Endogenous natriuretic factors 6: the stereochemistry of a natriuretic gamma-tocopherol metabolite LLU-alpha.
2,7,8-Trimethyl-(S)-2-(beta-carboxyethyl)-6-hydroxy chroman (S-LLU-alpha) isolated from human uremic urine is apparently an oxidative side-chain degradation product of gamma-tocopherol. This compound exhibits natriuretic activity in vivo and it appears to mediate the inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the nephron. The stereochemistry at the C-2 of LLU-alpha has been unequivocally established to be S(+) by X-ray crystallographic analysis of a diastereomeric amide derivative. It was also established that the chroman ring oxidation of S-LLU-alpha proceeded without racemization at C-2. This finding can be extended to nonepimerization at C-2 of alpha-delta tocopherols (Vitamin E) during side-chain oxidation and stereospecificity (retention or inversion) of oxidative opening of the chroman ring. The resolution of the enantiomers of the parent compound and derivatives was accomplished by chiral high-performance liquid chromatography. The stereospecific enzymatic hydrolysis by an array of commercially available enzymes of the racemic methyl ester of LLU-alpha was investigated. The lipase from Humicola languinosa appears to be the best enzyme for resolution by selective hydrolysis of the racemic methyl ester.
Kantoci
D
D
Laboratory of Chemical Endocrinology, Loma Linda University School of Medicine, California 92350, USA.
Wechter
W J
WJ
Murray
E D
ED
Dewind
S A
SA
Borchardt
D
D
Khan
S I
SI
D002839:Chromans / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009318:Natriuresis / Q000502:physiology*; D011422:Propionates / Q000737:chemistry* / Q000378:metabolism; D013057:Spectrum Analysis; D013237:Stereoisomerism; D014810:Vitamin E / Q000737:chemistry* / Q000378:metabolism
D002839:Chromans; D011422:Propionates; D014810:Vitamin E; C107690:2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman