Vinblastine → 4-Desacetylvinblastine

HRID 499966

反応式

HRID 499966 の反応式
[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C@:32]56[C@@H:36]7[C@:37]([CH2:52][CH3:53])([C@@H:41]([O:48]C(C)=O)[C@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@@H:31]5[N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[CH:38]=[CH:39][CH2:40][N:35]7[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1.CC[C@@]1(O)CN2C[C@H](C[C@](C(OC)=O)(C3C=C4[C@]56[C@@H]7[C@](CC)([C@@H](OC(C)=O)[C@](O)(C(OC)=O)[C@@H]5N(C)C4=CC=3OC)C=CCN7CC6)C3NC4C=CC=CC=4C=3CC2)C1.OS(O)(=O)=O>NN.C(O)C>[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C:32]56[C@@H:31]([N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[C@@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@H:41]([OH:48])[C@:37]3([CH2:52][CH3:53])[CH:38]=[CH:39][CH2:40][N:35]([C@H:36]53)[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1

参加物

4

反応物 2

HCID 13342VinblastineHCID 5388983Vinblastine Sulfate

生成物 1

HCID 1970264-Desacetylvinblastine

試薬・触媒・溶媒 1

HCID 129679701Hydrazine-ethanol溶媒

実験手順

Vinca alkaloids such as vinblastine can be conjugated directly to aldehyde-bearing linkers following conversion to a hydrazide form as described by Brady et al. (J. Med. Chem., 45:4706-4715, 2002). Briefly, vinblastine sulfate is dissolved in 1:1 hydrazine/ethanol and heated to 60° C.-65° C. for 22 hours to yield desacetylvinblastine 3-carboxhydrazide (Table 2, DAVCH). Alternatively, amine-reactive forms of vinblastine may be generated in situ as described by Trouet et al. (U.S. Pat. No. 4,870,162) by (1) initially converting vinblastine sulfate to the desacetyl form (e.g. as described by Brady et al., reacting with 1:3 hydrazine/methanol at 20° C. for 20 hours), (2) reacting the resulting free base with approximately 2-fold excess succinic anhydride to generate the hemisuccinate (Table 2, DAVS), and (3) reacting with isobutyl chloroformate to form the reactive mixed anhydride.

後処理

  1. temperatureheated to 60° C.-65° C. for 22 hours

出典と根拠

ORDレコード
ord-a46daf678c7e43fd939a5eee01069ad7
出典データセット
uspto-grants-2010_08
特許番号
US07767803B2

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