Absolute Stereochemical Assignment of SCH 71450, a Selective Dopamine D₄ Receptor Antagonist, Through Enantioselective Epimer Synthesis

Abstract

The absolute stereochemical assignment of SCH 71450, a selective dopamine D4 receptor antagonist, has been successfully confirmed through enantioselective epimer synthesis. An allyl substituent on the p‐hydroxybenzyl group was demonstrated to be an appropriate protecting group for Noyori Ru‐catalyzed asymmetric transfer hydrogenation of the imine derivative. The construction of the sugar moiety involved a β‐glycosylation reaction assisted by neighboring group participation. By comparison with literature data, the absolute stereochemistry at the C‐1 carbon on the tetrahydroisoquinoline core has been assigned the S configuration.

Higenamine 4′-O-β-d-glucoside in the lotus plumule induces glucose uptake of L6 cells through β2-adrenergic receptor

“…After a glycosylation reaction of 3 with glucosyl imidate in the presence of boron trifluoride, the obtained 4 was deprotected and the desired diastereomer 1 was selectively purified using HPLC (see Scheme 1). The 1 H NMR spectra of synthetic 1 matched the reported data, 10 and the data of isolated 1. The specific rotation of the synthetic 1 ([a] D 25 À20.0) also matched with the isolate ([a] D 25 À17.8) thus confirming the structure.…”

“…13,14 The stereochemistry of the higenamine moiety of the current isolated compound was easily determined as S-enantiomer by comparison with reported NMR data. 10 …”

“…6 and 7 were combined and separated thrice using high performance liquid chromatography (HPLC) [(1) Inertsil ODS-3 (GL Science Co., /20 Â 250 mm), gradient elution from 5% aq methanol to 50% aq methanol in 60 min; with reference values. 10,11 The data in Table 1 was obtained in D 2 O because it was easier to distinguish the signals. The specific rotation was [a] D 25 À17.8 (c = 0.8, MeOH).…”

Synthesis and Biological Evaluation of 3-Styrylchromone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors

“…34) Solid K 2 CO 3 (16.6 g, 120 mol) was added to a solution of 4-hydroxyphenylacetic acid (3h, 4.6 g, 30 mmol) and allylbromide (9.4 g, 75 mmol) in EtOH (150 mL) at room temperature, and the mixture was refluxed for 5 h. To the cooled slurry was added KOH (6.7 g, 120 mmol) and stirring was continued for 12 h. The solvent was removed, the residue taken up in H 2 O (500 mL), washed with Et 2 O (100 mL), acidified with conc. HCl and extracted with EtOAc.…”

“…mp 76-77°C (lit. 34) 3,4-Bis(2-propenyloxy) benzeneacetic Acid (3g): According to the procedure for the preparation of compound (3f), 3,4-dihydroxyphenylacetic acid (3i, 6.8 g, 50 mmol) and allylbromide (24.2 g, 200 mmol) were treated with K 2 CO 3 (41 g, 300 mol) followed by KOH (11.2 g, 200 mmol) to give the title compound (3g) in 92% yield. Colorless semisolid.…”