The orientation and relative strength of participation of neighboring groups during the formation of azoline ring by treatment of N-thiobenzoyl, N-benzoyl, and N-benzimidoyl derivatives of dl-2-aminocyclohexanols and dl-2-aminohexanethiols with phosphorus pentoxide or thionyl chloride were comparatively examined with the reaction products obtained (Table I and II). The relative intensity was found to be in the descending order of thiobenzoyl, benzoyl, and benzimidoyl by treatment with phosphorus pentoxide and in the descending order of benzoyl, thiobenzoyl and benzimidoyl in the case of thionyl chloride. Participation of SH group to Cα (cf. Chart 1) is stronger than that of OH group. Acyl migration from N to O or N to S was examined and it was found that in N-acylated derivatives of dl-2-aminocyclohexanol all the derivatives tested underwent retention to give O-benzoyl derivative. In N-benzoylated compound of dl-2-aminocyclohexanethiol, this was retention and the trans compound gave S-benzoate, while cis compound produced only cis-thiazoline.
The epimeric dl-1-phenyl-2-aminopropanethiols (threo-XI and erythro-XI), corresponding to thiol derivatives of norephedrine, were synthesized by various routes and their configurations were assigned from their formation mechanism and chemical properties. The substance of C10H11ONS, formed by the action of carbon disulfide and potassium hydroxide on epimeric dl-1-phenyl-2-aminopropanols (threo-I and erythro-I), was found from infrared spectra and reaction routes to be the epimeric dl-4-methyl-5-phenyloxazolidine-2-thione, with no change in the steric configuration, and not the epimeric dl-4-methyl-5-phenylthiazolidine-2-one (threo-XIV and erythro-XIV) obtained by one inversion.
In accordance with N-alkylation of dl-2-methyl-4, 5-cyclohexanothiazoline, alkyl iodide was applied to dl-2-phenyl-4, 5-cyclohexanothiazoline and corresponding thia-zolinium salt was obtained, which was derived to dl-2-monoalkylaminocyclohexane-thiol. The reaction did not progress in both cis and trans compounds when methyl or ethyl iodide was used, while the alkylation did not proceed with isopropyl iodide due to steric hindrance and decomposition of the iodide itself preceded. Acyl migration of N-benzoylated compound of dl-2-monoalkylaminocyclohexanethiols was also examined.
A series of new compounds obtained by application of hydrazine hydrate to 2, 3-dimercaptoquinoxaline were examined for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Candida, Aspergillus, Trichophyton, Mycobacterium tuberculosis, strain 607 and human strain. Of the compounds tested, 2-mercapto-3-hydrazinoquinoxaline was effective against all the microörganisms tested, indicating it to be a new type of antibacterial substance. Various hydrazones of this compound were prepared to examine variation in antibacterial activity. It was thereby found that hydrazones of aliphatic ketones and aldehydes possessed antibacterial spectrum and activity similar to the original substance, while such properties were lost in corresponding aromatic derivatives. All the hydrazones showed antibacterial activity against human-type tubercle bacilli to the same degree as or better than Tibione, and there seemed to be small variation among the hydrazones. Antibacterial activity against strain 607 of tubercle bacilli was found to be of the same degree as its activity against gram-positive and -negative bacteria.
Determination of Oleandomycin was attempted by the following process. A 0.5-cc portion of 1% hydrochloric acid solution of sulfanilic acid was diazotized with 1cc of 1% aqueous solution of sodium nitrite, for 2 minutes in ice water, the resultant solution was shaken with 1cc. of 0.40 N aqueous solution of sodium hydroxide and 0.5cc. of pyridine, 2cc. of aqueous solution of Oleandomycin phosphate (25-300γ/cc. sample solution) was added, and after warming at 30° for 30 minutes, this was shaken vigorously with 3cc. of ethanol and 1cc. of 0.5% aqueous solution of ascorbic acid. This solution colored pink and showed absorption at 532mμ, and the absorbancy was found to be proportional to the concentration, within a range of 25-300γ/cc. of sample concentration. Comparison of values of determination by the present process and by bioassay, using aqueous solution of Oleandomycin phosphate left to stand in a refigerator, at room temperature, and at 37°, for a long period to effect some degree of decomposition, gave well agreeing results. It was found that the aqueous solution of Oleandomycin, when stored at a low temperature, shows almost no decrease in potency even for a long period of time.
