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Biomedical subjects

Y Osawa

Publications and source records attributed to Y Osawa.

At least 181 records · Page 10Linked to original sources
PubMed1981

Synthesis of 16 alpha-bromoacetoxy androgens and 17 beta-bromoacetylamino-4-androsten-3-one: potential affinity labels of human placental aromatase.

A novel synthesis of 16 alpha-hydroxy-4-androstene-3,17-dione (3), 16 alpha-hydroxy-4-androstene-3,6,17-trione (4), 17 beta-amino-5-androsten-3 beta-o1 (10) and 17 beta-amino-4-androsten-3-one (14) is described. 16 alpha-Bromoacetoxy-4-androstene-3,17-dione (5), 16 alpha-bromoacetoxy-4-androstene-3,6,17-trione (6) and 17 beta-bromoacetylamino-4-androsten-3-one (15) were synthesized as potentially selective irreversible inhibitors of androgen aromatases. 16 alpha-Bromo-4-androstene-3,17-dione (1) and 16 alpha-bromo-4-androstene-3,6,17-trione (2) were converted to compounds 3 and 4 in 80-90% yield by controlled stereospecific hydrolysis using sodium hydroxide in aqueous pyridine. Reductive amination of 3 beta-hydroxy-5-androsten-17-one and 3-methoxy-3,5-androstadien-17-one (11) using ammonium acetate and sodium cyanohydridoborate (NaBH3CN) and a subsequent treatment with acid gave the amines 10 and 14 respectively, as a salt. The corresponding 17-imino compounds 9 and 13 were also isolated from the reaction mixtures when methanol was used as a solvent for the reaction. The 16 alpha-hydroxyl compounds 3 and 4 and the 17 beta-amino compound 14 were converted to the corresponding bromoacetyl derivatives, 5, 6, and 15, with bromoacetic acid and N,N'-dicyclohexylcarbodiimide.

Affinity Labels↗
PubMed1980

Increased 17 beta-hydroxysteroid dehydrogenase activity in a masculinizing adrenal adenoma in a patient with isolated testosterone overproduction.

The patient studied had noted the onset of virilization shortly after menopause. Urinary 17-ketosteroid levels were normal, as were fractionated 17-ketosteroid levels by gas liquid chromatography, but for 3 yr, serum testosterone levels had been greater than 490 ng/dl. The ovaries were found to be normal by laparoscopy. Abdominal exploration revealed a 1-cm adenoma in the right adrenal. A part of the adenoma excised from our patient was homogenized and incubated with 5 microCi [14C]androstenedione. Five percent of the 14C was converted by the tumor homogenate to a metabolite with the same mobility as testosterone on LH-20 chromatography. After thin layer chromatography, the radiolabeled material together with 3H-labeled authentic testosterone were crystallized to a constant specific activity. The net rate of testosterone synthesis by the tumor was 26 pmol/mg wet tissue wt.h vs. 0.56 pmol/mg.h by a control adrenal homogenate. Thus, the tumor demonstrated a 50-fold increase in 17 beta-hydroxysteroid dehydrogenase activity compared to normal adrenal tissue. This is the first report to identify altered activity of a specific enzyme system in this syndrome of isolated adrenal testosterone overproduction.

17-Hydroxysteroid Dehydrogenases↗
PubMed1979

Synthesis and some reactions of 6-bromoandrogens: potential affinity ligand and inactivator of estrogen synthetase.

The synthesis of epimeric 6-bromo-4-androstene-3,17-dione (1a and 1b), 6-bromotestosterone (2a and 2b) and its acetate (3a and 3b), and 6-bromo-16 alpha-acetoxy-4-androstene-3,17-dione (5a and 5b), and 6 beta-bromo-16 alpha-hydroxy-4-androstene-3,17-dione (4) is described. The interconversions among compounds 1, 2, and 3 are also studied. The 6 beta-isomer (1b, 2b, and 3b) was epimerized to the 6 alpha-isomer (1a, 2a and 3a) in carbon tetrachloride or chloroform-methanol (9:1) and the 6 alpha-isomer was isolated by fractional crystallization from the epimeric mixture. 6 alpha-Bromo isomer 1a was also epimerized back to 6 beta-bromo isomer 1b in chloroform-methanol (9:1). Two polymorphic forms of 6 beta-bromotestosterone acetate (3b) were isolated (mp. 114--117 degrees and 138--141 degrees). The 6 beta-bromo isomers were found to be unstable in methanol and decomposed to give 5 alpha-androstane-3,6-dione derivative (6). The results of irreversible inactivation of human placental androgen aromatase with some of these 6-bromoandrogens are discussed.

Methods↗
PubMed1979

Elevation of visual pattern discrimination limen in monkeys with total removal of inferotemporal cortex.

