R. Granados

Azabicyclo[3.2.1]octane derivatives

Abstract The synthesis of the 8,12-methanoazepino[2,1-a]isoquinoline system 1 by Bischler-Napieralski cyclization of an appropriate 6-phenethyl-6-azabicyclo[3.2.1]octan-7-one derivative 2 is described. Lactam 2 was prepared by three alternative procedures: (a) direct alkylation of normorphan 6 , (b) alkylation of lactim ether 7 with 3,4,5-trimethoxyphenacyl bromide followed by NaBH 4 reduction and hydrogenolysis, and (c) lactamization of amino esters 11 or 13 , which were obtained from ethyl or methyl 3-aminocyclohexanecarboxylate by direct alkylation or by acylation with 3,4,5-trimethoxyphenylacetyl chloride and further diborane reduction, respectively.

Synthesis and adrenergic properties of cyclic analogues of methoxamine: 2-amino-1-arylcyclohexanols and 2-amino-1,2,3,4-tetrahydro-1-naphthalenols

Abstract The synthesis, conformational study, α-stimulant, and β-blocking activities of cis- and trans-2-amino-1-arylcyclohexanols 4–7 and cis- and trans-2-amino-1,2,3,4-tetrahydro-1-naphthalenols 8–11 are described. These compounds can be considered as conformationally restrained analogues of methoxamine, isopropylmethoxamine, and their demethoxylated derivatives. 1H NMR data indicate that, in the 2-amino-1-arylcyclohexanol series, Ar and NHR groups hold a gauche relationship, which could account for their lack of α-agonist and β-blocking properties. Among the 2-aminonaphthalenols, only cis- and trans-10 showed α-agonist activities, although lower than that of methoxamine. These compounds were completely devoid of β-blocking properties. These results can be correlated with the conformation in solution found by 1H NMR for the above aminotetralols.

BENZOMORPHAN RELATED COMPOUNDS. XVII. OXIDATIVE CYCLIZATION OF N-ARYLETHYL-6,7-BENZOMORPHANS

The synthesis of two new bridged polycyclic systems (I and II), possessing a rigid N-arylethylbenzomorphan structure, by mercuric acetate cyclization of the corresponding seco derivatives (IV and VI, respectively) is described. The relative configuration of these compounds and the preferred indolo[2, 3-a]- or benzo[a]quin-olizidine conformation is assigned.