Preparation and purification of callicrein from hog pancreas and its content in various organs were described in the preceding paper. It was now found that callicrein is selectively precipitated with acrinol (2-ethoxy-6, 9-diaminoacridinium lactate) and that this is an effective method for its purification. Callicrein of ca. 200U/mg. purity so obtained is positive to all coloration reaction for proteins in general and had absorption maximum in the region of 281 mμ in its ultraviolet spectrum.
Kinetic studies were made on the reaction of nitrous acid and lecithinase, purified from Formosan cobra venom. The decreased activity of lecithinase in the presence of excess nitrous acid in acetate buffer is a first-order reaction and its reaction rate is extremely slow as compared to deamination reaction, the half-life being 270 minutes at pH 4.0 and 390 minutes at pH 4.4. The lecithinase partially inactivated by nitrous acid does not recover its activity by application of hydrogen sulfide. These facts suggest that the principle of lecithinase activity is independent of amino or mercapto group and is situated in the phenol, that is, in tyrosine.
Examinations were made on the improvement of a process of preparation of 4-iodothymol, which has extremely strong ascaricidal action against earthworm and hog ascaris and is yet weak in toxicity against animals (mice and rats), and its anthelmintic activity against human parasitic worms, especially ascaris. As a result, improvement of preparative process raised the yield of 4-iodothymol to 88.5%. Anthelmintic rate in those infected with hookworm was 53.3-62.5% while that in those infected with ascaris was 20.0-46.6%, showing that it was quite effective against hookworm. The side effect was extremely small and the limitation of food or simultaneous administration of laxative for this treatment is not necessary. Therefore, it is believed that much can be expected of 4-iodothymol as a remedy for hookworm infection.
It was found that vitamin B6 is not so stable as had been believed in acid range, in the presence of oxygen, and that it colored with passage of time. The degree of coloration increased with passage of time, the rate constant of coloration was affected by pH of the solution, and the maximum rate constant of coloration in the range of pH 4.5-7 was indicated at around pH 5.5. Coloration of aqueous solution of vitamin B6 due to the hydroxyl in 3-position in its molecule and the maximum coloration at pH 5.5 is believed to be due to vitamin B6 taking a different structure in a solution of that pH.
Crude wax (A) was obtained in 2% yield from dried leaflets of a fern, Diplopterygium glaucum (Japanese name “Urajiro”). It melted at 80-86°, gave acid value of 9.9, ester value of 51.9, and oxygen content of 7.7%, and belongs to a non-estolide type. Treatment of (A) as shown in Chart 1 showed that it was composed of approximately 30% of free (non-ester) component (B) and 70% of wax ester (C). Liquid chromatography of (B) through alumina separated it into nonacosan-10-one, nonacosane, pentatriacontane, nonacosan-10-ol, and triacontan-1-ol, the first one being contained in 12% and the first example of it as a plant component. The wax ester (C) was chiefly composed of the ester of triacontan-1-ol of triacontan-1-oic acid and also yielded hexacosan-1-oic acid and hexacosan-1-ol. The presence of C24, C28, and C32 compounds was also presumed.
