Synthesis and antiaggregant and hypotensive activity of benzo-annelated azabicyclo[m.n.0]alkanes

Abstract

Three-component condensation of veratrole, isobutylene oxide, and aliphatic w-chloronitriles via the Ritter reaction leads to 1-(w-chloroalkyl)-6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolines, the reduction of which with NaBH 4 yields benzoannelated azabicyclo[m.n.0]alkanes. The synthesized compounds have been tested for hypotensive and antiaggregant activity.

Small Heterocycles in Multicomponent Reactions

“…A multicomponent Ritter-type reaction has been applied to make substituted dihydroisoquinolines ( 82 ). The 3CR of 77 , isobutylene oxide ( 78 ), and a nitrile ( 80 ) was performed in a mixture of toluene and concentrated H 2 SO 4 to promote formation of intermediate 81 through an S N 1 mechanism (Scheme ) . After reduction with sodium borohydride, tetrahydroisoquinolines could be accessed.…”

Chemoselective Strategy for the Direct Formation of Tetrahydro-2,5-methanobenzo[c]azepines or Azetotetrahydroisoquinolines via Regio- and Stereoselective Reactions

“…Only a few approaches for the synthesis of these azetidine- and pyrrolidine-fused tetrahydroisoquinolines have been developed. ,,,, Azeto­[2,1- a ]­isoquinolines 1 have been prepared by a multitude of routes, such as (1) via the related isoquinolines by intramolecular ring closure, (2) via hydride reduction of the β-lactam into azetidine, (3) using [2 + 2]-cycloaddition …”

“…22 Only a few approaches for the synthesis of these azetidine 23 and pyrrolidine-fused tetrahydroisoquinolines have been developed. 4,6,8,24,25 Azeto[2,1-a]isoquinolines 1 have been prepared by a multitude of routes, such as (1) via the related isoquinolines by intramolecular ring closure, (2) via hydride reduction of the β-lactam into azetidine, 7 (3) using [2 + 2]cycloaddition. 26 The construction of the 2,5-methanotetrahydro-2H-2benzazepine skeleton (2) has been achieved through only three main strategies: 27 Pictet−Spengler reaction 11,28−31 or a ring closure of the pyrrolidine derivative, 10,32 an intramolecular [3 + 2]-cycloaddition, 13,14 and via intramolecular Nalkylation.…”