Formyl-leurosine → methyl (13S,15R,16R,18S)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-10-methoxycarbonyl-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-18-ethyl-17-oxa-1,11-diazapentacyclo[13.4.1.04,12.05,10.016,18]icosa-4(12),5,7,9-tetraene-13-carboxylate

HRID 354526Notes

Reaction equation

HRID 354526 reaction equation
[CH3:1][CH2:2][C@@:3]12[O:15][C@@H:14]1[C@H:12]1[CH2:13][N:5]([CH2:6][CH2:7][C:8]3[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[NH:54][C:9]=3[C@@:10]([C:50]([O:52][CH3:53])=[O:51])([C:16]3[CH:21]=[C:20]4[C@@:22]56[C@@H:33]([N:34]([CH:35]=O)[C:19]4=[CH:18][C:17]=3[O:48][CH3:49])[C@@:32]([OH:41])([C:37]([O:39][CH3:40])=[O:38])[C@H:31]([O:42][C:43]([CH3:45])=[O:44])[C@:27]3([CH2:46][CH3:47])[CH:28]=[CH:29][CH2:30][N:25]([C@H:26]53)[CH2:24][CH2:23]6)[CH2:11]1)[CH2:4]2.N1C2C(=CC=CC=2)C=C1.N1C2C(=CC=CC=2)CC1>O1CCCC1>[CH3:1][CH2:2][C@@:3]12[O:15][C@@H:14]1[C@H:12]1[CH2:13][N:5]([CH2:6][CH2:7][C:8]3[C:60]4[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=4[NH:54][C:9]=3[C@@:10]([C:50]([O:52][CH3:53])=[O:51])([C:16]3[CH:21]=[C:20]4[C@:22]56[C@@H:26]7[C@:27]([CH2:46][CH3:47])([C@@H:31]([O:42][C:43]([CH3:45])=[O:44])[C@:32]([OH:41])([C:37]([O:39][CH3:40])=[O:38])[C@@H:33]5[N:34]([CH3:35])[C:19]4=[CH:18][C:17]=3[O:48][CH3:49])[CH:28]=[CH:29][CH2:30][N:25]7[CH2:24][CH2:23]6)[CH2:11]1)[CH2:4]2

Participants

4

Reactant 2

HCID 320745Formyl-leurosineHCID 19849603Indole dihydroindole

Product 1

HCID 442111methyl (13S,15R,16R,18S)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-10-methoxycarbonyl-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-18-ethyl-17-oxa-1,11-diazapentacyclo[13.4.1.04,12.05,10.016,18]icosa-4(12),5,7,9-tetraene-13-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A process for preparing VCR and formylleurosine which comprises oxidizing a tetrahydrofuran solution of the crude dimeric indole-dihydroindole alkaloids obtainable by extraction from the leaves of Vinca rosea in which VLB and leurosine are the predominant alkaloids with an aqueous chromate-sulfuric acid oxidizing solution at a temperature in the range about -80° C. to about -50° C. until substantially all the VLB and leurosine initially present are converted to vincristine and formylleurosine respectively, optionally reformylating any 1-desformyl congeners present, and then separating vincristine and formylleurosine therefrom by chromatography.

Workup

  1. extractionobtainable by extraction from the

Sources & evidence

ORD record
ord-549df686987c4063b856617137edcaec
Source dataset
uspto-grants-1983_03
Patent number
US04375432

Reaction notes

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