“…The double conjugate addition of activated methylene groups such as 245 to benzocycloheptadienone dicarboxylate 246 was reported and studied in detail by Föhlisch's group as a pratical access to bicylo[3.2.1]octanes 247 by ring closure of the methano bridge. …”
Section: Ring Closures Of the One-carbon Bridgementioning
“…The double conjugate addition of activated methylene groups such as 245 to benzocycloheptadienone dicarboxylate 246 was reported and studied in detail by Föhlisch's group as a pratical access to bicylo[3.2.1]octanes 247 by ring closure of the methano bridge. …”
Section: Ring Closures Of the One-carbon Bridgementioning
Zusammenfassung. Kondensation von 6,8-dimethoxycarbonpl-benzocycloheptan-7-on (4,5-Benzo-tropon-2,7-dicarbonsaure-dimethylester) (4) 4, mit Aceton-dicarbonsauredimethylester ergab 68% 1,5-Hydroxy, methoxy-Z,4,6,8-tetramethoxycarbonyl-lO, 1Oa-benzo-9-oxa-lOa-homoadamant-10-en (6) und 17% des bekannten 3,7-Dihydroxy-4,8, Zg, 6p-tetramethoxycarbonyl-9,10-benzo-bicyclo[3.3.2]dec-3,7,9-triens (7). Hydrolyse und Decarboxylierung uberftihrte den Tetraester 6 (wie schon fur 7 beschrieben) in 9,l0-Benzo-bicyclo[3.3.2]dec-9-en-3,7-dion (9). Aus den durch Spinsimulierung bestimmten lH-NMR.-Parametern wurde fur 9 die Bevorzugung des Sessel-Sessel-Konformers 9 cc abgcleitet.Bromierung des Diketons 9 mit vier Aquivalenten Brom lieferte 74% 1,5-Dihydroxy-Zp,4p-6,B, 8/3-tetrabrom-l0,10a-benzo-9-oxa-lOa-homoadamant-l0-en (10). Die homoadamantoide Struktur von 10 warwie schon friiher bei ahnlichen Systemcndurch hydratisierende Cyclisierung des primar gebildeten Tctrabrom-diketons entstanden; sie offenbarte sich in der Abwesenheit l) Some of these results have been communicated in a preliminary note [2], where a different numbering system and correspondingly different names have been used.
1)
2)Z. R. in Tomaten [Zj, Karottcn [3], in der Himbeere [4], im Schwarztce [5] und im Tabak [6]. Z.B. zur Synthese von Abscisinsaure [7] und Theaspiron [8].
Key Words: Intramolecular reductive coupling I Aluminium amalgam I Bridgehead polycyclic 1 ,2-diamines I Bridgehead polycyclic 2-amino alcohols I Rigid acetylcholine analogsOxidation 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 3 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 l l a could be obtained in pure form from diketone l a via 9a and 10a; hydrolysis of 10b to l l b 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 l l b and dioxime 2b. From the oxidation of a mixture containing l l a , nitro ketone 16 was isolated in low yield. Amino alcohols 14 and diamines 6were also characterized as cyclic carbamates 13 or ureas 5.Rigid analogs of acetylcholine 20 and 21 were obtained from 14 by standard procedures, compounds 13 and 18 being detected as intermediates. Neither muscarinic nor antiacetylcholinesterase activity has been observed for compounds 20 and 21.In connection with the synthesis of compounds that could be useful for the treatment of Alzheimer's disease, we were interested in compounds with antiacetylcholinesterase Compounds of general structure I (Scheme 1) can be considered as acetylcholine analogs containing a rigid lipophilic skeleton. Although it is known that conformationally rigid analogs of acetylcholine, having the ester and ammonium functions in an eclipsed arrangement, display no muscarinic activityk3], to the best of our knowledge nothing is about their potential activity as antiacetylcholinesterase agents, this stimulated us to undertook their synthesis.The retrosynthetic analysis of compounds I led to the polycyclic 1,2-diamines and 2-amino alcohols of general structure I1 which could be derived, via intermediates like 1V or V, from diketones 111, which can be easily obtained by the Weiss reactionL5].Only one synthesis of diamine 6a has been describedL61, but it involves a nine-step sequence with around 1% overall yield. However, several preparations of dinitro compound 7a are known. Thus, Walters et al. have describedL7I the oxidation of dioxime 2a with 1,3-dibromo-1,3,5-triazine-2,4,6( 1 H,3H,SH)-trione to give a mixture of bis-gem-bromo nitro compound 3 (54% yield) and tricyclic dinitro compound 7a (20% yield). Moreover, NaBH4[81 or electrochemicalf9] reduction of 3 gives 7a in good yield. In our hands, treatment of 2a with NBS as halogenatingoxidizing agent gave 3 in only 20-...
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