合成路线:5) The benzoylation of 2'-deoxyinosine (I) with benzoyl chloride in pyridine gives the 5'-O-benzoyl derivative (II),which is treated with 1,1'-thiocarbonyldiimidazole (DTI) in DMF to afford the 2'-O-thiocarbonyl derivative (III).The reaction of (III) with bis(tributyltin)oxide,polymethylhydroxysilane and AIBN in refluxing dioxane yields 5'-O-benzoyl-2',3'-dideoxyinosine (IV),which is finally deprotected with anhydrous NH3 in methanol.Another microbial conversion of 2',3'-dideoxyuridine to 2',3'-dideoxyinosine by transdideoxyribosylation with hypoxanthine in a culture medium of Escherichia coli ATCC 10798 is described,and industrially applicable methods for the purification of enzymatically or microbially obtained dideoxyinosines are reported.
参考文献标题:Method for the purification of dideoxyinosine
文献作者:Tanabe,T.; Otani,M.; Arai,M.; Yukawa,T.(Ajinomoto Co.,Inc.)
参考来源:JP 1989175991
合成路线:A new synthesis of 2',3'-dideoxyadenosine has been described:The reaction of uridine (I) with methyl orthoformate and p-toluenesulfonic acid gives the cyclic orthoester (II),which is acetylated with acetic anhydride at 100 C to the acetate (III).The reaction of (III) with acetic anhydride at temperatures over 120 C yields 5'-O-acetyl-2',3'-dideoxy-2',3'-didehydrouridine (IV),which is hydrogenated to 5'-O-acetyl-2',3'-dideoxyuridine (V).
合成路线:The hydrolysis of (V) affords 2',3'-dideoxyuridine (VI),which is finally submitted to transdeoxyribosilation with adenine (VII) by means of Escherichia coli AJ-2595 microorganisms.
合成路线:2) The reaction of uridine (I) with methyl orthoformate and p-toluenesulfonic acid gives the cyclic orthoester (II),which is acetylated with acetic anhydride at 100 C,yielding the 5'-acetoxy derivative (III).The reaction of (III) with acetic anhydride at temperatures over 120 C affords 5'-O-acetyl-2',3'-dideoxy-2',3'-didehydrouridine (IV),which is hydrogenated to 5'-O-acetyl-2',3'-dideoxyuridine (V).Hydrolysis of (V) affords 2',3'-dideoxyuridine (VI),which is finally submitted to a transdideoxyribosylation with hypoxanthine (VII) by incubation in an appropriate medium with Escherichia coli AJ 2595 resting cells.
参考文献标题:The synthesis of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine
文献作者:Shiragami,H.; Shirae,H.; Irie,Y.; Yokozeki,K.; Yasuda,N.
参考来源:Nucl Acid Res Symp Ser 1988,20(20),17-18
合成路线:This compound is prepared by two related ways:1) The partial silylation of adenosine (I) with tert-butyldimethylsilyl chloride and imidazole gives 5'-O-(tert-butyldimethylsilyl)adenosine (II),which by reaction with 1,1'-thiocarbonyldiimidazole (III) in hot DMF is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-O-thionocarbonyladenosine (IV).The desulfurization of (IV) with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (V) or triethyl phosphite in THF yields 5'-O-(tert-butyldimethylsilyl)-2',3'-didehydro-2',3'-dideoxyadenosine (VI),which is deprotected with tetrabutylammonium fluoride in THF affording 2',3'-didehydro-2',3'-dideoxyadenosine (VII).Finally,this compound is hydrogenated with H2 over Pd/C in methanol.2) The reaction of silylated adenosine (II) with CS2 and NaOH in DMSO,followed by methylation with methyl iodide gives 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-[(methylthio)thiocarbonyl]ad enosine (VIII),which is desulfurized with tributyltin hydride and AIBN in refluxing toluene to yield the dideoxy-didehydroadenosine (VI),already obtained.
合成路线:3) The reaction of inosine (I) with tert-butyldimethylsilyl chloride by means of imidazole in DMF gives the 5'-O-silyl derivative (II),which by reaction with CS2 and 3-bromopropionitrile by means of NaOH in DMSO is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-(2-cyanoethyldithiocarbonyl)inosine (III).The reaction of (III) with tri-n-butyltin hydride and AIBN in refluxing toluene affords 5'-O-(tert-butyldimethylsilyl-2',3'-dideoxy-2',3'-didehydroinosine (IV),which is deprotected with tetrabutylammonium fluoride in THF to 2',3'-dideoxy-2',3'-didehydroinosine (V).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol - water.4) The reaction of (II) with 1,1'-thiocarbonyldiimidazole (DTI) in DMF gives 5'-O-(tert-butyldimethylsilyl)-2',3'-O-(thionocarbonyl)inosine (VI),which by reaction with refluxing triethyl phosphite is converted into the didehydro derivative (IV),already obtained (5).
