CI-1029, PD-178390-药物合成数据库

【药物名称】CI-1029, PD-178390

化学结构式(Chemical Structure):

参考文献No.	562947
标题:	Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: A lead HIV protease inhibitor
作者:	Vara Prasad, J.V.N.; Boyer, F.E.; Domagala, J.M.; Ellsworth, E.L.; Gajda, C.; Hamilton, H.W.; Hagen, S.E.; Markoski, L.J.; Steinbaugh, B.A.; Tait, B.D.; Humblet, C.; Lunney, E.A.; Pavlovsky, A.; Rubin, J.R.; Ferguson, D.; Graham, N.; Holler, T.; et al.
来源:	Bioorg Med Chem 1999,7(12),2775

合成路线图解说明: The condensation of 5-[4-(tert-butoxycarbonylamino)phenyl]-2-methyl-3-pentanone (I) with tert-butylacetate (II) by means of LDA in THF, followed by hydrolysis of the ether with LiOH gives the racemic 3-hydroxypentanoic acid (III), which is submitted to optical resolution with (S)-alpha-methylbenzylamine affording the (S)-enantiomer (IV). The condensation of (IV) with the magnesium salt of monoethyl malonate (V) affords the beta-keto ester (VI), which is cyclized by means of NaOH to provide the dihydropyrone (VII). The condensation of (VII) with thiosulfonate (VIII) by means of K2CO3 in DMF yields the expected thioether (IX), which is finally treated with NaOH in DMSO/water to eliminate the tert-butoxycarbonyl protecting group.

参考文献No.	603214
标题:	Application of the Sch鰌f method to optimization of the synthesis of 3-[2-(p-N-acetylaminophenyl)ethyl]-3-hydroxy-4-methylpentanoic acid: Simultaneous reduction of three functional groups to maximine yield and throughput
作者:	Deering, C.F.; et al.
来源:	Org Process Res Dev 2000,4(6),596

合成路线图解说明: The hydrolysis of the ketoester (I) with NaOH gives the corresponding ketoacid (II), which is condensed with 4-nitrobenzaldehyde (III) by means of pyridine to yield the hydroxyketone (IV). The reaction of (IV) with acetic anhydride and pyridine affords the acetoxy compound (V), which is dehydrated by means of hot pyridine to provide the enone (VI). The condensation of (VI) with benzyl acetate (VII) by means of LDA gives 3-hydroxy-3-isopropyl-5-(4-nitrophenyl)-4-pentenoic acid benzyl ester (VIII), which is fully hydrogenated with H2 over Pd(OH)2 to yield the amino acid (IX). Finally, (IX) is treated with acetic anhydride to afford the target 5-(4-acetamidophenyl)-3-hydroxy-3-isopropylpentanoic acid intermediate (X).