A crude wax (A) was obtained in 0.42% yield from the dried leaflets of Cycas revoluta. It melted at 78-81° and gave acid value of 40.5, ester value of 147.3, and-oxygen content of 15.7%. It was an estolide type of wax generally found in the conifers. Treatment of (A) as shown in Chart 1 separated it into 70% of acid estolide (D+C), 16% of neutral estolide (J), and 4% of free component (H). The acid estolide is composed of 90% of juniperic acid and the rest of sabinic acid, corresponding to the estolide with 4-6 moles of juniperic acid. The neutral estolide contained 1, 16-hexadecanediol besides the foregoing two hydroxy acids. The free component yielded nonacosane, nonacosan-10-one, nonacosan-10-ol, and octacosan-1-ol. The leaflets also afforded, besides (A), a high-molecular wax (B) in 0.05% yield and its chief component is an estolide with about 8 moles of juniperic acid.
The crude wax, obtained in 1.5% yield from the leaves of Hinoki (Chamaecyparis obtusa), was saponified and treated as shown in Chart 1, and, besides the components already known, lauric acid, triacontanoic acid, dodecane-1, 12-dioic acid, nonacosane, pentatriacontane, and nonacosan-10-one were isolated (Table I). This is the first example of isolation of dodecane-1, 12-dioic acid as a plant component. The content of each component calculated from alumina chromatographic results is shown in Table II.
A wax was obtained in 0.7-1.0% yield from dried leaves of Ginkgo biloba, and 10% of acid component, 15% of wax ester, and 75% of non-ester component were separated from the wax. The chief component is ginnol (nonacosan-10-ol), and nonacosane, nonacosan-10-one, and octacosanol were also obtained. A wax was obtained in 0.15% yield from the fresh leaves of Ephedra gerardiana and the wax afforded 40% of a free component, containing nonacosanol as the chief component besides nonacosane and triacontanol. Physical constants of all these and other waxes are shown in Table I. The acid and ester values, and percentage of wax differ between the estolide and non-estolide types, and low-molecular components soluble in petroleum benzine differ in content according to different plants. The percentage content of nonacosan-10-ol is extremely high in the two kinds of wax mentioned above. It was found that liquid chromatography using alumina is effective in the study of leaf waxes.
The presence of the estolide reported by Bougault and Bourdier and as well as its carboxylic acid esterified with higher alcohol, was detected in the leaf wax of Pinus Thunbergii and they were respectively designated acid and neutral estolides. It was revealed through the present work that this neutral estolide was distributed widely in the estolide-type conifers as leaf-wax component (Table II).
Generation of wetting heat when a tablet enters water results in the warming of air entrapped inside the tablet with consequent increase of volume and this becomes the cause of disintegration of tablets. Aluminum silicate generates a great deal of wetting heat but it has a special characteristic of losing this wetting heat by compression. The values of watting heat calculated from adsorption isotherm of compressed samples reported in Part I of this series are indicated in Table III, and the experimental values of some samples, before and after compression, measured by Bunsen's ice calorimeter, are indicated in Tables I and II. They all indicate decrease of wetting heat by compression. Since the specific heat of these samples was 0.171, internal temperature of a tablet is considered to become fairly high.
A method was found by which the value of wetting heat is calculated graphically from adsorption isotherm, using the change of Gibbs' free energy in adsorption. Prior absorption of moisture by a tablet decreases generation of wetting heat. In the above method, wetting heat generated by a sample which has absorbed moisture can be calculated by integration on the graph eliminating the primary moisture. In one example of aluminum silicate sample, a presence of a slight moisture resulted in marked decrease of wetting heat. This is due to the type of adsorption isotherm and it should be clear from Fig. 1 that the substances indicating adsorption isotherm of BET II-and IV-types show marked decrease of wetting heat by initial moisture.
Aspirin can be tabletted by itself but the tablet does not disintegrate because the contact angle of Aspirin is over 90° and water cannot penetrate inside the tablet. When Aspirin is tabletted with starch, whose contact angle is 80-85°, water will penetrate through a canal made of starch grains and cause disintegration of such a tablet. The use of talc is known to cause poor disintegration and this is primarily due to the fact that talc does not adhese to starch or crystals, forming aggregate of talc itself and because its contact angle is over 90°, preventing penetration of water.
