Erythromycin → Erythromycin A enol ether

HRID 2111513Notes

Reaction equation

HRID 2111513 reaction equation
CC[C@@H](O)[C@@](O)([C@@H]1OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@@](OC)(C)C2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@]2(C)OC(=C(C)C2)[C@@H]1C)C.[CH3:51][CH2:52][C@H:53]1[O:68][C:66](=[O:67])[C@H:65]([CH3:69])[C@@H:64]([O:70][C@@H:71]2[O:76][C@@H:75]([CH3:77])[C@H:74]([OH:78])[C@@:73]([O:80][CH3:81])([CH3:79])[CH2:72]2)[C@H:63]([CH3:82])[C@@H:62]([O:83][C@@H:84]2[O:89][C@H:88]([CH3:90])[CH2:87][C@H:86]([N:91]([CH3:93])[CH3:92])[C@H:85]2[OH:94])[C@@:61](O)([CH3:95])[CH2:60][C@@H:59]([CH3:97])[C:57](=[O:58])[C@H:56]([CH3:98])[C@@H:55]([OH:99])[C@@:54]1([OH:101])[CH3:100].C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH3:51][CH2:52][C@H:53]1[O:68][C:66](=[O:67])[C@H:65]([CH3:69])[C@@H:64]([O:70][C@@H:71]2[O:76][C@@H:75]([CH3:77])[C@H:74]([OH:78])[C@@:73]([O:80][CH3:81])([CH3:79])[CH2:72]2)[C@H:63]([CH3:82])[C@@H:62]([O:83][C@@H:84]2[O:89][C@H:88]([CH3:90])[CH2:87][C@H:86]([N:91]([CH3:92])[CH3:93])[C@H:85]2[OH:94])[C@:61]2([CH3:95])[O:58][C:57](=[C:59]([CH3:97])[CH2:60]2)[C@H:56]([CH3:98])[C@@H:55]([OH:99])[C@@:54]1([OH:101])[CH3:100]

Participants

5

Reactant 3

HCID 12560ErythromycinHCID 516892Sodium BicarbonateHCID 9875064LY 267108

Product 1

HCID 83954Erythromycin A enol ether

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Synthesis of EM701 was disclosed in detail in WO 02/14338 A1. A glacial acetic acid solution of erythromycin was stirred at room temperature for 2 hours, and aqueous sodium hydrogencarbonate solution was slowly added and neutralized. The reaction mixture was extracted with chloroform. The organic layer was dehydrated by adding anhydrous sodium sulfate, which was removed off by filtration to obtain crude product. The crude product was purified by silica gel column chromatography with chloroform-methanol-aqueous ammonia (10:0.5:0.01→10:1:0.05) to obtain erythromycin A enol ether. Potassium carbonate was added to methanol solution of erythromycin A enol ether and refluxed for 2 hours. After solvent was removed, the residue was dissolved in aqueous sodium hydrogencarbonate and the mixture was extracted with chloroform. The extract was dehydrated with sodium sulfate, filtered and distilled off. The obtained crude product was purified by silica gel column chromatography with chloroform-methanol-aqueous ammonia (10:0.5:0.01→10:1:0.05) to obtain EM701 (white powder).

Workup

  1. extractionThe reaction mixture was extracted with chloroform
  2. additionby adding anhydrous sodium sulfate, which
  3. customwas removed off by filtration
  4. customto obtain crude product
  5. customThe crude product was purified by silica gel column chromatography with chloroform-methanol-aqueous ammonia (10:0.5:0.01→10:1:0.05)

Sources & evidence

ORD record
ord-20f04dbbc9e74f7280d839e3ca439e37
Source dataset
uspto-grants-2009_04
Patent number
US07521428B2

Reaction notes

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