Colchicine, N-deacetyl-10-thio- → 5,6-dihydro-6(S)-(hydroxymethyl)-1,2,3-trimethoxy-9-methylthio-8H-cyclo-hepta[a]naphthalen-8-one
Reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[CH2:9][CH2:10][C@H:11](N)[C:12]3[C:19]([C:6]2=[C:5]([O:23][CH3:24])[C:4]=1[O:25][CH3:26])=[CH:18][CH:17]=[C:16]([S:20][CH3:21])[C:14](=[O:15])[CH:13]=3.N([O-])=[O:28].[Na+]>>[OH:28][CH2:11][C@H:10]1[CH2:9][C:7]2[CH:8]=[C:3]([O:2][CH3:1])[C:4]([O:25][CH3:26])=[C:5]([O:23][CH3:24])[C:6]=2[C:19]2=[CH:18][CH:17]=[C:16]([S:20][CH3:21])[C:14](=[O:15])[CH:13]=[C:12]12Participants
3
Procedure
10 g of N-desacetylthiocolchicine are treated with sodium nitrite to give 4 g of 5,6-dihydro-6(S)-(hydroxymethyl)-1,2,3-trimethoxy-9-methylthio-8H-cyclo-hepta[a]naphthalen-8-one, according to the process described in J. Med. Chem., 36, 544, 1993. The resulting product is treated for 12 hours under reflux in acetonitrile with 26 g of α-bromotetraacetylglucose in the presence of 85 g of mercuric cyanide. Salts are filtered off and the solution is evaporated to dryness, taken up with 70% acetone and treated for two hours with 15% sodium carbonate. The mixture is neutralized, extracted with ethyl acetate and chromatographed on silica gel eluting with a methylene chloride-ethanol 9:1 mixture. 2.1 g of product are obtained, M+ a m/z 536.
Sources & evidence
- ORD record
- ord-939463a9cfcc49e3aef76727c48a14c8
- Source dataset
- uspto-grants-1998_12
- Patent number
- US05843910
Reaction notes
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