Relationship between structure of azophenol derivatives and antifungal activity against Hyphomycetes was examined and following observations were made: (i) Introduction of various functions into toxic groups failed to increase antifungal activity; (ii) one hydroxyl group is necessary for activity; (iii) bis-compound is not effective; (iv) introduction of nitro, chlorine, or bromine into phenyl ring increases antifungal activity; and (v) naphthyl ring can replace phenyl group in this series. 2, 4-Dichloro-4′-hydroxyazobenzene was found to be an effective antifungal substance and this compound inhibited the growth of Hyphomycetes in 2, 000, 000-fold dilution.
Dry distillation of acetyl and benzoyl derivatives (I) of o-aminophenylacetic acid with equal amount of soda lime affords 2-methyl-and 2-phenyl-indole (II) in 66 and 59% yield, respectively, but the same reaction of N-acetyloxindole (III) failed to give 2-methylindole, resulting in recovery of the starting material. Similarly, 2-methyl-and 2-phenyl-dihydroquinoline (VI and VII) was obtained in 66% and 57% yield, respectively, from acetyl and benzoyl derivative (V) of o-aminophenylpropionic acid. Catalytic dehydrogenation of (VI) or (VII) over palladium-asbestos in safrole easily gave the corresponding quinoline compounds, but the acetyl compound (IX) of o-aminocinnamic acid failed to undergo cyclization to the corresponding quinoline compounds (VII). This is probably due to the trans configuration of (IX). The structure of 2-R-dihydroquinoline derivatives here formed, whether it is represented by (VI) or (VII), was examined from infrared and ultraviolet spectral data. Compounds with a substituent with -I effect, such as methyl, in α-position, are mainly of α, β-enamine type (VII) with distinctly positive Liebermann reaction but on allowing to a, β-enamine type (VII) with distinctly positive Liebermann reaction but on allowing to stand over night with dilute hydrochloric acid or on warming for a short time, the Liebermann reaction becomes negative. Derivatives with electrophilic substituent, like phenly, are all azomethine type (VI) and are negative to Liebermann reaction. The salts of (VII), such as perchlorate, form immonium salt.
Acylation of δ-aminovaleric acid is difficult either by the Schotten-Baumann reaction with acetic anhydride and fatty acid chloride or with ketene but aliphatic acylated compound of this amino acid was finally prepared by the Schotten-Baumann reaction with acid chloride after esterification. Dry distillation of this acylated derivatives with equal amount of soda lime gives 2-alkyl-Δ1(or Δ2)-tetrahydropyridine containing γ-coniceine in comparatively high yield. It was doubtful whether the base formed corresponded to formula (I) or (II). Various properties of the compound, such as its ring cleavage to the amino-ketone compound with acid chloride agreed with the α, β-enamine type (II), reported in past literature, but infrared and ultraviolet spectral data indicate that compounds with a substituent with -I effect, such as methyl, in α-position preferentially take the azomethine type (I), while those with electron-withdrawal group, such as phenyl, completely form the azomethine type. Suitable dehydrogenation of the base (I or II) thereby formed gives pyridine compound, such as α-picoline, while catalytic reduction over palladium-carbon gives piperidine derivative, such as dl-coniine.
