Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
  • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
  • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
  • C07H19/06—Pyrimidine radicals

Definitions

• the invention provides a process for selectively removing a 5-benzoyl group from a 1-(2,3- anhydro-5'-O-benzoyl-lyxofuranosyl) 2 ketopyrimidine nucleoside by reaction with a nitrogen base without cleaving the 2',3 '-anhydro group.
• a 1-(2',3'-anhydro-5-O- benzoyl-B-D-lyxofuranosyl)-2-ketopyrimidine nucleoside is converted to the corresponding 1-(2',3'-anhydro-,B-D- lyxofuranosyl)-2-ketopyrimidine nucleoside by reaction with ammonia at about 0 C.
• Equation 1 A representative embodiment of the process of this invention is as shown in the following Equation 1:
• the pyrimidine base, uracil, depicted above can be replaced by any pyrimidine base having a keto group in the 2-position, e.g., other 2-ketopyrimid ine bases such as cytosine, azauracil, thymine, S-fluorouracil, other substituted uracil-s, and the like.
• Y Letting the symbol Y signify this variable, the general representation of the process of the invention is as shown in the following Equation 2:
• the process of the invention contemplates aminolysis (including ammonolysis) of, for example, l-(2',3-anhydro-5'-O-benzoyl fi-D lyxofuranosyl)uracil, 1-(2',3'-anhydro-5'-O-benzoyl-fi-D-lyxofuranosyl)thy: mine, 1-(2',3'-anhydro-5-O-benzoyl-B-D-lyxofuranosyl)- S-fluorouracil, 1-(2',3'-anhydro-5'-O-benzoyl-B-D-lyxofuranosyl)cytosine, and the like.
• the process is novel because it was not heretofore known in the art. It is useful because it provides 1-(2',3'-anhydro-lyxofuranosyl)-2-ketopyrimidine nucleosides that can be converted into therapeutic agents.
• the process of the invention is unobvious, because it was not known that aminolysis of a 1-(2,3-anhydro 5'-O benzoyl-lyxofuranosyl) -2-ketopyrimidine nucleoside could be carried out under temperature conditions which would yield the corresponding 1- 2,3 -anhydro-lyxofuranosyl) -2-ketopyrimidine nucleoside.
• the art well knows the removal of acyl groups from nucleosides with alcoholic ammonia and amines; and the art well knows the reaction of 2',3-anhydronucleosides with alcoholic ammonia and amines to form amino deoxy-nuwithout cleaving the 2',3-anhydro (i.e., 2',3-epoxide) linkage and forming an amino deoxy-lyxofur-anoside.
• the novel process of this invention is effected by reacting a 1-(2,3-anhydro-5-O-benzoyl-1yxofuranosyl)-2- ketop-yrimidine nucleoside with .a nitrogen base at a temperature in the range of about -20 C. to about 25 C.
• a convenient and preferred temperature for the reaction is about 0 C.
• Nitrogen bases suitable for the reaction include primary and secondary amines, ammonia, and hydrazine, said nitrogen bases being characterized ⁇ by having dissociation constants in water (K in the range about 1.0 10 to about 1.0 10- Nitrogen bases having dissociation constants in water (K in the range about 1.0x 11) to about 1.0 l0- are preferred.
• suitable primary and secondary amine are methylamine, dimethylamine, ethylamine, di-
• pentylamin'e isopentylamine, benzylamine, cyclohexylamine, ethylenediamine, p-phenylenediamine, piperazine, piperidine', and the like.
• the 1-(2',3+anhydro-5'-'O- benzoyl-lyxo-furanosyl)-2-ketopyrimidine and a nitrogen base are reacted in the presence of an inert solvent, illustratively an alkanol, e.'g., methanol, ethanol, propyl alcohol, and the like.
• the debenzoylated 1-(2 ,3'-anhydro-lyxofuranosyl)-2-ketopyrimidine is re covered from the reaction mixture by removing the solvent (e.g., evaporation) and purifying the product by conventional methods such as solvent extraction, solvent evaporation, and crystallization.
• solvent e.g., evaporation
• the 1-'(2',3'-anhydro-5'-O benzoyl-B-D-1yxofuranosyl) uracil of Formula In is a known compound. It can be prepared according to the method described by Codington et al., J. Org. Chem. 27, 163 (1962). According to a preferred method, 2',3',5'-trimesyloxyuridine [1-(2', 3',S'tri-O-mesyl-B-D-ribofuranosyl)uracil] is heated, for a short time at to C., with sodium benzoate according to the method described by Codington et al., J.A.C.S.
• EXAMPLE 1 Ammonolysis of 1 (2',3-5'-O-benzoyl-B-D-lyxofumnosyl) uracil to produce 1-(2',3-anhydro-fi-D-lyxofuranosyl)uracil Two mixtures, one consisting of 41.3 g. (0.125 mole) of 1-v2',3'-anhydro-SObenzoyl-B-D-lyxofuranosyl)uracil and 1.9 l. of methanol (previously saturated with anhydrous ammonia at C.) in a stoppered 3-1. pressure flask, the other consisting of 14.8 g.
• the evacuated syrup was then thoroughly dispersed in a mixture of 150 ml. of chloroform and 75 ml. of water.
• the chloroform was permitted to separate and was removed.
• the aqueous layer was extracted times with fresh 100-ml. portions of chloroform.
• the aqueous layer thus obtained was a yellowish partially emulsified mixture. It was treated was activated charcoal and the mixture was filtered through a diatornaceous earth filter aid (Celite modified by two washings with 6 N hydrochloric acid, separate washings with water, warm:methanol, and ether, and drying).
• the filter cake was washed with water and the washings were combined with the original filtrate and refrigerated at 0 C. overnight.
• GEL-1 Green oil mull

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Biochemistry (AREA)
• Biotechnology (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Molecular Biology (AREA)
• Saccharide Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)

Priority Applications (7)

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Publications (1)

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Cited By (2)

• 1964
  • 1964-12-18 US US419552A patent/US3288781A/en not_active Expired - Lifetime
• 1965
  • 1965-11-24 GB GB49968/65A patent/GB1114870A/en not_active Expired
  • 1965-11-26 IL IL24689A patent/IL24689A/xx unknown
  • 1965-12-16 DE DE19651620617 patent/DE1620617A1/de active Pending
  • 1965-12-16 NL NL6516393A patent/NL6516393A/xx unknown
  • 1965-12-16 CH CH1738565A patent/CH460788A/de unknown
  • 1965-12-17 FR FR42783A patent/FR1460359A/fr not_active Expired

Non-Patent Citations (1)

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