合成路线:The hydrolysis of the diacetyl derivative (I) with Ba(OH)2 in refluxing water gives the amino alcohol (II),which is condensed with 4,6-dichloro-2-aminopyrimidine (III) by means of TEA in refluxing tert-butanol to yield the adduct (IV).The condensation of (IV) with the diazonium salt (V) affords the azo compound (VI),which is reduced with Zn/HOAc to provide the diamine (VII).The cyclization of (VII) with triethyl orthoformate gives the 6-chloropurine derivative (VIII),which is finally treated with NaOH in refluxing water to afford the target guanine derivative as a racemic compound.
参考文献标题:Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides
文献作者:Hua,M.; Vince,R.
参考来源:J Med Chem 1990,33(1),17-21
合成路线:The reaction of 14C-labeled cyanhydric acid (I) with HCl and ethanol gives the iminoester (II),which by reaction with more ethanol in chloroform yields the labeled orthoester (III).The cyclization of the triaminopyrimidinone (IV) with orthoester (III) by means of Ms-OH in chloroform affords the chloropurine derivative (V),which is finally hydrolyzed with NaOH to afford the target compound,the 14C-labeled carbovir.
参考文献标题:Synthesis of carbon-14 labelled cis-2-amino-1,9-dihydro-9-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-H6-purine-6-one; [8-14C]carbovir: A promising anti-AIDS drug
文献作者:Gopinathan,M.B.; Kepler,J.A.
参考来源:J Label Compd Radiopharm 1991,29(6),645
合成路线:The selective silylation of (-)-aristeromycin (I) with Hdms-Cl and imidazole gives the monosilyl ether (II),which is treated with thiocarbonyl dimidazole (TCDI) in hot ethyl acetate to yield the cyclic thiocarbonate (III).The reaction of (III) with 1,3-dimethyl-1,3,2-diazaphospholidine (DMPDP) in refluxing THF affords the desired cyclopentene derivative (IV).In an alternative method,the reaction of (II) with methyl orthoformate provides the cyclic orthoester (V),which undergoes thermal elimination with acetic acid at high temperature giving the desired cyclopentene derivative (IV).The oxidation of (IV) with MCPBA in chloroform yields the N-oxide (VI),which by reaction with Br-CN in methanol affords the oxadiazole derivative (VII).The cleavage of the oxadiazole ring of (VII) and simultaneous methylation with TEA and Me-I provided the cyanoimino derivative (VIII),which is submitted to a Dimroth rearrangement by means of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in refluxing aqueous ethanol to give the methoxylated diaminopurine (IX).The reductive cleavage of the methoxyamino group of (IX) with Al/Hg in aqueous THF yields the silylated diaminopurine (X),which is deprotected with HCl in ethanol to afford the free diaminopurine precursor (XI).Finally,this compound is enzymatically deaminated by means of adenosine deaminase to furnish the target (-)-carbovir.
参考文献标题:Synthesis from (-)-aristeromycin and x-ray structure of (-)-carbovir
文献作者:Exall,A.M.; et al.
参考来源:J Chem Soc - Perkins Trans I 1991,(10),2467
合成路线:The protection of the chiral epoxy-alcohol (I) with Pmb-Cl,NaH and tetrabutylammonium iodide (TBAI) gives the protected compound (II),which is condensed with 2-amino-6-(2-methoxyethoxy)purine (III) in hot DMF to yield the adduct (IV).Elimination of the OH group of (IV) by means of a treatment with phenyl chlorothioformate,followed by a thermal elimination reaction with Bu3SnH and AIBN,affords the carbocyclic purine (V).The selective deprotection of (V) with DDQ in dichloromethane provides the cyclopentanol derivative (VI),which is treated with MsCl and DMAP to give the mesylate (VII).The reaction of (VII) with sodium 2-methoxyethanolate (A) in DMF yields the cyclopentene derivative (VIII),which is treated with AlI3 in hot acetonitrile to afford the carbocyclic guanine derivative (IX).The deprotection of (X) with BF3/Et2O and Ac2O provides the diacetyl derivative (X),which is finally deacetylated to the target chiral compound by means of NH3 in methanol.