Galactose was acetylated to β-pentaacetyl-D-galactose which was brominated with glacial acetic acid saturated with hydrogen bromide at 0° to from α-acetobromo-D-galactose. Condensation of this brominated compound with fatty alcohols by the König-Knorr reaction, using silver oxide in chloroform, afforded alkyl 2, 3, 4, 6-tetra-O-acetyl-β-D-galactopyranosides, which was finally deacetylated with 0.01N sodium methoxide, forming 10 kinds of alkyl β-D-galactopyranosides; viz. butyl compound, m.p. 101°; pentyl, m.p. 117°, hexyl, m.p. 118.5°; octyl, m.p. 109.5°; decyl, m.p. 152° (t.p. 103°); dodecyl, m.p. 159° (t.p. 101.5°); tetradecyl, m.p. 168° (t.p. 102°); hexadecyl, m.p. 161° (t.p. 102°); octadecyl, m.p. 154° (t.p. 103°); and cis-9-octadecenyl, m.p. 138 (t.p. 56°). Similarly, alkyl β-D-glucopyranosides and their acetyl derivatives were prepared; viz. tetradecyl compound, m.p. 150° (t.p. 83°); hexadecyl, m.p. 145° (t.p. 82.5°); octadecyl, m.p. 120° (t.p. 81.5°); and cis-9-octadecenyl as a syrup. Their acetyl derivatives were: Tetradecyl, m.p. 69°; hexadecyl, m.p. 73.5°; octadecyl, m.p. 79.5°; and cis-9-octadecenyl, b.p0.05 252°. (t.p.: transition point). Of these, alkyl galactosides with larger number of carbon than decyl, and alkyl glucosides are considered to form liquid crystals.
N-Methyllaurotetanine (II), the phenolic aporphine-type base contained in trace amounts in Litsea cetrata BL. of northern European origin, was synthesized in racemic form by the route shown in Chart 1. During the synthesis, a by-product of Pachorr's phenanthrene-cyclization was a substance corresponding to laudanine (XII), a benzylisoquinoline-type base.
Subcutaneous injection of bis(2, 4-dihydroxyphenyl) disulfide (I), bis(4-hydroxyphenyl) disulfide (II), and diphenyl disulfide (III) in normal and castrated male rats showed that these compounds had no androgenic activity but increased the weight of levator ani muscles. This may be considered as a myotrophic activity. Such activity is present in stilbestrol, a synthetic estrogen, and in hexestrol (IV) tested by the present author, but not in estradiol 3-benzoate, the natural estrogen. Therefore, it is assumed that the factor responsible for increasing the weight of levator ani muscle is independent of androgenic or estrogenic activities. Administration of (I) and (IV) in castrated female rats in doses showing the same potency by the Allen-Doisy method and measurement of their uterine weight showed that the weight of uterus in the group of rats given (I) was no different from that of the control while that of a group of rats given (IV) was markedly greater. Similarly, administration of (I) and (IV) in normal male rats and measurement of their testicular weight showed that the weight of testicle in the group given (I) was no different from that of the control, while the testicle in the group given (IV) had atrophied. These facts show that although (I) and (IV) are both synthetic estrogens, they differ in their biological activity.
Compounds like biphenyl, diphenyl sulfide, diphenyl disulfide, diphenyl trisulfide, which do not have steroidal skeleton, possess estrogen-like activity. Of the compounds with phenyl bonded to sulfur atom, those having the most suitable distance (8.55Å) between two radicals in the molecule, i.e. disulfide compounds, showed the strongest estrogen-like activity. Position of the substituent on the ring had little effect on the potency, while OH group increased such activity. The activity seemed to be weakened by the effect of a substituent in the order of Cl, Br, I>NO2>COOH>CH3. Some of the diphenyl disulfide derivatives used in the present experiments were obtained by reduction of benzenesulfonyl derivatives with red phosphorus and hydrobromic acid, a modification of Kawahara's method using red phosphorus and iodine.
Phenol derivatives possessing a long-chain alkyl or -COR group in the ortho or para position of phenol, β-diketone derivatives having -COCH2COR group, and monoketo acid derivatives possessing -CO(CH2)nCOOR group were synthesized and their antibacterial activity against Staphylococcus aureus and antifungal activity against Trychophyton were examined.
