合成路线:The regioselective reaction of cyclopentadiene (I) and sodium or commercial sodium cyclopentadienide (II) with benzyl chloromethyl ether (III) by means of the chiral catalyst (-)-diisopinocampheylborane in THF,followed by hydroxylation with H2O2/NaOH,gives (1S-trans)-2-(benzyloxymethyl)-3-cyclopenten-1-ol (IV),which is regioselectively epoxidized with tert-butyl hydroperoxide and vanadyl acetylacetonate in 2,2,4-trimethylpentane,yielding [1S-(1alpha,2alpha,3beta,5alpha)-2-(benzyloxymethyl)-6-oxabicyclo[3.1.0]hexan-3-ol (V).The protection of (V) with benzyl bromide and NaH affords the corresponding ether (VI),which is condensed with 6-O-benzylguanine (VII) by means of LiH in DMF to give the guanine derivative (VIII).The protection of the amino group of (VIII) with 4-methoxyphenyl(diphenyl)chloromethane (IX),TEA and DMAP in dichloromethane gives intermediate (X),which is oxidized at the free hydroxyl group with methylphosphonic acid,DCC and oxalic acid in DMSO or Dess Martin periodinane in dichloromethane,yielding the cyclopentanone derivative (XI).The reaction of (XI) with (i) Zn/TiCl4/CH2Br2 complex in THF/CH2Cl2,(ii) activated Zn/PbCl2/CH2I2/TiCl4 in THF/CH2Cl2 (2),(iii) Nysted reagent/TiCl4 in THF/CH2Cl2 or (iv) Tebbe reagent in toluene affords the corresponding methylene derivative (XII),which is partially deprotected with 3N HCl in hot THF,providing the dibenzylated compound (XI).Finally,this compound is treated with BCl3 in dichloromethane.(Scheme 18263401a)
参考文献标题:Improved process for preparing the antiviral agent [1S-(1alpha,3alpha,4beta)]-2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one
文献作者:Bisacchi,G.S.; Sundeen,J.E.(Bristol-Myers Squibb Co.)
参考来源:WO 9809964
合成路线:The regioselective reaction of cyclopentadiene (I) and sodium or commercial sodium cyclopentadienide (II) with benzyl chloromethyl ether (III) by means of the chiral catalyst (-)-diisopinocampheylborane in THF,followed by hydroxylation with H2O2/NaOH,gives (1S-trans)-2-(benzyloxymethyl)-3-cyclopenten-1-ol (IV),which is regioselectively epoxidized with tert-butyl hydroperoxide and vanadyl acetylacetonate in 2,2,4-trimethylpentane,yielding [1S-(1alpha,2alpha,3beta,5alpha)-2-(benzyloxymethyl)-6-oxabicyclo[3.1.0]hexan-3-ol (V).The protection of (V) with benzyl bromide and NaH affords the corresponding ether (VI),which is condensed with 6-O-benzylguanine (VII) by means of LiH in DMF to give the guanine derivative (VIII).The protection of the amino group of (VIII) with 4-methoxyphenyl(diphenyl)chloromethane (IX),TEA and DMAP in dichloromethane gives intermediate (X),which is oxidized at the free hydroxyl group with methylphosphonic acid,DCC and oxalic acid in DMSO or Dess Martin periodinane in dichloromethane,yielding the cyclopentanone derivative (XI).The reaction of (XI) with (i) Zn/TiCl4/CH2Br2 complex in THF/CH2Cl2,(ii) activated Zn/PbCl2/CH2I2/TiCl4 in THF/CH2Cl2 (2),(iii) Nysted reagent/TiCl4 in THF/CH2Cl2 or (iv) Tebbe reagent in toluene affords the corresponding methylene derivative (XII),which is partially deprotected with 3N HCl in hot THF,providing the dibenzylated compound (XI).Finally,this compound is treated with BCl3 in dichloromethane.(Scheme 18263401a)
参考文献标题:BMS-200475.A novel carbocyclic 2'-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro
文献作者:Bisacchi,G.S.; Chao,S.T.; Bachard,C.; et al.
参考来源:Bioorg Med Chem Lett 1997,7(2),127
合成路线:The regioselective reaction of cyclopentadiene (I) and sodium or commercial sodium cyclopentadienide (II) with benzyl chloromethyl ether (III) by means of the chiral catalyst (-)-diisopinocampheylborane in THF,followed by hydroxylation with H2O2/NaOH,gives (1S-trans)-2-(benzyloxymethyl)-3-cyclopenten-1-ol (IV),which is regioselectively epoxidized with tert-butyl hydroperoxide and vanadyl acetylacetonate in 2,2,4-trimethylpentane,yielding [1S-(1alpha,2alpha,3beta,5alpha)-2-(benzyloxymethyl)-6-oxabicyclo[3.1.0]hexan-3-ol (V).The protection of (V) with benzyl bromide and NaH affords the corresponding ether (VI),which is condensed with 6-O-benzylguanine (VII) by means of LiH in DMF to give the guanine derivative (VIII).The protection of the amino group of (VIII) with 4-methoxyphenyl(diphenyl)chloromethane (IX),TEA and DMAP in dichloromethane gives intermediate (X),which is oxidized at the free hydroxyl group with methylphosphonic acid,DCC and oxalic acid in DMSO or Dess Martin periodinane in dichloromethane,yielding the cyclopentanone derivative (XI).The reaction of (XI) with (i) Zn/TiCl4/CH2Br2 complex in THF/CH2Cl2,(ii) activated Zn/PbCl2/CH2I2/TiCl4 in THF/CH2Cl2 (2),(iii) Nysted reagent/TiCl4 in THF/CH2Cl2 or (iv) Tebbe reagent in toluene affords the corresponding methylene derivative (XII),which is partially deprotected with 3N HCl in hot THF,providing the dibenzylated compound (XI).Finally,this compound is treated with BCl3 in dichloromethane.(Scheme 18263401a)
参考文献标题:BMS-200475
文献作者:Castar,J.; Graul,A.
参考来源:Drugs Fut 1999,24(111),1173
产品链接: CAS No. 142217-69-4›› 产品链接: CAS No.209216-23-9››