-3-yl)piperidin-1-yl]propynyl}-6,18- endo-ethenodihydrothebainehydroquinones were synthesized by the Mannich reaction of acetylenic derivatives of dihydrothebainehydroquinone with piperazine and anabasine in the presence of formaldehyde, catalyzed by copper(I) compounds. The reaction of 1-iodo-6,18- endo-ethenodihydrothebainehydroquinone with N-methylpiperazine and formaldehyde was accompanied by copper-catalyzed oxidative homocoupling. [ABSTRACT FROM AUTHOR]

The iodination of N′-substituted (2,5-dioxopyrrolidino)[3,4- h]-6,14- endo-ethenotetrahydrothebaines with N-iodosuccinimide in trifluoroacetic acid afforded depending on the excess of the reagent either 1-iodo- or 1,2-diiodo endo-ethenotetrahydrothebaines. The Sonogashira reaction of 1-iodo-6,14- endo-ethenotetrahydrothebaines with trimethylsilylacetylene led to the formation of N′-substituted 1-(trimethylsilylethynyl)-(2,5-dioxopyrrolidino)-[3,4- h]-6,14- endo-ethenotetrahydrothebaines whose desilylation cleanly furnished the corresponding 1-ethynyl endo-ethenotetrahydrothebaines. The Mannich reaction of the acetylene derivatives of tetrahydrothebaine with amines and formaldehyde catalyzed by compounds of Cu(I) provided 1-[3-(morpholin-4-yl)propynyl]-, 1-[3-(4-methylpiperazin-1-yl)propynyl]-, and 1-[3-(4- tert-butoxycarbonylpiperazin-1-yl)propynyl]-(2,5-dioxopyrrolidino)[3,4- h]-6,14- endo-ethenotetrahydrothebaines. [ABSTRACT FROM AUTHOR]

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C7-C8 bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′ H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[( E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo- endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform. [ABSTRACT FROM AUTHOR]