Digoxin dialdehyde reductive aminations. Structure proof of the perhydro-1,4-oxazepine product.
Digoxin dialdehyde reportedly undergoes reductive amination with primary amines to form a perhydro-1,4-oxazepine; however, no structural proof has been published to substantiate this belief. A digoxin perhydro-1,4-oxazepine derivative has been isolated from the reductive amination of digoxin dialdehyde and its structure determined by mass spectroscopy and NMR measurements. Comparison of the NMR, mass spectroscopy, and HPLC of two compounds obtained from the degradation of the digoxin reductive amination product with synthesized perhydro-1,4-oxazepine diastereomers showed them to be identical. We conclude that, under appropriate conditions, reductive amination products can be obtained, but caution that other products may be produced as well, especially under the conditions of bioconjugation to proteins.
Adamczyk
M
M
Department of Chemistry D9NM, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Grote
J
J
Mattingly
P G
PG
D000588:Amines / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D015394:Molecular Structure; D010077:Oxazepines / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
D000588:Amines; D010077:Oxazepines; C098160:digoxin 2-methyl-4-(4-nitrobenzyl)perhydro-1,4-oxazepine; C098159:digoxin dialdehyde; D004077:Digoxin