Stereospecific synthesis of 16. cap alpha. -hydroxy-17-oxo steroids by controlled alkaline hydrolysis of corresponding 16-bromo 17-ketones and its reaction mechanism

Journal Article · Fri Oct 08 04:00:00 EDT 1982 · J. Org. Chem.; (United States)

DOI:https://doi.org/10.1021/jo00142a004· OSTI ID:6431736

Numazawa, M ^[1]; Nagaoka, M; Osawa, Y

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1. Tohoku Coll. of Pharmacy, Sendai, Japan

Synthesis of 16..cap alpha..-hydroxy-17-oxo steroids and 3..beta..,16..cap alpha..-dihydroxy-5-17-oxoandrosten-3-yl sulfate from 16..cap alpha..-bromo-17-oxo steroids and the reaction mechanism of the controlled alkaline hydrolysis are described. Treatment of the bromo ketones with NaOH in aqueous DMF gave the 16..cap alpha..-hydroxy 17-ketones stereoselectively in 95% yield without formation of other ketols. The sodium salt of 3-sulfate was also obtained in one step in 85% yield from the corresponding bromo ketone. Isotope-labeling experiments and time-course studies showed that equilibration between the 15-bromo epimers occurs by the reaction mechanism described in this report. The 16..beta..-morpholino derivaive obtained by reaction with morpholine was shown to be an isomerized product of the 16..cap alpha.. isomer which is produced also by S/sub N/2 displacement of the 16..beta..-bromine. The mechanism of ketol rearrangement to the 17..beta..-hydroxy-16-oxo compound was found to involve a hydration to the carbonyl function. The new hydration dehydration mechanism is proposed for the ketol rearrangement.

• OSTI ID: 6431736
• Journal Information: J. Org. Chem.; (United States), Journal Name: J. Org. Chem.; (United States) Vol. 47:21; ISSN JOCEA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400302* -- Organic Chemistry-- Isotope Effects-- (-1987)
CHEMICAL PREPARATION
CHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
DECOMPOSITION
EVEN-EVEN NUCLEI
HYDROLYSIS
HYDROXY COMPOUNDS
ISOTOPE EFFECTS
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
LYSIS
MASS SPECTROSCOPY
NUCLEI
ORGANIC COMPOUNDS
OXYGEN 18
OXYGEN ISOTOPES
REACTION KINETICS
SOLVOLYSIS
SPECTROSCOPY
STABLE ISOTOPES
STEROIDS
SYNTHESIS