Tetracycline sulfate hydrate forms molecular addition complexes with a wide range of organic compounds containing electronegative atoms in the molecule. The complexes exist only in a solid state and to these complexes a clathrate-like structure is suggested, in which the clathrate-forming substance is tetracycline sulfate hydrate and the enclosed molecule is a complexing agent, from the following facts : The smaller molecular volume and the limiting size of the complexing agent for the complex formation, the molecular ratio of 2 : 1 for tetracycline sulfate and complexing agent, the similarity of crystal structures of the complexes, and the identity of the diffraction patterns of the complexes with that of tetracycline sulfate hydrate that crystallize only in the co-presence of certain nitrogenous compounds.

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1) 7-Substituted 2-methyl- or 2-phenyl-oxazolo [4, 5-c] pyridines were prepared from 3, 5-dinitro-4-hydroxypyridine and some of them were hydrogenated over palladium-carbon or Raney nickel. 2) By examination of the hydrolysis products of 2-methyl-7-nitro (or bromo)-oxazolo-[4, 5-c] pyridine monomethiodide and 2-methyloxazolo [4, 5-b] pyridine monomethiodide, it was confirmed that methyl iodide combined with nitrogen atom in the pyridine ring of oxazolopyridine system.

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Presence of N-glucuronide in the urine of man and rabbit was proved using both 4, 4'-diaminodiphenyl sulfone and 4, 4'-diaminodiphenyl sulfoxide. Further, presence of N-sulfamate was presumed in the human urine.

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Metabolic difference between Promin and 4, 4'-diaminodiphenyl sulfone was investigated using urine and plasma of rabbits. It was clarified that Promin is metabolized mainly to N-glucoside of 4, 4'-diaminodiphenyl sulfone, receiving desulfonation. Further, N-conjugation was not clearly proved, being different from 4, 4'-diaminodiphenyl sulfone which was metabolized to mono-N-conjugates.

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(α-Methylbenzyl) succinic acid was synthesized by (A) condensation of ethyl bromoacetate and diethyl (α-methylbenzyl) malonate, and (B) condensation of (1-bromoethyl) benzene and ethyl acetylsuccinate, and its threo- and erythro-isomers were isolated.

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The configuration of the diastereoisomers, (Ia) and (Ib), of (α-methylbenzyl) succinic acid was determined by preparing them by the cis-reduction of cis- and trans-(α-methylbenzylidene) succinic acid, (IIa) and (IIb). It was also found that the Schwenk-Papa reduction of (IIa) and (IIb) proceeded stereospecifically and cis-addition of hydrogen to the double bond was observed. This stereospecificity of the reduction was further confirmed in other cases.

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A method was investigated for the synthesis of (α-methylbenzyl) succinic acid (VII) by dehydration, hydrolysis, and hydrogenation of 3-(α-methylbenzyl) malic acid (XI). Dehydration of 3-(α-methylbenzyl) malic acid (XI) by boiling with acetic anhydride yielded cis- and trans-isomers of (α-methylbenzylidene) succinic anhydride (XII) and (α-methylbenzyl) maleic anhydride (XIII), which were converted to the corresponding dicarboxylic acids by hydrolysis with water.

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The configurations of (Ia) and (Ib) were confirmed by the aromatization of these compounds to the same naphthalene derivative (IX) and by the transformation of (Ia) to cis-1-methyl-1, 2, 3, 4-tetrahydro-2-naphthoic acid (XVIa), which was prepared by the cis-reduction of 1-methyl-3, 4-dihydro-2-naphthoic acid (XVII).

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7-Bromostigmasteryl benzoate obtained by bromination with N-bromosuccinimide was converted to stigmastatrienyl benzoate by treatment with collidine or pyridine. Degradation of 7-pyridinium bromides of stigmasteryl benzoate and cholesteryl benzoate was also carried out. Substitution of 7α-bromocholesteryl benzoate and 7ξ-bromostigmasteryl benzoate with ammonium thiocyanate was also examined. (Received September 24, 1960)

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Bromination of cholest-5-en-7-one and 3β-hydroxycholest-5-en-7-one benzoate with N-bromosuccinimide was carried out. Resulting bromo derivatives were converted to dienones, bromo-dienones, or anilino-dienones. The bromo-dienons were assigned 6-bromo-or 4-bromocholesta-3, 5-dien-7-one structure and their characteristic infrared absorptions were summarized. Epoxidation of cholesta-3, 5-dien-7-one was also examined.