1-Carbamoyl-4-acylthiosemicarbazide (II) was prepared by the reaction of semicarbazide and acyl isothiocyanate, and its cyclization reaction was examined. Treatment of (II) with sodium hydroxide solution afforded 3-aryl (or alkyl)-1H-1, 2, 4-triazole-5-thiol (III), with acetic anhydride gave 2-acylamido-5-methyl-1, 3, 4-thiadiazole, and reaction of (III) with methyl iodide gave the S-methylated compound. Treatment of (II) with conc. sulfuric acid or conc. hydrochloric acid gave a substance assumed to be 2-acylamido-1, 3, 4-thiadiazol-5-ol (VIII), besides (III). Hydrolysis of 2-benzamido-1, 3, 4-thiadiazol-5-ol (VIIIa) with conc. hydrochloric acid afforded benzoic acid and thiosemicarbazide hydrochloride, and 2-amino compound was not isolated. The benzoate of (VIIIa) agreed completely with the dibenzoylated compound of m.p. 177°, obtained by hydrochloric acid hydrolysis of 1-carbamoylthiosemicarbazide of 1-(N-phenylcarbamoyl) thiosemicarbazide.
1-Isopropylidene-2, 2-diacylhydrazines were prepared and their hydrolysis was examined. It was found that one of the acyl groups on N2 underwent rearrangement at the time of liberation of acetone to form 1, 2-diacylhydrazine but such rearrangement was not detected in 1-isopropylidene-2-benzoyl-2-phenylhydrazine.
A new crystalline substance was obtained from the mother liquor left after removal of wax from an extract of a fern, Diplopterygium glaucum. It was obtained in 0.02% yield, corresponded to the composition of C30H52O, m.p. 254-256°, [α]D25 +34.9 ±0.9° (c=0.039, CHCl3), and it was named diplopterol. It colored reddish purple by the Liebermann reaction, similar to ursane or oleanane but does not color with tetranitromethane. Its infrared spectrum (in Nujol) exhibited absorption maxima at 3450 and 1150cm-1. Its acetylation or benzoylation gave the same hydrocarbon of C30H50, and its oxidation with chromium trioxide afforded a ketone. These facts indicate the presence of one hydroxyl and this hydroxyl was found to be easily dehydrated.
The oil (I) of b.p2.5-3 96-99° was fractionated from the ethanolic extract of the rhizome of Ligusticum scoticum L. and this substance was determined as myristicin from its physical and chemical properties. Bromination of (I) in the cold gives dibromomyristicin dibromide (II) while treatment of (I) in alkali resulted in isomerization, and its bromo compound (IV) was also obtained. Permanganate oxidation of (I) gave (V), which was proved by separation of gallic acid. The fact that hydrogenation of (I) and (III) afforded the same derivative also indicates the position of double bond in the side chain. These results prove that the substance is myristicin.
Application of phosphoryl chloride to 2-hydroxymethyl-5-methylpyridine (IV), derived from 2, 5-lutidine (I), afforded the chlorinated compound (V) and application of potassium chloride to (V) gave the nitrile (VI), which formed the ester (VII) on warming in ethanol saturated with hydrogen chloride. (VI) underwent saponification and decarboxylation on heating with hydrochloric acid to form (I). The ester (VII) was also obtained on application of dry ice to lithium compound of (I) and followed by treatment with ethanol saturated with hydrogen chloride. Application of methyl iodide to (VII), in the presence of metallic potassium afforded ethyl 2-(5-methyl-2-pyridyl) propionate (VIII).
Reduction of 1, 1, 1-trichloro-2, 2-bis (2-methoxy-5-methylphenyl) ethane with zinc dust and glacial acetic acid results in the formation of a corresponding ethane compound free of chlorine with a by-product of a fluorescent compound of m.p. 157°, C18H20O2. Oxidation of the latter with potassium permanganate gives 2-methoxy-5-methylbenzoic acid, suggesting that the fluorescent compound is a stilbene-derivative. The reduction product of 1, 1, 1-trichloro-2, 2-bis (2-methoxy-5-chlorophenyl)-ethane also shows fluorescence but a fluorescent compound was not isolated. Permanganate oxidation of the crude product afforded non-fluorescent ethane compound and 2-methoxy-5-chlorobenzoic acid. The same treatment of 1, 1, 1-trichloro-2, 2-diphenylethane also affords a small amount of stilbene as the by-product.
