From methylglyoxal to new immunopotentiating ascorbic acid derivatives.
In Szent-Györgyi's search for alpha-dicarbonyl compounds that play an important role in cell regulation, 3-desoxyglucosulose was isolated first from liver but did not prove active. Methylglyoxal came next, however, its toxicity prompted Szent-Györgyi to suggest a combination with ascorbic acid which, indeed led to immunopotentiating enediol acetals although of low stability. Therefore the vinylogue of methylglyoxal, acetylacrolein was coupled with L-ascorbic acid carbanion. This second new reaction, of the aldol-type, led to the stable, potent immunoactive compound, 2-(5-methylfuryl)-3-ketogulonolactone cyclohemiketal that forms a completely surprising H-bond with succinic anhydride and succinimide based on an X-ray study. A third new reaction in which ascorbic acid plays the role of a Michael donor to alpha,beta-unsaturated aldehydes and ketones proved now to be of general validity; it is unexpectedly acid catalyzed and the adducts formed with aliphatic and alicyclic olefin ketones have definite immunopotentiating effect. A brief description of the biological effects of all types of new compounds is outlined.
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis*; D000447:Aldehydes; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011765:Pyruvaldehyde; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000447:Aldehydes; D007202:Indicators and Reagents; D011765:Pyruvaldehyde; D001205:Ascorbic Acid