Pravastatin sodium, Eptastatin sodium, SQ-31000, CS-514, Pravaselect, Liplat, Pravachol, Lipostat, Vasten, Selectin, Elisor, Mevalotin

普伐他汀钠 普伐他汀 Chemical Name: [1S-[1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha]]-1,2,6,7,8,8a-Hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthaleneheptanoic acid monosodium salt; (+)-(betaR,deltaR,1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-Hexahydro-beta,delta,6,8-tetrahydroxy-2-methyl-1-naphthaleneheptanoic acid sodium salt 8-[(2S)-2-methylbutyrate]
CAS No. 81131-70-6, 81093-37-0 (free acid)
项目整合开发状态: Launched-1989
项目研究机构: Sankyo (Originator), Bristol-Myers Squibb (Licensee), Esteve (Licensee), Menarini (Licensee)
合成路线:The synthesis of [14C]-labeled pravastatin has been reported: The reaction of propylmagnesium bromide (I) with (14)CO2 gives [14C]-butyric acid sodium salt (II),which is converted to the corresponding acyl chloride (III) by reaction with oxalyl chloride.The condensation of (III) with 4(S)-benzyloxazolidin-2-one (IV) in THF yields the corresponding acylation product (V),which is methylated with sodium hexamethyldisilazide and methyliodide to afford a mixture of tautomeric N-[4(S)-benzyl-3-[2(R and S)-methylbutyryl]oxazolidin-2-ones,which are separated by preparative HPLC to obtain the optically pure diastereomer (VI).The oxidative cleavage of (VI) with H2O2 and LiOH,followed by acidification and treatment with NaOH,yields sodium 2(S)-methylbutyrate (VII),which is treated with oxalyl chloride to afford the corresponding acyl chloride (VIII).The condensation of (VIII) with 4(R)-(tert-butyldimethylsilyloxy)-6(R)-[2-[8(S)-hydroxy-2(S)-methyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl]ethyl]tetrahydropyran-2-one (IX) by means of 4-(dimethylamino)pyridine in CH2Cl2 gives the esterified compound (X),which is deprotected with tetrabutylammonium fluoride and acetic acid,yielding the hydroxylated pyrone (XI).Finally,this compound is submitted to an asymmetric hydroxylation with a culture broth of Mucor hiemalis MF-5021.The final product is extracted from the culture broth and purified by preparative HPLC to give a final radiochemical purity of 95%.