参考文献标题:General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosides
文献作者:Chu,C.K.; Bhadti,V.S.; Doboszewski,B.; Gu,Z.P.; Kosugi,Y.; Pullaiah,K.C.; Van Roey,P.
参考来源:J Org Chem 1989,542217-25
合成路线:A new synthesis of 2',3'-dideoxyadenosine has been described:The stereospecific deamination - lactonization of L-glutamic acid (I) with NaNO2 - HCl in water gives (S)-(+)-gamma-carboxy-gamma-butyrolactone (II),which is esterified with ethanol - p-toluenesulfonic acid to the ester (III).The selective reduction of (III) with NaBH4 in ethanol yields (S)-(+)-gamma-(hydroxymethyl)-gamma-butyrolactone (IV),which is benzoylated with benzoyl chloride as usual,affording the benzoate (V).The selective reduction of (V) with disiamyl borane in THF gives the alcohol (VI),which is acetylated with acetic anhydride in pyridine to the acetate (VII).The reaction of (VII) with trimethylsilyl bromide in dichloromethane yields the tetrahydrofuryl bromide (VIII),which is condensed with the silylated adenine (IX) to afford 5'-O-benzoyl-2',3'-dideoxyadenosine (X).Finally,this compound is deprotected with NH3 in methanol.
合成路线:1) The stereospecific deamination - lactonization of L-glutamic acid (I) with NaNO2 - HCl in water gives (S)-(+)-gamma-carboxy-gamma-butyrolactone (II),which is esterified with ethanol and p-toluenesulfonic acid in the usual way,yielding the ethyl ester (III).The selective reduction of (III) with NaBH4 in ethanol affords (S)-(+)-gamma-(hydroxymethyl)-gamma-butyrolactone (IV),which is benzoylated with benzoyl chloride to the benzoate (V).The selective reduction of (V) with disiamyl borane in THF yields the alcohol (VI),which is acetylated with acetic anhydride in pyridine to the acetate (VII).The reaction of (VII) with trimethylsilyl bromide in dichloromethane affords the tetrahydrofuryl bromide (VIII),which is then condensed with the adenine (IX),giving 5'-O-benzoyl-2',3'-dideoxyadenosine (X).The deprotection of (X) with NH3 in methanol yields 2',3'-dideoxyadenosine,which is finally deaminated enzymatically with the enzyme adenosine deaminase.
参考文献标题:2',3'-dideoxynucleosides for AIDS chemotherapy
文献作者:Farina,V.; Benigni,D.A.
参考来源:Tetrahedron Lett 1988,29(11),1239-42
合成路线:3) The reaction of inosine (I) with tert-butyldimethylsilyl chloride by means of imidazole in DMF gives the 5'-O-silyl derivative (II),which by reaction with CS2 and 3-bromopropionitrile by means of NaOH in DMSO is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-(2-cyanoethyldithiocarbonyl)inosine (III).The reaction of (III) with tri-n-butyltin hydride and AIBN in refluxing toluene affords 5'-O-(tert-butyldimethylsilyl-2',3'-dideoxy-2',3'-didehydroinosine (IV),which is deprotected with tetrabutylammonium fluoride in THF to 2',3'-dideoxy-2',3'-didehydroinosine (V).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol - water.4) The reaction of (II) with 1,1'-thiocarbonyldiimidazole (DTI) in DMF gives 5'-O-(tert-butyldimethylsilyl)-2',3'-O-(thionocarbonyl)inosine (VI),which by reaction with refluxing triethyl phosphite is converted into the didehydro derivative (IV),already obtained (5).
参考文献标题:Synthesis of 2',3'-dideoxyinosine
文献作者:Webb,R.R.II,Wos,J.A.; Martin,J.C.; Brodfuehrer,P.R.
参考来源:Nucleosides Nucleotides 1988,7(2),147-53
合成路线:2) The reaction of uridine (I) with methyl orthoformate and p-toluenesulfonic acid gives the cyclic orthoester (II),which is acetylated with acetic anhydride at 100 C,yielding the 5'-acetoxy derivative (III).The reaction of (III) with acetic anhydride at temperatures over 120 C affords 5'-O-acetyl-2',3'-dideoxy-2',3'-didehydrouridine (IV),which is hydrogenated to 5'-O-acetyl-2',3'-dideoxyuridine (V).Hydrolysis of (V) affords 2',3'-dideoxyuridine (VI),which is finally submitted to a transdideoxyribosylation with hypoxanthine (VII) by incubation in an appropriate medium with Escherichia coli AJ 2595 resting cells.
参考文献标题:Production of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine from 2',3'-dideoxyuridine and the corresponding purine bases by resting cells of Escherichia coli AJ 2595
文献作者:Shirae,H.; Kobayashi,K.; Shiragami,H.; Irie,Y.; Yasuda,N.; Yokozeki,K.
参考来源:Appl Environ Microbiol 1989,55(2),419-24
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