T. N. Borisova

The first synthesis and X-ray crystal structure of tetrahydropyrrolo[2,3-d]azocines

Tetrahydropyrrolo[3,2-c]pyridines (THPP) upon the reaction with DMAD in acetonitrile or DMSO at rt underwent ring expansion, affording tetrahydropyrrolo[2,3-d]azocines; these latter compounds have not previously been reported in the literature. The crystal structure and conformation of these derivatives was established by X-ray crystallography.

Chapter 2 Synthesis of Heteroannulated Azocine Derivatives

Publisher Summary This chapter reviews that azocinoindoles have been investigated extensively due to the host of alkaloids with an azocinoindole fragment in their structure. The existence of six isomeric azocinoindoles, in which an azocine ring is annulated with a pyrrole fragment, is possible. This chapter explores that the first method for the preparation of tetrahydroazocino indoles was reported in 1966. In the succeeding years, this reaction came to be known as the witkop photocyclization. The main reasons for investigating the reactivity of azocinoindoles is connected with the synthesis of pentacyclic indole alkaloids of the Strychnos group. A different approach to the derivation of Strychnos-type pentacyclic alkaloids has been used. Photocyclization of N-chloroacetyl derivative 99 takes place in position 4 of the indole core to form 100.

TANDEM MICHAEL ADDITION - HOFFMAN ELIMINATION SEQUENCE OF DMAD ON TETRAHYDROPYRROLO[3,2-C]PYRIDINES. NEW ROUTE TO VINYLPYRROLES .

The reaction of tetrahydropyrrolo[3,2-c]pyridines with DMAD in THF at room temperature results in piperidine ring cleavage producing aor ß-vinylpyrroles in moderate to good yields. The resulting compounds are haidly available by other synthetic means and are good candidates for further transformations . Introduction. There are two well-known procedures for piperidine ring cleavage: Hofmann (1) and von Braun (2) reactions . The scope of these reactions is limited and they are most frequently used to determine substituents position in piperidine moiety of natural and synthetic compounds. Recently we have reported piperidine ring cleavage in 1etrahydropyrrolo[3,2-c]pyridines under the action of acetic anhydride at 70° C resulting with the formation of 2-(amethyl-ß-acetamidoethyl)-3-vinylpyrroles in moderate yields, while the target 2-acetyl substituted pyrroles have not been isolated (3). In continuation of our studies of pyrrolo[3,2-c]piperidines reactivity and biologic activity investigation (4), we have carried out the reaction of 2-trifluoroacetylsubstituted derivative 1 with DMAD under reflux in THF in the presence of triphenyl phosphine . Results and Discussion. According to the literature data (5) we expected the formation of a corresponding trifluoromethyl substituted lactone that could exhibit very interesting biologic properties. Scheme 1 Et / Et— DMAD CF3 THF.r.t. CF3 1 2 62 % Ο

Heterocyclization of tropinone oximes and 3-methyl-3-azabicyclo[3.3.1.]-nonan-9-one with acetylene in a superbasic medium

Tropinone oxime reacts with acetylene in syperbasic medium to form ordinary products of heterocyclization. The oxime of 3-methyl-3-azabicyclo[3.3.1]nonan-9-one does not undergo heterocyclization due to the impossibility of a [3,3]-sigmatropic rearrangement of its vinyl ether.

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 β-(alk)oxy-substituted pyrroles (indoles) in moderate to high yields.

A novel multi-component approach to the synthesis of pyrrolo[2,1-a]isoquinoline derivatives

A route towards pyrrolo[2,1-a]isoquinolines through a 3CR of 1-aroyl dihydroisoquinolines, activated alkynes and alcohols has been developed.

Synthesis of 6-aryl-Substituted Azocino-[5,4-b]indoles from 1-aryl-Substituted 2-Ethyltetrahydro-β-Carbolines

We optimized the reaction of tetrahydropyridine ring expansion in 1-aryl-substituted tetrahydro-β-carbolines by the action of activated alkynes and achieved higher than 70% yields of the target indoloazocines. The substituents in the 1-aryl ring and at the indole nitrogen atom were shown to affect the rate and selectivity of this transformation.

Investigation on the antiplatelet activity of pyrrolo[3,2‐c]pyridine‐containing compounds

A series of 4,5,6,7‐tetrahydro‐1H‐pyrrolo[3,2‐c]pyridines (THPPs), mostly C(2)‐substituted derivatives, and some 2, 3, 4, 5‐tetrahydro‐1H‐pyrido[4, 3‐b]indoles (THPIs) were synthesized and tested in‐vitro for their ability to inhibit aggregation of human platelet‐rich plasma (PRP) induced by adenosine 5′‐diphosphate (ADP) and adrenaline (epinephrine). 5‐Benzyl THPP (3), 2‐(benzylamino)methyl THPP (5f) and 2‐ethyl THPI (6) moderately and dose‐dependently inhibited platelet aggregation induced by adrenaline and, to a lesser extent, by ADP. These compounds inhibited the second phase of the PRP aggregation triggered by adrenaline, which largely depends upon thromboxane A2 production and ADP release. In the adrenaline‐stimulated aggregation, the THPI derivative 6 was found to be nearly equipotent with aspirin, their IC50 values (concentration effecting 50% inhibition of aggregation) being 90 and 60 μM, respectively. A relation between activity and calculated octanol‐water partition coefficient suggested that a log P value around 2.5 should be the optimal lipophilicity value for the activity of THPP‐containing compounds.

Transformations of tetrahydro-1,4-benzoxazepines and tetrahydro-1,4-benzothiazepines under the action of alkynes. First example of the synthesis of tetrahydro-1,4-benzothiazonine-6-carboxylate

It was shown that 2,3,4,5-tetrahydro-1,4-benzoxazepines were cleaved at the N–C(5) bond under the action of activated alkynes in methanol, forming o-(methoxyethyl)- and o-(methoxybenzyl)-phenyl(aminoethyl) ethers. The cleavage rate depended on the electronic effects of the substituents at the C-5 atom. Thiazepine ring expansion in tetrahydro-1,4-benzothiazepine was achieved for the first time via reaction with methyl propiolate to give a benzothiazonine.

Synthesis of pyrrolo[1,2-a][1,6]benzodiazonines from pyrrolo[1,2-a][1,4]benzodiazepines and alkynes containing electron-acceptor substituents

It has been established that the reaction of pyrrolo[1,2-a][1,4]benzodiazepines with activated alkynes gives pyrrolo[1,2-a][1,6]benzodiazonines as the products of diazepine ring expansion. In the case of pyrrolo[1,2-a][1,4]benzodiazepine, substituted with formyl group at the pyrrole ring, both expansion and cleavage of the diazepine fragment can occur.