Synthesis and pharmacological properties of certain derivatives of octahydroacridines

Synthesis, crystal structure, Hirshfeld surface analysis and energy framework calculations of trans-3,7,9,9-tetramethyl-10-(prop-2-yn-1-yl)-1,2,3,4,4a,9,9a,10-octahydroacridine

“…The octahydroacridine (OHA) scaffold is a synthetic nitrogen heterocycle of significant importance in the fields of organic and medicinal chemistry. Its biological and pharmacological potential applications have been demonstrated over past decades (Ermolaeva et al, 1968;Del Giudice et al, 1997;Ulus et al, 2016). The assembly of the OHA motif has been achieved by synthetic routes involving classic Beckman rearrangement (Sakane et al, 1983), intramolecular Friedel-Crafts acid-mediated cyclization (Kouznetsov et al, 2000) and multicomponent aminocyclization reactions (Selvaraj & Assiri, 2019).…”

Highly Diastereoselective Synthesis of New trans-Fused Octahydro­acridines via Intramolecular Cationic Imino Diels–Alder Reaction of N-Protected Anilines and Citronellal or Citronella Essential Oil

“…Octahydroacridines (OHA) are important tricyclic Nheterocycles reported to possess a wide range of biological activities. Some pharmacological properties, such as antidepressant, 1 inhibitory of gastric acid secretions, 2 and possible prevention of Alzheimer-type senile dementia, 3 have been attributed to this scaffold. The preparation of these heterocycles has been carried out employing different synthetic approaches such as Beckman rearrangement, 4 Friedel-Crafts cyclization, 5 and more recently, the powerful and versatile acid-catalyzed imino Diels-Alder reaction.…”

Bismuth(III) Chloride: An Efficient Catalyst for the One-Pot Stereoselective Synthesis of Octahydroacridines

“…Octahydroacridine derivatives are an important class of compounds with interesting pharmacological activity. [2][3][4] Therefore, many synthetic methods have been reported for the preparation of the octahydroacridine skeleton, such as catalytic hydrogenation of acridines, 5 amino-claisen rearrangement of geranyl aniline, 6 Beckman rearrangement of oxime sulfonates, 7 and acid-catalyzed condensation of aniline with isophorone. 8 The intramolecular hetero-Diels-Alder reaction of N-arylimines with nonactivated olefins tethered to the diene system is the most powerful synthetic tool for constructing nitrogen heterocyclic compounds.…”

“…The cyclization was carried out by the addition of BiCl 3 (5 mol%) to a cooled solution of citronellal (2) and aniline (1a) in acetonitrile, which resulted in the formation of octahydroacridine 3a exclusively as a single product in high yield. The reaction was instantaneous as followed by TLC, and found to be highly diastereoselective.…”