新产品编号:881683
Chemical Name: N-[2(R)-[1(R)-indanyl]-3-sulfanylpropionyl]-L-tryptophan
CAS No. 355016-72-7 (diastereomeric mixture)
项目整合开发状态: Biological Testing
项目研究机构: INSERM (Originator), Servier (Originator)
合成路线:The reduction of 1-indanone (I) with NaBH4 in methanol gives 1-indanol (II),which is brominated with Tms-Br in chloroform to yield 1-bromoindane (III) (1).The condensation of (III) with triethyl phosphonoacetate (IV) and NaH in DMF affords 2-(diethoxyphosphoryl)-2-(1-indanyl)acetic acid ethyl ester (V),which is treated with paraformaldehyde and K2CO3 in refluxing THF to provide 2-(1-indanyl)acrylic acid ethyl ester (VI).The hydrolysis of (VI) with NaOH in acetone/water gives the corresponding acrylic acid (VII),which is condensed with thioacetic acid (VIII) in refluxing chloroform to yield 3-(acetylsulfanyl)-2-(1-indanyl)propionic acid ethyl ester (IX) as a mixture of the two (R,R)+(S,S) and (R,S)+(S,R) racemates.These two racemates are easily separated by HPLC affording the desired (R,R)+(S,S)-(X) racemate.The condensation of (X) with L-tryptophan methyl ester (XI) by means of EDC and HOBT in THF/chloroform to provide a diastereomeric mixture (R,R,S)+(S,S,S) of compounds that is separated by HPLC to provide the desired (R,R,S) diastereomer (XII).Finally,this compound is hydrolyzed with NaOH in methanol/water to furnish the target tryptophan derivative.
📌 参考资料/链接：
参考文献标题:Amino acid derivs.and use thereof as NEP,ACE and ECE inhibitors
文献作者:Roques,B.P.; Renard,P.; Scalbert,E.; Bennejean,C.; Fournie-Lazuski,M.-C.; Inguimbert,N.; Poras,H.(ADIR et Cie.; INSERM (Institut National de la Sante et de la Recherche Medicale))
参考来源:FR 2805259; WO 0160822
📄 详细内容
合成路线:The reduction of 1-indanone (I) with NaBH4 in methanol gives 1-indanol (II),which is brominated with Tms-Br in chloroform to yield 1-bromoindane (III) (1).The condensation of (III) with triethyl phosphonoacetate (IV) and NaH in DMF affords 2-(diethoxyphosphoryl)-2-(1-indanyl)acetic acid ethyl ester (V),which is treated with paraformaldehyde and K2CO3 in refluxing THF to provide 2-(1-indanyl)acrylic acid ethyl ester (VI).The hydrolysis of (VI) with NaOH in acetone/water gives the corresponding acrylic acid (VII),which is condensed with thioacetic acid (VIII) in refluxing chloroform to yield 3-(acetylsulfanyl)-2-(1-indanyl)propionic acid ethyl ester (IX) as a mixture of the two (R,R)+(S,S) and (R,S)+(S,R) racemates.These two racemates are easily separated by HPLC affording the desired (R,R)+(S,S)-(X) racemate.The condensation of (X) with L-tryptophan methyl ester (XI) by means of EDC and HOBT in THF/chloroform to provide a diastereomeric mixture (R,R,S)+(S,S,S) of compounds that is separated by HPLC to provide the desired (R,R,S) diastereomer (XII).Finally,this compound is hydrolyzed with NaOH in methanol/water to furnish the target tryptophan derivative.
参考文献标题:Toward an optimal joint recognition of the S1' subsites of endothelin converting enzyme-1 (ECE-1),angiotensin converting enzyme (ACE),and neutral endopeptidase (NEP)
文献作者:Inguimbert,N.; Coric,P.; Poras,H.; Meudal,H.; Teffot,F.; Fourni?Zaluski,M.-C.; Roques,B.P.
参考来源:J Med Chem 2002,45(7),1477