Ilomastat, CS-610, GM-6001, Galardin MPI, Galardin-药物合成数据库

【药物名称】Ilomastat, CS-610, GM-6001, Galardin MPI, Galardin

化学结构式(Chemical Structure):

参考文献No.	230415
标题:	Galardin (TM)
作者:	Galardy, R.E.
来源:	Drugs Fut 1993,18(12),1109

合成路线图解说明: Scheme shows the synthesis of Galardin(TM) from the two starting materials, 4-methyl-2-oxopentanoic acid sodium salt (I) and tert-butyloxycarbonyl-L-tryptophan (V). The pentanoic acid is protected as a benzyl ester and then condensed with the ylide methyl (triphenylphosphoranylidene)acetate to give methyl 3-benzyloxycarbonyl-5-methyl-2-hexenoate (III). Deprotection and reduction of (III) gives the key intermediate 2(R,S)-2-methoxycarbonylmethyl-4-methylpentanoic acid (IV) in high overall yield. The protected L-tryptophan starting material (V) is coupled with methylamine to give (VI), which is deprotected to give the second key intermediate, L-tryptophan methylamide hydrochloride (VII). Coupling of (IV) and (VII) gives the mixture of diastereomers 2(R,S)-2-methoxycarbonylmethyl-4-methylpentanoyl-L-tryptophan methylamide. Low-pressure column chromatography on silica gel gives 2(R)-2-methoxycarbonylmethyl-4-methylpentanoyl-L-tryptophan methylamide (VIII) in high yield. Direct hydroxaminolysis of the methyl ester (VIII) in methanol in the presence of potassium hydroxide gives crude Galardin(TM). Recrystallization gives the drug substance.

参考文献No.	801853
标题:	Matrix metalloproteinases: A review
作者:	Bodden, M.K.; Engler, J.A.; Moore, W.G.I.; Windsor, L.J.; Birkedal-Hansen, H.; Birkedal-Hansen, B.; DeCarlo, A.
来源:	Crit Rev Oral Biol Med 1993,4(2),197-250

合成路线图解说明: Scheme shows the synthesis of Galardin(TM) from the two starting materials, 4-methyl-2-oxopentanoic acid sodium salt (I) and tert-butyloxycarbonyl-L-tryptophan (V). The pentanoic acid is protected as a benzyl ester and then condensed with the ylide methyl (triphenylphosphoranylidene)acetate to give methyl 3-benzyloxycarbonyl-5-methyl-2-hexenoate (III). Deprotection and reduction of (III) gives the key intermediate 2(R,S)-2-methoxycarbonylmethyl-4-methylpentanoic acid (IV) in high overall yield. The protected L-tryptophan starting material (V) is coupled with methylamine to give (VI), which is deprotected to give the second key intermediate, L-tryptophan methylamide hydrochloride (VII). Coupling of (IV) and (VII) gives the mixture of diastereomers 2(R,S)-2-methoxycarbonylmethyl-4-methylpentanoyl-L-tryptophan methylamide. Low-pressure column chromatography on silica gel gives 2(R)-2-methoxycarbonylmethyl-4-methylpentanoyl-L-tryptophan methylamide (VIII) in high yield. Direct hydroxaminolysis of the methyl ester (VIII) in methanol in the presence of potassium hydroxide gives crude Galardin(TM). Recrystallization gives the drug substance.