Dicyclohexylcarbodiimide → Maytansine

HRID 734163ノート

反応式

HRID 734163 の反応式
[CH3:1][N:2]([C:8](=[O:14])[CH2:9]CSSC)[C@H:3]([C:5]([OH:7])=[O:6])[CH3:4].C1(N=C=NC2CCCCC2)CCCCC1.[CH3:30][CH:31]1[CH:56]2[O:57][C:55]2([CH3:58])[CH:54](O)[CH2:53][C:51](=[O:52])[N:50]([CH3:60])[C:43]2=[C:44]([Cl:49])[C:45]([O:47][CH3:48])=[CH:46][C:41](=[CH:42]2)[CH2:40][C:39]([CH3:61])=[CH:38][CH:37]=[CH:36][CH:35]([O:62][CH3:63])[C:34]2([OH:68])[NH:64][C:65]([O:67][CH:32]1[CH2:33]2)=[O:66]>C(Cl)Cl.[Cl-].[Zn+2].[Cl-]>[CH3:30][C@H:31]1[C@@H:56]2[O:57][C@@:55]2([CH3:58])[C@@H:54]([O:7][C:5]([C@@H:3]([N:2]([C:8]([CH3:9])=[O:14])[CH3:1])[CH3:4])=[O:6])[CH2:53][C:51](=[O:52])[N:50]([CH3:60])[C:43]2=[C:44]([Cl:49])[C:45]([O:47][CH3:48])=[CH:46][C:41](=[CH:42]2)[CH2:40][C:39]([CH3:61])=[CH:38][CH:37]=[CH:36][C@@H:35]([O:62][CH3:63])[C@:34]2([OH:68])[NH:64][C:65]([O:67][C@H:32]1[CH2:33]2)=[O:66]

参加物

6

反応物 3

HCID 10868DicyclohexylcarbodiimideHCID 5358230HCID 5358230、化合物HCID 9942784HCID 9942784、化合物

生成物 1

HCID 5281828Maytansine収率 17.3%

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒2 回HCID 6344Dichloromethane溶媒2 回

実験手順

N-methyl-N-(methyl dithiopropanoyl)-L-alanine (26 mg) prepared by a different process in accordance with a reference was dissolved in 3 ml of CH2Cl2, 30 mg of dicyclohexylcarbodiimide (2 equivalent amounts) and 20 μl of 1M zinc chloride (1 equivalent amount) were added thereto, and the mixture was stirred at room temperature for 30 minutes. Since the reaction did not proceed under this condition, the amount of 1M zinc chloride added was changed to 100 μl (5 equivalent amounts), and the mixture was stirred at room temperature for 30 minutes. A solution of 11.8 mg of maytansinol in 1 ml of CH2Cl2 was added thereto for esterification. The reaction solution was concentrated to dryness 3 hours later, the main product was purified by preparative TLC (CH2Cl2:MeOH=10:1) and then by preparative HPLC (ODS column, eluent: 60% CH3CN). As a result, 2.5 mg of maytansine derivative (May-SS-Me) was obtained. FIG. 6 shows the resulting May-SS-Me by 500 MHz 1H NMR. In the test for assaying the cellular cytotoxicity of the human myeloma cell strain IM9 as described in Example 19, IC50 of the obtained May-SS-Me was 10 nM, which was 1/1000 or less than that of ansamitocin P-3.

後処理

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. concentrationThe reaction solution was concentrated to dryness 3 hours later
  3. customthe main product was purified by preparative TLC (CH2Cl2:MeOH=10:1)

出典と根拠

ORDレコード
ord-889ecb9d882f4de29e5b93f890a21948
出典データセット
uspto-grants-2009_09
特許番号
US07592005B2

反応ノート

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