10-deacetylbaccatin III → Paclitaxel

HRID 1769405

Reaction equation

HRID 1769405 reaction equation
[CH3:1][C:2]1[C@@H](O)C[C@]2(O)C(C)(C)C=1[C@@H](O)C([C@@]1(C)[C@H]([C@@H]2OC(C2C=CC=CC=2)=O)[C@]2(OC(C)=O)CO[C@@H]2C[C@@H]1O)=O.[CH3:40]/[CH:41]=[C:42](/[C:44]([NH:46][C@H:47]([C@@H:54]([OH:99])[C:55]([O:57][C@@H:58]1[C:79]([CH3:80])=[C:78]2[C:81]([CH3:83])([CH3:82])[C@:60]([OH:98])([C@@H:61]([O:89][C:90]([C:92]3[CH:93]=[CH:94][CH:95]=[CH:96][CH:97]=3)=[O:91])[C@@H:62]3[C@:67]4([O:70][C:71]([CH3:73])=[O:72])[CH2:68][O:69][C@@H:66]4[CH2:65][C@H:64]([OH:74])[C@@:63]3([CH3:88])[C:75]([C@@H:77]2[O:84][C:85]([CH3:87])=[O:86])=[O:76])[CH2:59]1)=[O:56])[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)=[O:45])\[CH3:43]>>[CH3:80][C:79]1[C@@H:58]([O:57][C:55]([C@H:54]([OH:99])[C@@H:47]([NH:46][C:44]([C:42]2[CH:43]=[CH:1][CH:2]=[CH:40][CH:41]=2)=[O:45])[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:56])[CH2:59][C@:60]2([OH:98])[C:81]([CH3:82])([CH3:83])[C:78]=1[C@@H:77]([O:84][C:85]([CH3:87])=[O:86])[C:75]([C@@:63]1([CH3:88])[C@H:62]([C@@H:61]2[O:89][C:90]([C:92]2[CH:93]=[CH:94][CH:95]=[CH:96][CH:97]=2)=[O:91])[C@:67]2([O:70][C:71]([CH3:73])=[O:72])[CH2:68][O:69][C@@H:66]2[CH2:65][C@@H:64]1[OH:74])=[O:76]

Participants

3

Reactant 2

HCID 15427210-deacetylbaccatin IIIHCID 6436208Cephalomannine

Product 1

HCID 36314PaclitaxelYield 0.01%

Procedure

The solid was chromatographed as described under Example 1 except that RPLC C8 silica (100 g) was used in methanol/water 20%. A pressure of 50 psi was used to obtain an adequate rate. One hundred fifty fractions of 10 ml were collected, while a gradient of 25, 35, 45, 55 and 65% methanol in water was being used. The fractions were monitored as before and fractions containing 10-deacetylbaccatin III (fractions 25-35), brevitaxane A (fractions 60-90), cephalomannine (fractions 120-125) and taxol (fractions 135-150) were combined separately, concentrated to dryness and recrystallized from chloroform/hexane (1:1) to give the pure compounds. 10-deacetylbaccatin III, brevitaxane A, 2.0 g (0.2% yield, based on plant material), cephalomannine, 0.03 g (0.003% yield, based on plant material) and taxol 0.1 g (0.01% yield, based on plant material).

Workup

  1. customThe solid was chromatographed
  2. customto obtain an adequate rate
  3. customOne hundred fifty fractions of 10 ml were collected, while a gradient of 25, 35, 45, 55 and 65% methanol in water
  4. additioncontaining 10-deacetylbaccatin III (fractions 25-35), brevitaxane A (fractions 60-90), cephalomannine (fractions 120-125) and taxol (fractions 135-150)
  5. concentrationconcentrated to dryness
  6. customrecrystallized from chloroform/hexane (1:1)
  7. customto give the pure compounds

Sources & evidence

ORD record
ord-d8019e3e10844da28619272a7d3974dc
Source dataset
uspto-grants-1995_01
Patent number
US05380916

Linked notes

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