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Fission of 3α, 4α-epoxycholest-5-en-7-one with hydrobromic acid gave a bromohyrin, whose acyloxyl derivatives were converted to 4-bromocholesta-3, 5-dien-7-one, particularly to 6-bromocholesta-3, 5-dien-7-one accompanied with bromine migration. Also, 3, 4-dibromocholest-5-en-7-one was converted to 6-bromocholesta-3, 5-dienone. The ultraviolet and infrared absorption spectra of these bromo derivatives were summarized.

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Bromination of cholesta-3, 5-dien-7-one (I) with N-bromosuccinimide afforded 2-bromocholesta-3, 5-dien-7-one (II) and dehydrobromination of (II) yielded cholesta-1, 3, 5-trien-7-one (III), whose structure was established by leading it to the maleic anhydride adduct (VII) and hydrogenation.

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trans-2-Methyl-octahydro-5 (1H)-isoquinolone was prepared and configuration of the ring juncture was discussed. Reduction of this base gave two isomers of trans-2-methyl-decahydro-5-isoquinolinol.

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N, N-Bis (2-chloroethyl) isoxazolidinium chloride and its related compounds were prepared, and their latent anti-tumor activity was tested on Yoshida sarcoma.

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dl-Lyxose and dl-xylose were synthesized by the cis-hydroxylation of dl-trans-1, 1-diethoxy-5-tetrahydropyran-2-yloxypent-3-en-2-ol (XII) and it was anticipated that they would also be formed by the trans-hydroxylation of dl-cis-1, 1-diethoxy-5-tetrahydropyran-2-yloxypent-3-en-2-ol (IV).

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1) The leuco-type strain of Er. ashbyii was cultivated for 120 hours in the same manner as the yellow-type strain and about 24g./L. (medium) of the wet mycelium was obtained. Use of corn-steep liquor instead of meat extract raised the yield, the quantity of the mycelium amounting to 40.5g./L. in 94 hr. 2) The mycelium of the leuco-type strain and that of the yellow-type strain were extracted and the extracts were chromatographed to investigate the amino acids therein. It was found that the former contained various amino acids but not hydroxykynurenine, and in its instead it contained proline which was absent in the yellow-type strain. 3) Presence of riboflavin in the leuco-type strain was confirmed by paper partition chromatography and the amount of riboflavin in the spot was determined, finding ca. 3γ/g. (wet mycelium). 4) A crude enzyme solution was prepared from the leuco-type and yellow-type strains, and the solutions were acted on 6, 7-dimethylribolumazine. It was found that both enzyme systems have the ability to produce riboflavin and 6-methyl-7-hydroxyribolumazine, but the enzyme system from the yellow-type strain is a little more active than that from the leuco-type strain. The enzyme solutions were also acted on a mixture of 4-ribitylamino-5-aminouracil and acetoin. In this case, the solution from the yellow-type strain produced riboflavin and 6-methyl-7-hydroxyribolumazine, but the solution from the leuco-type strain yielded no such substances.

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It was previously found that reaction between 6, 7-dimethylribolumazine and a crude enzyme prepared from the mycelium of Er. ashbyii produced riboflavin and 6-methyl-7-hydroxyribolumazine and reported that the enzymic reaction yielded a considerable amount of riboflavin without addition of any carbon donor. Later, the products in the enzymic reaction were investigated by paper partition chromatography and a bluish green fluorescent spot with Rf 0.10 was detected besides the known substances, and the newly found substance was assumed to be the dimeride of 4-ribitylamino-5-aminouracil described in part XLI of this series.

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