Sodium Hydroxide → Adriamycin aglycone

HRID 596935Notes

Reaction equation

HRID 596935 reaction equation
[CH3:1][C:2]([C@@:4]1([OH:29])[CH2:27][C@H:26]([OH:28])[C:7]2=[C:8]([OH:25])[C:9]3[C:21](=[O:22])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][C:19]=4[O:23][CH3:24])[C:13](=[O:14])[C:10]=3[C:11]([OH:12])=[C:6]2[CH2:5]1)=[O:3].BrBr.[OH-:32].[Na+]>C(Cl)(Cl)Cl>[CH3:24][O:23][C:19]1[C:20]2[C:21]([C:9]3[C:8]([OH:25])=[C:7]4[C:6]([CH2:5][C@@:4]([OH:29])([C:2]([CH2:1][OH:32])=[O:3])[CH2:27][C@@H:26]4[OH:28])=[C:11]([OH:12])[C:10]=3[C:13](=[O:14])[C:15]=2[CH:16]=[CH:17][CH:18]=1)=[O:22]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24408BromineHCID 83843(+)-Daunomycinone

Product 1

HCID 72401Adriamycin aglyconeYield 87%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

Daunomycinone (IX) (10 mg, 0.025 mmole) was placed in CHCl3 (1 ml). Br2 (13.5 mg) in CHCl3 (0.25 ml) was added and the solution stirred at 23° for 16 hrs. The solvent was removed and the residue was dissolved in 80% aq acetone (5 ml). NaOH (1.1 mg. 0.028 mmole) was added and the blue solution was refluxed for 5 min when the red color returned. The solution was concentrated to approximately 2 ml, diluted with water (10 ml) and extracted with 50% CHCl3 /MeOH (3 × 10 ml). The extracts were combined, dried and evaporated. The residue was crystallized from CHCl3 -MeOH/pet. ether (30°-60°) to afford 9.0 mg (87%) of (XI): irnujol 2.85 (OH), 5.75 (C = O), 615, 628 μ (chelated quinone); pmr 100 MHz CDCl3 δ 2.0-2.5 (m, 2H, 8-H2), 2.8-3.2 (m, 2H, 10-H2), 3.43 (m, 1H, 9-OH), 4.09 (s, 3H, OMe), 4.70 (d, 2H, J = 16Hz, 14-H2), 5.34 (m, 1H, ∥1/2 = 8Hz, 7-H), 7.38 (dd, 1H, J = 8Hz and J = 1Hz, 3-H), 7.76 (t, 1H, J = 8Hz, 2-H), 8.00 (dd, 1H, J = 8Hz and J = 1Hz, 1-H), 13.24 (s, 1H, 6-OH), 13.99 (s, 1H, 11-OH).

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in 80% aq acetone (5 ml)
  3. temperaturethe blue solution was refluxed for 5 min when the red color
  4. concentrationThe solution was concentrated to approximately 2 ml
  5. additiondiluted with water (10 ml)
  6. extractionextracted with 50% CHCl3 /MeOH (3 × 10 ml)
  7. customdried
  8. customevaporated
  9. customThe residue was crystallized from CHCl3 -MeOH/pet. ether (30°-60°)

Sources & evidence

ORD record
ord-9615eb7bd09f4645b7425247cb3d1b96
Source dataset
uspto-grants-1977_03
Patent number
US04012448

Reaction notes

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