39798-12-4

Upstream product

• 58101-60-3 methyl cyclopent-3-ene-1-carboxylate 

Downstream Products

• 77661-92-8 (2S,3aR,19aS)-2-Benzyloxymethyl-tetradecahydro-4,7,10,13,16,19-hexaoxa-cyclopentacyclooctadecene 
• 77714-64-8 2-[(1R,2S,4S)-4-Benzyloxymethyl-2-(2-hydroxy-ethoxy)-cyclopentyloxy]-ethanol 
• 77714-62-6 (3aR,5S,6aS)-5-Benzyloxymethyl-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxole 
• 77714-63-7 4-(benzyloxymethyl)cyclopentane-cis-1,2-diol 

Relevant academic research and scientific papers

Diastereoselective synthesis of conformationally restricted KOR agonists

In order to analyze the bioactive conformation of flexible KOR agonists the ethylenediamine KOR pharmacophore was conformationally constrained by incorporation into a bicyclic system. For this purpose, 2-azabicyclo[3.2.1.]octan-7-amines were designed, synthesized and pharmacologically evaluated. The primary amine 14 as first key intermediate was prepared in a six-step synthesis starting with methyl cyclopent-3-enecarboxylate 9. Whereas phenylacetamides failed to provide bicyclic compounds, the intramolecular nucleophilic substitution of the sulfonamide 25 was initiated by deprotonation with NaH affording the bicyclic compound 26 in 72% yield. The three-step introduction of the pharmacophoric pyrrolidine ring started with nucleophilic substitution of exo-configured tosylate 26 with NaN3, which unexpectedly occurred under retention of configuration leading to exo-configured azide 31. The final KOR agonists 35 and 36 with exo-configured amino moieties were obtained by removal of the N-tosyl moiety of 33 and introduction of the second pharmacophoric element by acylation with dihalophenylacetyl chlorides. The KOR affinity of the pyrrolidine 35a is in the high nanomolar range (Ki = 862 nM). The low KOR affinity is explained by a non-appropriate dihedral angle of 137°/141° of the N(pyrrolidine)-C-C-N(acyl) system. As observed for stereoisomers of potent KOR agonists, phenylacetamide 35a and more importantly sulfonamides 33a and 33b show moderate affinity at σ1 receptors (Ki = 109-208 nM). This journal is

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