Synthesis of a potential bifunctional mimic of transaminases.
As a potential bifunctional mimic of transaminases 3,7-dimethyl-10-[3-(4- aminomethyl-5-hydroxy-6-methyl-3-pyridyl)propyl]-3,7,10- triazatricyclo[3.3.3.0(1,5)] undecane (I) has been synthesized by attaching 3,7-dimethyl-3,7,10-triazatricyclo [3.3.3.0(1,5)]undecane (II) to a pyridoxamine nucleus via an all-carbon chain. The chain length between the pyridine ring and II is restricted to three atom units so that the possibility for II to act bifunctionally during the transamination is maximized. In its protonated form, the nitrogen closest to the pyridine ring cannot deliver the proton intramolecularly to the alpha-carbon of the developing amino acid. To make the synthetic route generally applicable, introduction of the side-arm base is arranged at a later stage of the synthesis so that different di- or poly-amines can easily be used in place of II to prepare other target molecules that might possess bifunctional catalytic activity. This arrangement also greatly reduces the polarity and water-solubility of the intermediates and the purification of these compounds thus becomes much easier. The method of introducing the amino functionality at the C-4 methylene group described herein provides an alternative to that currently in use (reduction of oximes).
Wu
Y K
YK
Department of Organic Chemistry, University of Göteborg, Sweden.
Ahlberg
P
P
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D000637:Transaminases / Q000737:chemistry*
D001372:Aza Compounds; D003432:Cross-Linking Reagents; D011725:Pyridines; C074964:3,7-dimethyl-10-(3-(4-aminomethyl-5-hydroxy-6-methyl-3-pyridyl)propyl)-3,7,10-triazatricyclo(3.3.3.0(1,5))undecane; D000637:Transaminases