Reaction #1255289

ord-0556b18caacc48569f6c73034aafdb9d

Reaction equation

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin HCl
→
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin

Reactants

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin HCl
—
hydrazone

Reagents

None

Solvents

CN(C)C=O
dimethylformamide

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.DISSOLUTIONAfter dissolving

Procedure

After dissolving 0.25 g of hydrazone linker-bound mPEG-PLGA obtained in Example 3 and 10 mg of doxorubicin-HCl in 7.5 ml of dimethylformamide, conjugation reaction was performed for 24 hours at room temperature under nitrogen gas to obtain doxorubicin-conjugated micelle monomers. The micelle monomers were dispersed in 300 ml of triple distilled water to form doxorubicin-conjugated sustained release micelles, and free doxorubicin was removed by dialyzing the mixture 5 times against 3 L of triple distilled water each time. Doxorubicin-conjugated sustained release micelles were pelletized by ultracentrifugation, and freeze-dried after removing supernatant, and then, stored in the form of doxorubicin-conjugated micelle monomers. The efficiency of conjugation of doxorubicin was determined analogously as in Example 2(see: Table 3 below).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06623729B2uspto-grants-2003_09