SYNTHESIS OF RING-LABELED l-THYROXINE-C$sup 1$$sup 4$
Although I/sup 131/-labeled and carboxyl C/sup 14/-labeled thyroxine have been used to study the metabolism of thyroid hormone, these labels are readily removed physiologically, and knowledge about the metabolic fate of the diphenyl ether moiety of the molecule is incomplete. Preliminary investigation of this aspect of thyroxine metabolism, L -thyroxine labeled with C/sup 14/ in the phenolic ring was synthesized. To utilize a previous method for the convenient preparation of L-thyroxine from p-methoxyphenol, it was necessary to prepare this intermediate from phenol-C/sup 14/ by the reaction scheme which is shown. Then, by modification of the Chalmers method for the condensation of N- acetyl-3,5-dinitroL-tyrosin; ethyl ester with p-methoxyphenol and conversion of the condensation product to L-thyroxine, it was possible to prepare L-thyroxine-C/ sup 14/ in 12 steps in an over-all yield of 2.6%. The detailed procedure is described. The starting material, uniformly labeled C/sup 14/-phenol (specific activity 1.3 mC/mmole, 2.3 mmoles or 216 mg) was converted to phenyl-C/sup 14/- benzenesulfonate by addition of benzensefulfonyl chloride in pyridine. The product was converted to the pnitrophenyl derivative (with KNO/sub 3/ and concentrated H/sub 2/SO/sub 4/ which was converted by alkali to p-nitrophenol-C/ sup 14/. This was treated with diazomethane to form p-nitroanisole-C/sup 14/ which was reduced with Pt and H/sub 2/ to p-aminoanisole-C/sup 14/. By diazotization p-methoxyphenol-C/sup 14/ was prepared, which was converted to L- thyroxine-C/sup 14/ by the Chalmers procedure. Characterization of the labeled hormone by paper chromatography and assay of its endocrine potency are described. The L-thyroxine-C/sup 14/ exhibited biological activity equivalent to authentic L -thyroxine when tested by the inhibition of propylthiouracil-induced goiters in rats and the suppression of thyroidal I/sup 131/ uptake. (BBB)
- Research Organization:
- Univ. of Utah, Salt Lake City
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-18-016074
- OSTI ID:
- 4077215
- Journal Information:
- Journal of Medicinal Chemistry (U.S.), Journal Name: Journal of Medicinal Chemistry (U.S.) Vol. Vol: 6; ISSN JMCMA
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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Related Subjects
ANTIFERROMAGNETISM
CARBON 14
CHEMICAL REACTIONS
CHEMISTRY
COOLING
COPPER
ESTERS
EXPANSION
FERROMAGNETISM
HEATING
HORMONES
IODINE 131
LABELLED COMPOUNDS
LIQUEFYING
MAGNETIC MATERIALS
MAGNETISM
MEASURED VALUES
METABOLISM
METALS
PHENOLS
PLUTONIUM
PREPARATION
PYRIDINES
REACTION KINETICS
SULFONIC ACIDS
TEMPERATURE
THYROID
THYROXINE