Water → Dibekacin

HRID 1578680Notes

Reaction equation

HRID 1578680 reaction equation
[CH2:1]1[C@H:6]([NH2:7])[C@@H:5]([O:8][C@H:9]2[O:14][C@H:13]([CH2:15][NH2:16])[C@@H:12](O)[C@H:11](O)[C@H:10]2O)[C@H:4]([OH:20])[C@@H:3]([O:21][C@H:22]2[O:27][C@H:26]([CH2:28][OH:29])[C@@H:25]([OH:30])[C@H:24]([NH2:31])[C@H:23]2[OH:32])[C@@H:2]1[NH2:33].O.C([N:37](CC)CC)C.C(OC(N=[N+]=[N-])=O)(C)(C)C>N1C=CC=CC=1>[CH2:12]1[C@@H:13]([CH2:15][NH2:16])[O:14][C@H:9]([O:8][C@H:5]2[C@H:4]([OH:20])[C@@H:3]([O:21][C@H:22]3[O:27][C@H:26]([CH2:28][OH:29])[C@@H:25]([OH:30])[C@H:24]([NH2:31])[C@H:23]3[OH:32])[C@H:2]([NH2:33])[CH2:1][C@@H:6]2[NH2:7])[C@H:10]([NH2:37])[CH2:11]1

Participants

6

Reactant 4

HCID 962WaterHCID 6032KanamycinHCID 8471TriethylamineHCID 61256Carbonazidic acid, 1,1-dimethylethyl ester2×

Product 1

HCID 470999Dibekacin

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

For instance, 6'-N-t-butoxycarbonylkanamycin may be prepared in a high yield by reacting kanamycin in solution in a mixture of pyridine, water and triethylamine with a 1 to 3 molar proportion of t-butoxycarbonyl azide added dropwise thereto under agitation, stirring the admixture at ambient temperature overnight, concentrating the reaction mixture to dryness in vacuo and then purifying the solid residue in a column chromatography with a cation-exchange resin such as Amberlite CG 50 (NH4 form), while recovering the unreacted kanamycin. Moreover, 2',6'-di-N-t-butoxycarbonylkanamycin B or 3',4'-dideoxykanamycin B may be prepared in a high yield, for example, by reacting kanamycin B or 3',4'-dideoxykanamycin B in solution in a mixture of pyridine, water and triethylamine with a 2-3 molar proportion of t-butoxycarbonyl azide added dropwise thereto under agitation, stirring the admixture at ambient temperature overnight, concentrating the reaction mixture to dryness in vacuo, and then purifying the solid residue in column chromatography with a cation-exchange resin such as Amberlite CG 50 (NH4 form). When this preparation procedure is repeated with 2 molar proportions or less of t-butoxycarbonyl azide, there may be obtained 6'-N-t-butoxycarbonyl-kanamycin B or 3',4'-dideoxykanamycin B in a high yield. 6'-N-t-butoxycarbonyl-kanamycin B or 3',4'-dideoxykanamycin B once isolated may also be converted into the 2',6'-di-N-t-butoxycarbonyl derivative by further reacting with 1 to 2 molar proportions of t-butoxycarbonyl azide in a similar manner. The compounds of the formula (IV) prepared in the above procedures may be employed as a starting compound in the process of this invention without purification.

Workup

  1. customFor instance, 6'-N-t-butoxycarbonylkanamycin may be prepared in
  2. customa high yield
  3. additionadded dropwise
  4. concentrationconcentrating the reaction mixture to dryness in vacuo
  5. custompurifying the solid residue in a column chromatography with a cation-exchange resin such as Amberlite CG 50 (NH4 form)
  6. customwhile recovering the unreacted kanamycin
  7. additionin a mixture of pyridine, water and triethylamine with a 2-3 molar proportion of t-butoxycarbonyl azide
  8. additionadded dropwise
  9. stirringunder agitation, stirring the admixture at ambient temperature overnight
  10. concentrationconcentrating the reaction mixture to dryness in vacuo
  11. custompurifying the solid residue in column chromatography with a cation-exchange resin such as Amberlite CG 50 (NH4 form)
  12. customWhen this preparation procedure

Sources & evidence

ORD record
ord-230e727b16eb4c3bbf2f656e48142abd
Source dataset
uspto-grants-1976_02
Patent number
US03939143

Reaction notes

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