A series of beta-substituted and beta,beta-disubstituted N-acyl 5-methoxy-1-methyltryptamines and 5-methoxytryptamines have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human MT(1) and MT(2) receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency of all analogues was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. beta-Methylmelatonin (17a) and beta,beta-dimethylmelatonin (17b), though showing a slight decrease in binding at human receptors, show an increase in potency on Xenopus. N-Butanoyl 5-methoxy-1-methyl-beta,beta-trimethylenetryptamine (12c) is an antagonist at human MT(1) receptors but an agonist at MT(2), while N-butanoyl 5-methoxy-1-methyl-beta,beta-tetramethylenetryptamine (13c) is an antagonist at MT(1) but had no action at MT(2) and is one of the first examples of an MT(1) selective antagonist.

The combination of three reagents—a tridentate pybox ligand (pybox=pyridine bis(oxazoline)), magnesium perchlorate, and Hünig base (iPr2EtN)—allows the catalytic generation of a chiral glycine enolate from 1 that undergoes highly enantioselective addition to a range of aryl aldehydes 2. The protected aryl β‐hydroxy‐α‐amino acid products obtained include a protected version of one of the aryl serine units present in the glycopeptide antibiotic vancomycin.

Aller guten Dinge sind drei Reagentien: Ein katalytisches System aus einem dreizähnigen Pybox‐Liganden (Pybox=Bis(oxazolinyl)pyridin), Magnesiumperchlorat und der Hünig‐Base (iPr2EtN) erzeugt das chirale Glycinenolat von 1, das hoch enantioselektiv an Arencarbaldehyde 2 addiert. Unter den so erhältlichen geschützten Aryl‐β‐hydroxy‐α‐aminosäuren ist auch eine geschützte Version einer der Arylserin‐Einheiten des antibiotischen Glycopeptids Vancomycin.

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