SYNTHESIS AND OPTICAL RESOLUTION OF (R)- AND (S)-TRANS-7-HYDROXY-2-[N-PROPYL-N-(3'-IODO-2'-PROPENYL)AMINO]TETRALIN - A NEW D3 DOPAMINE-RECEPTOR LIGAND

An improved method for synthesis and resolution of (R,S)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino] tetralin (trans-7-OH-PlPAT, 5), a new D3 dopamine receptor ligand, was reported. Both isomers, (R)-(+)- and (S)-(-)-5, were prepared and characterized. HPLC retention times obtained on a chiral column for these isomers were consistent with those observed for [I-125]-(R)-(+)- and (S)-(-)-5. Direct radioiodination of an optically resolved tin precursor, (R)-(+)-7, yielded the desired [I-125](R)-(+)-5, which is a simpler method for synthesis of this ligand. Binding studies with membrane preparations containing D3 dopamine receptors expressed in Spodoptera frugiperda (Sf9) cells also suggested that the [I-125](R)-(+)-5 is the active isomer (K-d = 0.05 nM). The schemes described may provide an efficient way for synthesizing a large quantity of this new D3 dopamine receptor ligand for in vivo behavior studies.