SYNTHESIS OF BRIDGEHEAD POLYCYCLIC 1,2-DIAMINES AND 2-AMINO ALCOHOL DERIVATIVES AS RIGID ACETYLCHOLINE ANALOGS

Oxidation of dioxime 2a with NBS gave 3 and 4. A chair-boat conformation has been established for 3 by X-ray diffraction analysis, while 4 seems to exist in a chair-chair conformation on the basis of NMR data. m-Chloroperbenzoic acid oxidation of dioximes 2 gave polycyclic dinitro compounds 7. In some oxidations of 2a, nitroso dimer 8 was isolated, its structure being established by X-ray diffraction analysis. Reduction of 7 with aluminium amalgam gave in good yields diamines 6, that were also obtained by reductive coupling from dioximes 2. Amino alcohols 14 were obtained by reductive coupling from monooximes 11. While 11a could be obtained in pure form from diketone 1a via 9a and 10a; hydrolysis of 10b to 11b failed. Azapolycyclic compounds 12 were obtained by hydrolysis of 10. Amino alcohol 14b was more appropriately prepared by reduction of nitro alcohol 15 obtained together with 7b by m-chloroperbenzoic acid oxidation of a mixture containing monooxime 11b and dioxime 2b. From the oxidation of a mixture containing 11a, nitro ketone 16 was isolated in low yield. Amino alcohols 14 and diamines 6 were also characterized as cyclic carbamates 13 or ureas 5. Rigid analogs of acetylcholine 20 and 21 were obtained from 14 by standard procedures, compounds 17 and 18 being detected as intermediates. Neither muscarinic nor antiacetyl-cholinesterase activity has been observed for compounds 20 and 21.

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