Attempts were made to test the validity of the general view that inferotemporal lesions in monkeys do not result in a visual acuity disorder. It was found in the first experiment that monkeys with total removal of the inferotemporal visual area (TIT monkeys) showed a significant elevation of the discrimination limen for visual patterns of reduced sizes even when compared to monkeys with removal of lateral striate cortex (LS monkeys); yet in a food-morsel (raisin) detection test the TIT monkeys performed as well as normal monkeys, although the LS monkeys showed significant deficits. A second experiment was conducted, in which the same subjects were tested with the same patterns as in the first experiment but with the stimulus background changed from the square used earlier to an enlarged disc. While both normal and LS monkeys performed this task easily, the TIT monkeys could not learn the discrimination within the training limit of 1,200 trials. The results suggest that such a marked elevation of the discrimination limen in the TIT monkeys as found in the first experiment is not attributable to a visual acuity disorder, but is explained as due to an impairment of the pattern perception mechanism.

Animals↗
PubMed1978

Improved synthesis of 16alpha-hydroxylated androgens: intermediates of estriol formation in pregnancy.

16alpha-Hydroxyandrostenedione (16alpha-hydroxyandrost-4-ene-3,17-dione), 16alpha-hydroxytestosterone (16alpha,17beta-dihydroxyandrost-4-en-3-one) and 16alpha-hydroxydehydroepiandrosterone 3-sulfate (3beta, 16alpha-dihydroxyandrost-5-en-17-one 3-monosulfate) were synthesized by a new chemical approach with much improved yield. 16alpha-Bromoandrostendione was converted to the hydrazone of 16alpha-hydroxyandrostenedione which gave 16alpha-hydroxyandrostenedione on acid hydrolysis in total 63% yield. Oxidation of 16alpha-hydroxydehydroepiandrosterone with Jones' reagent also selectively afforded 16alpha-hydroxyandrostenedione. 16alpha-Hydroxytestosterone was observed by selective reduction of 16alpha-hydroxyandrostenedione with sodium borohydride. Reaction of 16alpha-hydroxydehydroepiandrosterone with chlorosulfonic acid in pyridine selectively gave the 3-monosulfate. The structure of the sulfate was deduced from its solvolysis to the starting material, and its acetylation and subsequent solvolysis to 16alpha-hydroxydehydroepiandrosterone 16-acetate. All procedures are suitable for large scale synthesis without the use of microorganisms.

Androgens↗
PubMed1978

Androgen metabolism in sheep.

3H-Testosterone (3H-T) plus 14C-androst-4-ene-3,17-dione (A-dione) and 3H-epi-testosterone (17alpha-hydroxy-4-androsten-3-one) (epiT) plus 14C-T were injected intravenously into two male sheep with bile fistulae, respectively. Urine and bile samples were collected at intervals for 4-8 hours and analyzed by the use of DEAE-Sephadex A-25 and Lipidex 5000 columns, TLC, and paper chromatography; the aglycones were identified by co-crystallization with authentic standards. Five fractions were obtained from urine and bile: unconjugated, glucosiduronates, sulfates, sulfo-glucosiduronates and disulfates. In urine, the major conjugates were glucosiduronates, while sulfates predominated in bile. About 80-90% of recovered radioactivity was found to be either glucosiduronates or sulfates. Among the metabolites identified, epi-T was the principal one, accounting for 10-15% of the administered doses. Conversion to 17alpha-hydroxysteroids thus appears to be a major route of metabolism of the androgens administered in sheep. Other metabolites in the glucosiduronate and sulfate fractions were androsterone, etiocholanolone (3alpha-hydroxy-5beta-androstan-17-one), 5beta-androstane-3alpha,17beta-diol, two unknown diols and polar metabolites. The results indicated that androgen metabolism is somewhat unusual in sheep, as compared with other animals and the human.

Androgens↗
PubMed1978

Testosterone metabolites in dog bile.

Testosterone-1,2-3H was injected intravenously into a male dog with a bile fistula and bile and urine collected. The radioactivity was excreted preponderantly in bile (52% of the injected dose) in 6 hours; only 12% appeared in the urine. Methods to study the biliary metabolites of testosterone in this and other animals were developed. Satisfactory conjugate patterns were obtained by fractionation on DEAE-Sephadex A-25 columns using two different elution systems. In addition to an unchanged fraction, six different monoglucuronide fractions were separated. No other conjugates were isolated. Lipidex 5000 column chromatography, TLC and paper chromatography were used for the isolation and purification of aglycone metabolites, which were further identified by co-crystallization methods. The biliary metabolites of testosterone were epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one), etiocholanlone (3alpha-hydroxy-5beta-androstan-17-one), 5alpha-androstan-3beta, 17beta-diol, 5beta-androstan-3alpha, 17beta-diol and 5beta-androstan-3beta,17beta-diol.

Androgens↗
PubMed1977

A steroid structure which refutes the isolation of C(17)-C(20) rotational isomers.

Isolation of two C(17)-C(20) rotamers of 20-methyl-20-(2-hydroxyethoxy)-5-pregnene-3beta, 17alpha-diol has been reported. X-Ray analysis of a diacetate derivative of one of the "rotamers" shows that the actual structure is 3beta-acetoxy-17aalpha-(2-acetoxyethoxy)-17alpha,17abeta-dimethyl-D-homo-5-androsten-17beta-ol (C28H44O6). Thus, although this investigation refutes the existence of C(17)-C(20) rotamers, it suggests a possible new pathway for D-homo steroid synthesis.

Homosteroids↗