Paclitaxel → Fmoc-Leu PABC Paclitaxel

HRID 237415

Reaction equation

HRID 237415 reaction equation
[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:40])[C@@H:24]([NH:31][C:32]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6].[NH:63]([C:72]([O:74][CH2:75][CH:76]1[C:88]2[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=2)[C:82]2[C:77]1=[CH:78][CH:79]=[CH:80][CH:81]=2)=[O:73])[C@H:64]([C:69]([OH:71])=[O:70])[CH2:65][CH:66]([CH3:68])[CH3:67].[CH3:89][C:90]([NH:101][CH2:102][CH:103]([OH:119])[CH2:104][O:105][C:106]1[C:111]2[C:112]3[C:117]([NH:118][C:110]=2[CH:109]=[CH:108][CH:107]=1)=[CH:116][CH:115]=[CH:114][CH:113]=3)([C:92]1[CH:97]=[CH:96][C:95]([N:98]=[N+:99]=[N-:100])=[CH:94][CH:93]=1)[CH3:91]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[NH:63]([C:72]([O:74][CH2:75][CH:76]1[C:77]2[C:82](=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:83]2[C:88]1=[CH:87][CH:86]=[CH:85][CH:84]=2)=[O:73])[C@H:64]([C:69]([OH:71])=[O:70])[CH2:65][CH:66]([CH3:68])[CH3:67].[CH3:91][C:90]([NH:101][CH2:102][CH:103]([OH:119])[CH2:104][O:105][C:106]1[C:111]2[C:112]3[C:117]([NH:118][C:110]=2[CH:109]=[CH:108][CH:107]=1)=[CH:116][CH:115]=[CH:114][CH:113]=3)([C:92]1[CH:97]=[CH:96][C:95]([N:98]=[N+:99]=[N-:100])=[CH:94][CH:93]=1)[CH3:89].[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:40])[C@@H:24]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6]

Participants

5

Reactant 2

HCID 36314PaclitaxelHCID 131731174Fmoc-Leu PABC

Product 1

HCID 131731173Fmoc-Leu PABC PaclitaxelYield 93%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Paclitaxel (0.37 g, 0.44 mmol) and 4-Dimethylaminopyridine (DMAP) (0.05 g, 0.44 mmol) were added to a solution of 7 (0.27 g, 0.44 mmol) in anhydrous DCM (15 mL), and the reaction was stirred in the dark at room temperature for 24 hours. Subsequently, DCM (20 mL) was added and the reaction mixture was extracted with NaHCO3, brine and dried over sodium sulphate. The residue was purified on a silica gel column using ethyl acetate/hexane (1:1) to afford 8 (550 mg, 93%) as a white powder. ESI-MS (5 kV, MeOH): m/z (%)=1360.1 (100) [M+Na]+; HPLC (230 nm): >95%.

Workup

  1. extractionthe reaction mixture was extracted with NaHCO3, brine
  2. dry with materialdried over sodium sulphate
  3. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-baa64055c72c46edb4b6fb547eebad34
Source dataset
uspto-grants-2014_02
Patent number
US08642555B2

Linked notes

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