RESUMEN
Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pairs of dopaminergic 1-BTHIQs enantiomers through a classical methodology in asymmetric synthesis. The (1S)-enantiomers (14a-16a) bind to D1 and D2 dopamine receptors with affinities 5-15 times higher than those of the corresponding (1R)-enantiomers (14b-16b). Moreover, (1S)-14a inhibits [3H]dopamine uptake with high affinity. It appears that synthesis and testing of (S)-enantiomers of BTHIQ are very important for the search for new active drugs at dopamine receptors.
Asunto(s)
Compuestos de Bencilo/síntesis química , Antagonistas de Dopamina/síntesis química , Isoquinolinas/síntesis química , Animales , Benzazepinas/metabolismo , Compuestos de Bencilo/química , Compuestos de Bencilo/metabolismo , Unión Competitiva , Cuerpo Estriado/metabolismo , Cuerpo Estriado/ultraestructura , Cristalografía por Rayos X , Dopamina/metabolismo , Antagonistas de Dopamina/química , Antagonistas de Dopamina/metabolismo , Técnicas In Vitro , Isoquinolinas/química , Isoquinolinas/metabolismo , Ligandos , Masculino , Racloprida/metabolismo , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Estereoisomerismo , Relación Estructura-Actividad , Sinaptosomas/metabolismoRESUMEN
Ketimino(phosphino)gold(I) complexes of the type [Au[NR=C(Me)R']L]X (X = ClO4, R = H, L = PPh3, R'=Me (la), Et (2a); L=PAr3 (Ar=C6H4OMe-4), R'=Me (1b), Et (2b); L=PPh3, R=R'=Me (3); X= CF3SO3 (OTf), L=PPh3, R=R'=Me (3'); R=Ar, R'=Me (4)) have been prepared from [Au(acac)L] (acac = acetyl acetonate) and ammonium salts [RNH3]X dissolved in the appropriate ketone MeC(O)R'. Complexes [Au(NH=CMe2)2]X (X = C1O4 (6), OTf (6')) were obtained from solutions of [Au(NH3)2]X in acetone. The reaction of 6 with PPN[AuCl2] or with PhICl2 gave [AuCl(NH=CMe2)] (7) or [AuCI2(NH=CMe2)2]ClO4 (8), respectively. Complex 7 was oxidized with PhICl2 to give [AuCl3(NH=CMe2)] (9). The reaction of [AuCl(tht)] (tht = tetrahydrothiophene), NaClO4, and ammonia in acetone gave [Au(acetonine)2]ClO4 (10) (acetonine = 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine) which reacted with PPh3 or with PPN[AuCl2] to give [Au(PPh3)(acetonine)]ClO4 (11) or [AuCl(acetonine)] (12), respectively. Complex 11 reacts with [Au(PPh3)(Me2CO)]ClO4 to give [(AuPPh3)2(mu-acetonine)](ClO4)2 (13). The reaction of AgClO4 with acetonine gave [Ag(acetonine)(OClO3)] (14). The crystal structures of [Au(NH2Ar)(PPh3)]OTf (5), 6' and 10 have been determined.
RESUMEN
In the title compound, C(14)H(15)ClF(2)N(2)O, the Z configuration has been confirmed. The molecular structure shows an intramolecular N-H.N hydrogen bond [H.N 2.04 (6), N.N 2.709 (6) A and N-H.N 124 (5) degrees ]. This interaction could be responsible for the Z configuration.
RESUMEN
The reactivity of the tetranuclear metallated palladium compound (Pd[mu 2-(C6H4)PPh2]Br)4 (1) with different ligands has been investigated with the aim of evaluating the influence of the entering ligand on the nature of the reaction products. The results confirmed the ability of the ligand [(C6H4)PPh2]- to expand a bridging [mu 2-] or a chelating [eta 2-] coordination mode, depending on the auxiliary ligands present in the complex. Bulky phosphines stabilize mononuclear species of formula (Pd[eta 2-(C6H4)PPh2]Br[P]), with a four-atom metallocycle, while small phosphines give dinuclear compounds. The molecular structures of three different metalated palladium compounds have been determined by single-crystal X-ray crystallography; the tetranuclear (Pd[mu 2-(C6H4)PPh2]Cl)4 (2), the dinuclear(Pd[mu 2-(C6H4)PPh2]Br[PMe3])2 (3), and the mononuclear (Pd[eta 2-(C6H4)PPh2]Br[PCBr]), (PCBr = P(o-BrC6H4)Ph2) (9) were obtained, the first one by halogen exchange reaction and the others by frame degradation of 1.