Naxifylline, BG-9719, CVT-124, Adentri
1H-嘌呤-2,6-二酮,3,9-二氢-8-(1S,2R,4S,5S,6S)-3-奥沙三环[3.2.1.02,4]辛-6-基-1,3-二丙基- 1H-Purine-2,6-二酮,3,9-二氢-8-(1S,2R,4S,5S,6R)-3-氧三环[3.2.1.02,4]辛-6-基-1,3-二丙基- Chemical Name: (1S,2R,3S,4S,6S)-8-[3-Oxatricyclo[3.2.1.0(2,4)]oct-6-yl]-1,3-dipropylxanthine
CAS No. 166374-49-8, 166374-48-7 ((6R)-isomer), 166181-76-6 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: University of Florida (Originator), Biogen Idec (Licensee), CV Therapeutics (Licensee)
合成路线:The asymmetric Diels-Alder cycloaddition of cyclopentadiene (II) with the acrylic ester (I) of the chiral auxiliary D-pantolactone catalyzed by TiCl4 gives the chiral norbornene (III),which is treated with LiOH or NaOH to eliminate the auxiliary to yield the carboxylic acid (IV).The reaction of (IV) with oxalyl chloride affords the acyl chloride (V),which is condensed with 5,6-diamino-1,3-dipropyluracil (VI) by means of DMAP in pyridine to provide the amide (VII).The cyclization of (VII) by means of NaOH in dioxane gives the 1,3-dipropylxanthine derivative (VIII),which is finally epoxidated by means of magnesium monoperphthalate (MMPP) in aq.isopropanol to furnish the target xanthine derivative.
📌 参考资料/链接：
参考文献标题:Novel A1 adenosine receptor agonists and antagonists
文献作者:Belardinelli,L.; Olsson,R.; Baker,S.; Scammells,P.J.; Milner,P.G.; Pfister,J.R.; Schreiner,G.F.(University of Florida)
参考来源:EP 0725782; JP 1997507052; US 5446046; WO 9511904
📄 详细内容
合成路线:The asymmetric Diels-Alder cycloaddition of cyclopentadiene (II) with the acrylic ester (I) of the chiral auxiliary D-pantolactone catalyzed by TiCl4 gives the chiral norbornene (III),which is treated with LiOH or NaOH to eliminate the auxiliary to yield the carboxylic acid (IV).The reaction of (IV) with oxalyl chloride affords the acyl chloride (V),which is condensed with 5,6-diamino-1,3-dipropyluracil (VI) by means of DMAP in pyridine to provide the amide (VII).The cyclization of (VII) by means of NaOH in dioxane gives the 1,3-dipropylxanthine derivative (VIII),which is finally epoxidated by means of magnesium monoperphthalate (MMPP) in aq.isopropanol to furnish the target xanthine derivative.
参考文献标题:Synthesis and biological evaluation of the enantiomers of the potent and selective A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbonyl)]xanthine
文献作者:Pfister,J.R.; Belardinelli,L.; Lee,G.; Lum,R.T.; Milner,P.; Stanley,W.C.; Linden,J.; Baker,S.P.; Schreiner,G.
参考来源:J Med Chem 1997,40(12),1773