Camptothecin → 186669-19-2

HRID 1596747Notes

Reaction equation

HRID 1596747 reaction equation
[CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[BH4-].[Na+].I(O)(=O)(=O)=O.Br[CH2:35]C(OC(C)(C)C)=O.FC(F)(F)C([O-])=O>[Zn]>[CH3:1][CH2:2][C@:3]1([OH:26])[C:4]2[CH:25]=[C:24]3[N:12]([C:10](=[O:11])[C:5]=2[CH2:6][O:7][C:8](=[O:9])[CH2:35]1)[CH2:13][C:14]1[CH:15]=[C:16]2[C:21](=[N:22][C:23]3=1)[CH:20]=[CH:19][CH:18]=[CH:17]2

Participants

7

Reactant 5

HCID 24360CamptothecinHCID 65185Metaperiodic acidHCID 79177tert-Butyl bromoacetateHCID 84468TrifluoroacetateHCID 4311764Sodium borohydride

Product 1

HCID 10666346186669-19-2

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

is prepared according to the procedure of Bigg et al. (Bioorg. Med. Chem. Lett. 1997, 17, 2235-2238) by the reduction of camptothecin with sodium borohydride. This furnishes the hydroxylactol which converts to formyloxy-mappicin ketone using periodic acid. The reaction of this ketone with zinc and t-butyl bromoacetate followed treatment with trifluoroacetate affords homocamptothecin. To then derivitize homocamptothecin at the 12-position, a suspension of homocamptothecin (3.12 g, 8.6 mmol) in a mixture of chloroacetaldehyde (18 ml) and H2O (75 ml) is prepared. 75% H2SO4 (75 ml) is added dropwise, and then FeSO47H2O (2.40 g, 8.6 mmol) was added. To the ice-cold mixture, 30% H2O2 (15 ml, 6.6 mmol) is added dropwise for 2 h with stirring. The mixture is stirred at room temperature for 14 h and then diluted with H2O, extracted with chloroform (3×200 ml), and the organic layer washed with brine and dried over MgSO4. Evaporation of the solvent renders a brown oil which upon purification using column chromatography (eluent: chloroform: methanol 98:2) yields the yellow solid product.

Workup

  1. customis prepared
  2. customThis furnishes the hydroxylactol which

Sources & evidence

ORD record
ord-21251accc37a4911955cead18c50061b
Source dataset
uspto-grants-2001_09
Patent number
US06291676B1

Reaction notes

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