Details

Autor(en) / Beteiligte

• Romero, Arthur G
• Darlington, William H
• McMillan, Moses W

Titel

Synthesis of the Selective D2 Receptor Agonist PNU-95666E from d-Phenylalanine Using a Sequential Oxidative Cyclization Strategy

Ist Teil von

• Journal of organic chemistry, 1997-09, Vol.62 (19), p.6582-6587

Ort / Verlag

American Chemical Society

Erscheinungsjahr

1997

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Compound 1 (PNU-95666E) is a selective and high-affinity agonist at the dopamine D2 receptor subtype and is of interest as a potential agent for the treatment of Parkinson's disease. Requiring a synthetic route amenable to scale-up, a synthesis of this enantiomerically pure tricyclic compound was developed, starting from d-phenylalanine. Critical to the success of this synthesis were two oxidative nitrogen annulations to provide the tricyclic ring system. A highly efficient reduction with borane−methyl sulfide was used to reduce three different functional groups, a total of six hydrides transferred, with no concomitant racemization, contributing to the synthesis of 1 in eight steps with an overall yield of 26%. The utility of this synthetic route has been demonstrated by the completion this synthesis on multikilogram scale.