Cleavage of some annulated tetrahydropyridines under the action of dimethyl acetylene dicarboxylate in protic solvents. New practical route to substituted pyrroles and indoles

Tetrahydropyrrolo[3,2-c]pyridines and tetrahydropyrido[4,3-b]indoles undergo piperidine ring opening under the action of dimethyl acetylene dicarboxylate in alcohols or in aqueous dioxane, providing beta-(alk)oxy-substituted pyrroles (indoles) in moderate to high yields.     

Reaction of 3,3-dimethyl- and 3-spirocyclohexyl-tetrahydroisoquinolines with alkynes*

It has been found that 2,3,3-trimethyl-1-phenyl- and 1,2-dimethyl-3-spirocyclohexyltetrahydro-isoquinolines react with activated alkynes in methanol with cleavage of the tetrahydropyridine ring to give methoxybenzyl- and methoxyethylbenzenes, and in boiling acetonitrile form N-butenoyl derivatives from N-methylspirocylohexyltetrahydroisoquinoline by its reaction with acetylacetylene.     

Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity

Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, 3e (R³ = CH₂OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (K_i = 4.9 μM), equipotent with the corresponding 6-phenyl derivative 3n (R³ = Ph, K_i = 4.5 μM), but 90-fold more water-soluble.     

New approaches to the synthesis of benzo[h]pyrroloisoquinoline derivatives

An effective strategy for the synthesis of benzo[h]pyrrolo[2,1-a]isoquinoline derivatives has been developed. The process can be described as a one-pot domino reaction that consists of an initial Michael addition, intramolecular cyclization, and subsequent transformations leading to the formation of the desired products. A wide range of structurally diverse hydrogenated benzo[h]pyrrolo[2,1-a]isoquinolines were obtained in 34–98% yield. This strategy represents an efficient catalyst-free procedure that allows the synthesis of previously inaccessible compounds.