Epoxyquinomicin B
2-羟基-N-[(1R,6S)-1-(羟基甲基)-2,5-二氧代-7-氧杂双环[4.1.0]庚-3-烯-4-基]苯甲酰胺Chemical Name: N-[4(R),5(S)-Epoxy-4-(hydroxymethyl)-3,6-dioxo-1-cyclohexenyl]-2-hydroxybenzamide
CAS No. 175448-32-5
项目整合开发状态: Preclinical
项目研究机构: Mercian (Originator), Microbial Chemistry Research Foundation (Originator)
合成路线:A synthesis of the racemic compound was later reported:3-Hydroxy-4-nitrobenzaldehyde (I) was reduced to the benzyl alcohol (II) with NaBH4 and then converted to diacetate (III) with Ac2O in pyridine.Selective deacetylation of the aryl ester of (III) with KHCO3 in MeOH produced phenol (IV),which was then acylated with acetylsalicyloyl chloride (V) to yield (VI).The catalytic hydrogenation of the nitro group of (VI) in the presence of Raney-Ni was accompanied by migration of the salicyloyl unit to the amino group to yield salicylamide (VII) (accompanied by some byproduct resulting from the cleavage of the phenolic acetate).The resultant mixture of mono- and diacetate was converted to triol (VIII) by hydrolysis in aqueous NaOH.Then,the aminophenol ring of (VIII) was selectively oxidized with Fremy's salt to quinone (IX).Finally,the quinone was treated with H2O2 in the presence of NaHCO3 to furnish the racemic epoxide.
📌 参考资料/链接：
参考文献标题:Synthesis of anti-rheumatic agent epoxyquinomicin B
文献作者:Matsumoto,N.; Iinuma,H.; Sawa,T.; Takeuchi,T.
参考来源:Bioorg Med Chem Lett 1998,8(21),2945
📄 详细内容
合成路线:A synthesis of the racemic compound was later reported:3-Hydroxy-4-nitrobenzaldehyde (I) was reduced to the benzyl alcohol (II) with NaBH4 and then converted to diacetate (III) with Ac2O in pyridine.Selective deacetylation of the aryl ester of (III) with KHCO3 in MeOH produced phenol (IV),which was then acylated with acetylsalicyloyl chloride (V) to yield (VI).The catalytic hydrogenation of the nitro group of (VI) in the presence of Raney-Ni was accompanied by migration of the salicyloyl unit to the amino group to yield salicylamide (VII) (accompanied by some byproduct resulting from the cleavage of the phenolic acetate).The resultant mixture of mono- and diacetate was converted to triol (VIII) by hydrolysis in aqueous NaOH.Then,the aminophenol ring of (VIII) was selectively oxidized with Fremy's salt to quinone (IX).Finally,the quinone was treated with H2O2 in the presence of NaHCO3 to furnish the racemic epoxide.
参考文献标题:Epoxyquinomicins A,B,C and D,new antibiotics from Amycolatopsis.I.Taxonomy,fermentation,isolation and antimicrobial activities
文献作者:Matsumoto,N.; Tsuchida,T.; Umekita,M.; Kinoshita,N.; Iinuma,H.; Sawa,T.; Hamada,M.; Takeuchi,T.
参考来源:J Antibiot 1997,50(11),900
合成路线:The condensation of 4-(tert-butyldimethylsilyloxymethyl)aniline (I) with 2-(acetoxy)benzoyl chloride (II) by means of TEA in dichloromethane gives the corresponding amide (III),which is oxidized with DMP in dichloromethane to yield the benzoquinone (IV).The reaction of (IV) with H2O2 and K2CO3 affords the epoxide (V),which is finally desilylated with HF and pyridine in THF to provide the target compound.
参考文献标题:New synthetic technology for the construction of N-containing quinones and derivatives thereof: Total synthesis of epoxyquinomycin B
文献作者:Nicolaou,K.C.; et al.
参考来源:Angew Chem.Int Ed Engl 2001,40(1),207
产品链接: CAS No. 175448-32-5››