Lipoic acid → HCID 131731047, compound

HRID 2043386Notes

Reaction equation

HRID 2043386 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].[CH2:63]1[C@@H:67]([CH2:68][CH2:69][CH2:70][CH2:71][C:72]([OH:74])=[O:73])[S:66][S:65][CH2:64]1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[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].[CH2:63]1[C@@H:67]([CH2:68][CH2:69][CH2:70][CH2:71][C:72]([OH:74])=[O:73])[S:66][S:65][CH2:64]1

Participants

6

Reactant 3

HCID 6112Lipoic acid3×HCID 10868DicyclohexylcarbodiimideHCID 36314Paclitaxel3×

Product 1

HCID 131731047HCID 131731047, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Paclitaxel-lipoate was synthesized from paclitaxel (Farmachem, Lugano, Switzerland) and lipoic acid (Sigma, St. Louis, Mo., USA) in a single step that coupled lipoate to paclitaxel at the 2′-hydroxyl position. To a solution of paclitaxel (35 mg; 41 μmmol) in dry methylene chloride (2.5 ml) under nitrogen were added 4-dimethylaminopyridine (5 mg; 41 μmmol), 1, 3-dicyclohexylcarbodiimide (16.9 mg; 82 μmmol), and lipoic acid (8.5 mg; 41 μmol). The reaction mixture was stirred at ambient temperature for 2 h. After dilution with diethyl ether, the reaction mixture was washed with 5% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride. The mixture was dried (sodium sulfate) and concentrated. Radial chromatography (silica gel; ethyl acetate-hexane 1:1) of the residue gave 45 mg (90%) of solid paclitaxel-lipoate. The product was analysed using LC-MS as shown in FIG. 3 and H-NMR as shown in FIG. 4.

Workup

  1. washAfter dilution with diethyl ether, the reaction mixture was washed with 5% aqueous hydrochloric acid, water, and saturated aqueous sodium chloride
  2. dry with materialThe mixture was dried (sodium sulfate)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-22bd151d64a341a58bd237c65fab4e73
Source dataset
uspto-grants-2013_11
Patent number
US08586625B2

Reaction notes

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