Sulfisoxazole cannot be determined by titration with nitrous acid, a general procedure for sulfa drugs. A method for its determination was devised by deriving sulfisoxazole to N1-acetylsulfisoxazole with acetic anhydride in pyridine and titration with nitrous acid. In this method, about, 500mg. of a sample is weighed accurately, dissolved in 1.4 times (volume to weight) of pyridine with application of heat, immersed in a cold water bath of 0° to 2° for 3minutes, 0.4 times its weight of acetic anhydride is added, and the mixture is allowed to stand for 10minutes with occasional stirring. The excess of acetic anhydride is decomposed with 1cc. of water, precipitate is dissolved by addition of 25cc. of acetone, 20cc. of 10% hydrochloric acid and 10cc. of water are added, and this mixture is titrated with 0.1M sodium nitrite. The end point is when a drop of this solution dose not color yellow when placed on a p-dimethylaminobenzaldehyde test paper. Sulfisoxazole alone can be determined by this method as long as the presence of other sulfa drugs does not exceed 5%.
Oxidation of thiamine anhydride with hydrogen peroxide results in formation of sulfoxide and sulfone according to reaction conditions. Biological activity of thi-amine anhydride is about 1/100 of thiamine hydrochloride and other workers re-port that biological effect of thiamine anhydride sulfoxide is approximately equal to that of thiamine hydrochloride. Biological effect of thiamine anhydride sulfone was examined, first by in vitro regeneration of the sulfone to thiamine by liver slices, cysteine hydrochloride, or Takadiastase, but the product failed to show thiamine reaction. Attempt was then made for treatment of thiamine-deficiency in a rat but the sulfone did not show any efficacy.
A steroidal sapogenin was isolated from the leaf of Yucca filamentosa L. (Liliaceae) and it was found to be tigogenin from the measurement of physical constants of this sapogenin and its derivatives. Treatment of tigogenin with acetic anhydride to cyclize its side chain and subsequent oxidation with chromium trioxide afforded Δ16(17)-3β-acetoxyallopregn-16-en-20-one, m.p. 163°.
Administration of bis(2-hydroxyphenyl) disulfide (I), bis(2-methylphenyl) disulfide (II), bis(2-carboxyphenyl) disulfide (III), bis(4-methylphenyl) dislfide (IV), and bis(4-carboxyphenyl) disulfide (V) to male rats showed that (I), (III), and (V) effected enlargement of levator ani muscle in normal rat but (IV) did not have such effect on either normal or castrated rats. (V) also did not have any effect on castrated rats.
In order to obtain progestational hormone with durable potency, progesterone 3-monopropylene ketal (I) and 17α-hydroxy-1-dehydroprogesterone (II) were prepared. (II) was prepared first by acetylation of pregnenolone to form 5, 17 (20)-pregnadiene-3β, 20-diol diacetate, double bond at 17 (20)-position selectively epoxidized with perbenzoic acid, and hydrolyzed to 17α-hydroxypregnenolone. Oppenauer oxidation of this latter substance to 17α-hydroxyprogesterone (III) and subsequent oxidation with selenium dioxide afforded (II). Esterification of (II) is difficult that the ester of (III) was oxidized with selenium dioxide to obtain the ester of (II). Examinations of progestational activity of (I), (II)-acetate, (II)-caproate, (III)-acetate, and (III)-caproate by the modified Clauberg method showed that they had potency weaker than progesterone but examination by the modified Allen-Corner method indicated that the ester of (II) seemed to have a slightly longer duration of potency than the ester of (III).