合成路线:The reaction of the chiral epoxy-alcohol (I) with MsCl,TEA and DMAP gives the mesylate (II),which is treated with TBAF in THF to yield the unsaturated epoxide (III).The condensation of (III) with diaminopurine (IV) by means of NaH in DMF affords the carbocyclic purine (V),which is dehydroxylated by reaction with phenyl chlorothioformate,followed by a thermal elimination reaction with Bu3SnH and AIBN to provide the carbocyclic purine (VI).The debenzylation of (VI) by means of BF3/Et2O and Ac2O gives the diacetyl derivative (VII),which is selectively O-deacetylated with NH3 in methanol,yielding 2-acetamido-6-aminopurine (VIII).The reaction of (VIII) with NaNO2 and acetic acid affords the N-acetylated guanine derivative (IX),which is finally treated with NH3 in methanol to provide the target compound.
参考文献标题:Total synthesis of (-)-carbovir
文献作者:Jones,M.F.; et al.
参考来源:J Chem Soc - Perkins Trans I 1991,(10),2479
合成路线:The hydrolysis of the chiral unsaturated bicyclic lactam (I) with aqueous refluxing HCl gives the amino acid (II),which is esterified with 2,2-dimethoxypropane,methanol and HCl to yield the methyl ester (III).The acylation of (III) with Ac2O and pyridine in dichloromethane affords the acetamide (IV),which is reduced with calcium borohydride in THF,providing the carbinol (V).The hydrolysis of the amido group of (V) with HCl in refluxing ethanol/water gives the chiral amino alcohol (VI),which is condensed with 2-amino-4,6-dichloropyrimidine (VII) by means of DIEA in refluxing butanol,yielding the adduct (VIII).The reaction of (VIII) with 4-chlorophenyldiazonium chloride (IX) by means of HOAc and NaOAc in water affords the azo compound (X),which is reduced with Zn and HOAc to provide the triaminopyrimidine (XI).The cyclization of (XI) with triethyl orthoformate gives the carbocyclic chloropurine (XII),which is finally treated with NaOH in refluxing water to yield the target carbocyclic guanine.
参考文献标题:Potential use of carbocyclic nucleosides for the treatment of AIDS - Chemo-enzymatic syntheses of the enantiomers of carbovir
文献作者:Evans,C.T.; et al.
参考来源:J Chem Soc - Perkins Trans I 1992,(5),589
合成路线:The addition of HCl to cyclopentadiene (I) gives 3-chlorocyclopentene (II),which is converted to racemic 2-cyclopentene-1-carboxylic acid (III).Optical resolution of (II) by crystallization of its (-)-1-phenylethylamine yields the desired enantiomer (IV),which is reduced with LiAlH4 in ethyl ether affording the chiral carbinol (V) (ee 98%).The reaction of (V) successively with BuLi,CO2 and I2 provides the iodinated cyclic carbonate (VI),which is treated with DBU in hot toluene to give the unsaturated cyclic carbonate (VII).The condensation of (VII) with 2-amino-6-chloropurine (VIII) by means of a Pd catalyst yields the carbocyclic purine (IX),which is finally hydrolyzed with aqueous NaOH to afford the target carbocyclic guanine.Alternatively,carbinol (V) can also be obtained by the vitamin B12/Zn/NH4Cl-catalyzed isomerization of 1,2-epoxycyclopentane (X) to the chiral cyclopentenol (XI),which by a [2,3]-sigmatropic Wittig rearrangement with KH,ICH2-SnBu4 and BuLi yields the target carbinol (V).However,the enantiomeric excess obtained is only ee 54%.
参考文献标题:A short synthesis of (-)-carbovir
文献作者:Hildbrand,S.; et al.
参考来源:Helv Chim Acta 1994,77(5),1236
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