Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D475/00—Heterocyclic compounds containing pteridine ring systems
  • C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
  • C07D475/14—Benz [g] pteridines, e.g. riboflavin

Definitions

• This invention relates to fatty acid esters'of riboflavin and to a process for preparing same.
• riboflavin is a slightly water-soluble vitamin and, therefore, has some inconveniences for food-enrichment or pharmaceutical fields.
• riboflavin may be rendered fat-soluble by esterification with fatty acids.
• a fatty acid ester of riboflavin can be prepared by reacting riboflavin with an alkanoyl halide having 4 to 20 carbon atoms. The reaction may be carried out in an inert solvent, such as benzene, chloroform or other halogenated hydrocarbons, in the presence of an acid acceptor such as pyridine. Since riboflavin has four free hydroxy groups in the molecule, it is preferable to use more than four moles of the alkanoyl halide per mole of riboflavin.
• alkanoyl halide I prefer to use those having 4 to 20 carbon atoms such as butyryl, hexanoyl, octanoyl, capryl, lauroyl, myristoyl, palmitoyl and stearoyl chloride or bromide.
• the process of the present invention also includes the use of corresponding acid anhydride instead of said acid halide.
• the riboflavin ester is recovered by evaporation of the solvent under reduced pressure or by pouring the reaction mixture into inert solvents in which the riboflavin ester is insoluble.
• those having lower alkanoyl moiety can be conveniently prepared by directly reacting riboflavin with the alkanoic anhydride in the presence of concentrated perchloric acid.
• the butyric ester of riboflavin can be obtained in high yield by adding a small amount of 60% perchloric acid into a mixture of riboflavin and butyric anhydride with stirring at room temperature and then pouring the reaction mixture into water.
• the fatty acid esters of riboflavin thus prepared may be recovered and purified by recrystallization from ether, benzene or ethanol.
• the riboflavin esters of this inven tion are substantially tasteless and odorless, and are quite soluble in many conventional solvents, such as ethanol, pyridine, benzene, chloroform, or neutral fats, in each of which riboflavin itself is almost insoluble.
• riboflavin esters of this invention have the following structural formula:
• the compounds of this invention possess vitamin B activity. When administered orally, the compounds are easily hydrolyzed with human digestive juices into riboflavin and corresponding fatty acids, and effect vitamin B activity. It has been found that the compounds are'hydrolyzed with neither saliva nor gastric juices, but with duodenal juice. Among many of the compounds riboflavin tetrabutyrate is most easily hydrolyzed. This can be illustrated by the test described below.
• each of the substrates was suspended in a mixture'of 0.3 ml. of 0.1 M phosphoric acid-buffered solution (pH 8.5) and 0.2 ml. of human duodenal juice at a concentration of 1x10- M.
• the substrate solutions were incu-' bated for 30 minutes at 37 C. and the degradation rate of each of the substrates was assayed by the lumiflavin fluorescence method (Yagi, J. Biochem., vol. 43, page It has also been found that the compounds of the invention show vitamin B activity on dietary scurvy using male albino rats.
• riboflavin tetrabutyrate increases the body weight of rats as much as free riboflavin and it prevents ariboflavinosis remarkably. However, others were found to have little growth-promoting activity.
• the blood level of total riboflavin rises more slowly, and remains at an effective level for a longer period than with free riboflavimj- Furthermore, the administered riboflavin is substantially excreted in urine for a longer period of time than is free riboflavin. For example, when 5 mg. of free riboflavin is administered to a rabbit, weighting about 3 kg., by intramuscular injection, the blood level of total riboflavin reaches a peak within 30 to 60 minutes and a substantial quantity of the given riboflavin is excreted in urine within a few hours.
• the blood level of total riboflavin reaches a peak on more than 12 hours after the injection, and 30 to 40% of the given riboflavin is excreted in urine within 24 hours.
• Example 1 1 g. of riboflavin was suspended in 300 ml. of a 1:1 mixture of pyridine-chloroform. Into this suspension, 15 g. of palmitoyl chloride in 50 ml. of chloroform was dripped at 0 C. with vigorous stirring within about 1 hour. The mixture was stirred for an additional 14- r H, 10.61 N, 4.21..
• reaction mixture was concen trated to dryness under reduced pressure and the residue was treated with mlaof 90% pyridine at 70 C.
• Example' 5 1 of riboflavin was added to 10 inl. of butyric anhy- To the mixture was added 05ml. of 60% aque-' ous solution of perchloric acid at. room temperature with .vigorous stirringi The reaction mixture was V poured into 50 nil. of water. After the orangefyellowr.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Pyridine Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Cited By (8)

Citations (2)

• 1962
  • 1962-04-10 US US186327A patent/US3189598A/en not_active Expired - Lifetime
  • 1962-07-13 DE DET22463A patent/DE1179218B/de active Pending
  • 1962-08-10 CH CH963462A patent/CH414658A/de unknown
  • 1962-09-18 GB GB35449/62A patent/GB943078A/en not_active Expired

Patent Citations (2)

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