SB-T-1213

Chemical Name: Benzoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-[3(S)-(tert-butoxycarbonylamino)-2(R)-hydroxy-5-methyl-4-hexenoyloxy]-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-6-(propionyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methano
项目整合开发状态: Biological Testing
项目研究机构: State University of New York,Stony Brook (Originator)
合成路线:Lithium enolate (II),generated from chiral ester (I) and LDA at -84 C,was cyclocondensed with imine (III) to furnish azetidinone (IV).The N-p-methoxyphenyl group of (IV) was then removed by oxidative treatment with ceric ammonium nitrate at -10 C,and the resulting azetidinone (V) was protected with Boc2O to afford tert-butyl carbamate (VI).

合成路线:The C-7 hydroxyl group of 10-deacetyl baccatin III (VII) was selectively protected with triethylsilyl chloride and imidazole to yield silyl ether (VIII).Subsequent selective acylation of (VIII) at C-10 hydroxyl group with propionyl chloride in the presence of LiN(SiMe3)2 afforded ester (IX).The title taxoid was then obtained by further coupling with b-lactam (VI) using LiN(SiMe3)2 in THF at low temperature,followed by desilylation with HF in pyridine.

合成路线:Lithium enolate (II),generated from chiral ester (I) and LDA at -84 C,was cyclocondensed with imine (III) to furnish azetidinone (IV).After removal of the triisopropylsilyl group of (IV) using HF in pyridine,the resulting lactam was treated with CH2I2 and Et2Zn in 1,2-dichloroethane to give the dimethylcyclopropyl azetidinone (V).The C-3 hydroxyl group was reprotected as the triisopropylsilyl ether (VI).Then,the N-p-methoxyphenyl group of (VI) was removed by oxidative treatment with ceric ammonium nitrate at -10 C,and the resulting azetidinone was N-protected with Boc2O to afford tert-butyl carbamate (VII).

合成路线:The C-7 hydroxyl group of 10-deacetyl baccatin III (VIII) was selectively protected with triethylsilyl chloride and imidazole to yield silyl ether (IX).Subsequent selective acetylation of (IX) at C-10 hydroxyl group with acetyl chloride in the presence of LiN(SiMe3)2 afforded ester (X).The title taxoid was then obtained by further coupling of (X) with b-lactam (VII) using LiN(SiMe3)2 in THF at low temperature,followed by desilylation with HF in pyridine.

合成路线:Lithium enolate (II),generated from chiral ester (I) and LDA at -84 C,was cyclocondensed with imine (III) to furnish azetidinone (IV).After removal of the triisopropylsilyl group of (IV) using HF in pyridine,the resulting lactam was treated with CH2I2 and Et2Zn in 1,2-dichloroethane to give the dimethylcyclopropyl azetidinone (V).The C-3 hydroxyl group was reprotected as the triisopropylsilyl ether (VI).Then,the N-p-methoxyphenyl group of (VI) was removed by oxidative treatment with ceric ammonium nitrate at -10 C,and the resulting azetidinone was N-protected with Boc2O to afford tert-butyl carbamate (VII).

合成路线:The C-7 hydroxyl group of 10-deacetyl baccatin III (VIII) was selectively protected with triethylsilyl chloride and imidazole to yield silyl ether (IX).Subsequent selective acylation of (IX) at C-10 hydroxyl group with cyclopropanecarbonyl chloride (X) in the presence of LiN(SiMe3)2 afforded ester (XI).The title taxoid was then obtained by further coupling of (XI) with b-lactam (VII) using LiN(SiMe3)2 in THF at low temperature,followed by desilylation with HF in pyridine.