AV-100-药物合成数据库

【药物名称】AV-100

化学结构式(Chemical Structure):

参考文献No.	26794
标题:	Bis(hydroxymethyl)cyclopropylmethyl pyrimidine derivs.,their preparation and their use as anti-viral agents
作者:	Onishi, T.; Mukai, C.; Sekiyama, T.; Tsuji, T.; Iwayama, S.; Okunishi, M. (Ajinomoto Co., Inc.)
来源:	EP 0649840; JP 1995165731; US 5496824

合成路线图解说明: The reaction of diethyl malonate (I) with (R)-(-)-epichlorohydrin (II) by means of sodium ethoxide in refluxing ethanol gives the 3-oxa-2-oxobicyclic compound (III), which by reduction with NaBH4 in ethanol yields (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (IV). The reaction of (IV) with diphenyldiazomethane by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloroethane affords (1R,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylic acid ethyl ester (V), which is reduced with LiBH4 in THF giving the carbinol (VI). The reaction of (VI) with CBr4 and triphenylphosphine in dichloromethane yields the bromomethyl derivative (VII), which is condensed with 5-(2-(E)-bromovinyluracil (VIII) by means of K2CO3 and 18-crown-6 in hot DMF affording the expected addition compound (IX). Finally, this compound is deprotected with HCl in methanol.

参考文献No.	563826
标题:	Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety
作者:	Onishi, T.; Mukai, C.; Nakagawa, R.; Sekiyama, T.; Aoki, M.; Suzuki, K.; Nakazawa, H.; Ono, N.; Ohmura, Y.; Iwayama, S.; Okunishi, M.; Tsuji, T.
来源:	J Med Chem 2000,43(2),278

合成路线图解说明: The reaction of diethyl malonate (I) with (R)-(-)-epichlorohydrin (II) by means of sodium ethoxide in refluxing ethanol gives the 3-oxa-2-oxobicyclic compound (III), which by reduction with NaBH4 in ethanol yields (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (IV). The reaction of (IV) with diphenyldiazomethane by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloroethane affords (1R,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylic acid ethyl ester (V), which is reduced with LiBH4 in THF giving the carbinol (VI). The reaction of (VI) with CBr4 and triphenylphosphine in dichloromethane yields the bromomethyl derivative (VII), which is condensed with 5-(2-(E)-bromovinyluracil (VIII) by means of K2CO3 and 18-crown-6 in hot DMF affording the expected addition compound (IX). Finally, this compound is deprotected with HCl in methanol.