Methyl p-toluenesulfonate → Methylamphotericin B

HRID 1602584Notes

Reaction equation

HRID 1602584 reaction equation
Cl[C:2]1C=CC(C=O)=CC=1.[CH3:10][C@@H:11]1[C@@H:50]([OH:51])[C@@H:49]([CH3:52])[C@H:48]([CH3:53])[O:47][C:45](=[O:46])[CH2:44][C@H:43]([OH:54])[CH2:42][C@H:41]([OH:55])[CH2:40][CH2:39][C@@H:38]([OH:56])[C@H:37]([OH:57])[CH2:36][C@H:35]([OH:58])[CH2:34][C@@:32]2([OH:59])[O:33][C@H:28]([C@H:29]([C:61]([OH:63])=[O:62])[C@@H:30]([OH:60])[CH2:31]2)[CH2:27][C@@H:26]([O:64][C@@H:65]2[O:70][C@H:69]([CH3:71])[C@@H:68]([OH:72])[C@H:67]([NH2:73])[C@@H:66]2[OH:74])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=[CH:12]1.C(N(CC)C(C)C)(C)C.C1(C)C=CC(S(OC)(=O)=O)=CC=1>CN(C=O)C>[CH3:10][C@@H:11]1[C@@H:50]([OH:51])[C@@H:49]([CH3:52])[C@H:48]([CH3:53])[O:47][C:45](=[O:46])[CH2:44][C@H:43]([OH:54])[CH2:42][C@H:41]([OH:55])[CH2:40][CH2:39][C@@H:38]([OH:56])[C@H:37]([OH:57])[CH2:36][C@H:35]([OH:58])[CH2:34][C@@:32]2([OH:59])[O:33][C@H:28]([C@H:29]([C:61]([O:63][CH3:2])=[O:62])[C@@H:30]([OH:60])[CH2:31]2)[CH2:27][C@@H:26]([O:64][C@@H:65]2[O:70][C@H:69]([CH3:71])[C@@H:68]([OH:72])[C@H:67]([NH2:73])[C@@H:66]2[OH:74])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=[CH:12]1

Participants

6

Reactant 4

HCID 6645Methyl p-toluenesulfonateHCID 77264-ChlorobenzaldehydeHCID 81531DiisopropylethylamineHCID 5280965Amphotericin B

Product 1

HCID 11968030Methylamphotericin BYield 0%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 1.5 mL of anhydrous DMF in a 3 mL flask was added p-chlorobenzaldehyde (0.0663 g, 4.72×E-4 moles). While purging the flask with nitrogen, Amphotericin B (0.1511 g, 1.51×E-4 moles) is slowly sifted into the vigorously stirred solution over 3 to 4 minutes. All the solid dissolved within 15 minutes and stirring was continued for an additional 30 minutes. At this point all the Amphotericin B was converted to the soluble N-p-chlorobenzylidine derivative. To the clear yellow solution was added N,N-diisopropylethylamine (0.079 mL, 4.53×E-4 moles) followed by methyl p-toluenesulfonate (0.0843 g, 4.53×E-4 moles). The reaction mixture was allowed to stir for 22 hours at ambient temperature and a small aliquot of the reaction mixture was removed and analyzed by reverse phase HPLC. The analysis indicated no unreacted Amphotericin B was present in the reaction mixture. The major component of the product mixture was Amphotericin B methyl ester. The mixture was added to 15 mL of methyl tert.-butyl ether and a yellow solid precipitated. The solid was separated by centrifugation and washed once with 10 mL of methyl tert.-butyl ether. Drying under high vacuum afforded 0.184 g of p-chlorobenzylidine Amphotericin B methyl ester.

Workup

  1. filtrationis slowly sifted into the vigorously stirred solution over 3 to 4 minutes
  2. dissolutionAll the solid dissolved within 15 minutes
  3. stirringto stir for 22 hours at ambient temperature
  4. customa small aliquot of the reaction mixture was removed
  5. additionThe mixture was added to 15 mL of methyl tert.-butyl ether
  6. customa yellow solid precipitated
  7. customThe solid was separated by centrifugation
  8. washwashed once with 10 mL of methyl tert.-butyl ether
  9. customDrying under high vacuum

Sources & evidence

ORD record
ord-58a99a4ec4e34a3cba50e0b8203f883b
Source dataset
uspto-grants-1999_11
Patent number
US05981721

Reaction notes

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