【药物名称】Azalanstat dihydrochloride, Azalanstat hydrochloride, RS-21607-197
化学结构式(Chemical Structure):
参考文献No.19256
标题:1,3-Dioxolane derivs. as cholesterol lowering agents
作者:Walker, K.A.; Burton, P.M.; Swinney, D.C. (Syntex (USA), Inc.)
来源:JP 1992308588; US 5158949
合成路线图解说明:

Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献No.22979
标题:Process for preparing 1,3-dioxolane derivs
作者:Dyson, N.H.; Gardner, J.O.; Prince, A.; Kertesz, D.J. (Syntex (USA), Inc.)
来源:JP 1995508002; US 5208331
合成路线图解说明:

Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献No.238214
标题:RS-21607-197
作者:Prous, J.; Mealy, N.; Casta馿r, J.
来源:Drugs Fut 1994,19(2),125
合成路线图解说明:

Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献No.242982
标题:Selective inhibition of mammalian lanosterol 14alpha-demethylase: A possible strategy for cholesterol lowering
作者:Walker, K.A.M.; Kertesz, D.J.; Rotstein, D.M.; Swinney, D.C.; Berry, P.W.; So, O.Y.; Webb, A.S.; Watson, D.M.; Mak, A.Y.; Burton, P.M.; et al.
来源:J Med Chem 1993,36(15),2235-7
合成路线图解说明:

Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

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