他达拉非对映异构体的合成与表征
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摘要
本文阐述了一种制备他达拉非对映异构体的方法,以L-色氨酸甲酯盐酸盐和胡椒醛为原料,经Pictet-Spengler反应、酰化、亲核取代和胺酯缩合制备了他达拉非对映异构体,并通过ESI-MS、比旋度、IR、~1HNMR和~(13)CNMR对目标化合物进行了结构确证。培养得到目标化合物的单晶,并利用X-射线单晶衍射对目标化合物的晶体的立体结构进行解析,进一步确定了目标化合物的结构和立体构型。
The enantiomer of Tadalafil was synthesized from L-tryptophan methyl ester hydrochloride and piperaldehyde by Pictet-Spengler reaction, acylation, nucleophilic substitution and Amine-ester condensation. The target compound was characterized by ESI-MS, specific rotation, IR, ~1HNMR and ~(13)CNMR. And the three-dimensional structure of the target compound was analyzed by X-ray single crystal diffraction.
The enantiomer of Tadalafil was synthesized from L-tryptophan methyl ester hydrochloride and piperaldehyde by Pictet-Spengler reaction, acylation, nucleophilic substitution and Amine-ester condensation. The target compound was characterized by ESI-MS, specific rotation, IR, ~1HNMR and ~(13)CNMR. And the three-dimensional structure of the target compound was analyzed by X-ray single crystal diffraction.
引文
[1]刘智勇,孙颖浩.他达拉非在阴茎勃起功能障碍中的疗效评价[J].中华男科学杂志,2008,14(4):377-380.
[2]张刚,梁兴忠,彭瑞,等.他达拉非对伴性功能障碍的前列腺炎患者的疗效[J].中外医疗,2018(25):96-98.
[3]徐波,宋宁,蒋国印,等.他达拉非治疗肺动脉高压研究现况[J].临床荟萃,2011,26(14):1278-1282.
[4]要少波,蔡明德,卢小逸,等.他达拉非合成研究进展[J].精细与专用化学品,2011,19(10):37-44.
[5]Jefferson D Revell,Natarajan Srinivasan,Ganesan A.Two Concise Syntheses of Cialis via the N-Acyliminium Pictet-Spengler Reaction[J].Synlett,2004(8),1428-1430.
[6]Alain Daugan,Pascal Grondin,Ce′cile Ruault,et al.The Discovery of Tadalafil:A Novel and Highly Selective PDE5 Inhibitor.2:2,3,6,7,12,12a-hexahydropyrazino[1￠,2￠:1,6]pyrido[3,4-b]indole-1,4-dione Analogues[J].Journal of Medicinal Chemistry,2003,46(21):4533-4542.
[7]伍普华,谢义鹏.他达拉非合成路线图解[J].中国药物化学杂志,2015,25(5):407-410.
1HNMR和13CNMR对目标化合物进行了结构的确证。通过培养
[2]张刚,梁兴忠,彭瑞,等.他达拉非对伴性功能障碍的前列腺炎患者的疗效[J].中外医疗,2018(25):96-98.
[3]徐波,宋宁,蒋国印,等.他达拉非治疗肺动脉高压研究现况[J].临床荟萃,2011,26(14):1278-1282.
[4]要少波,蔡明德,卢小逸,等.他达拉非合成研究进展[J].精细与专用化学品,2011,19(10):37-44.
[5]Jefferson D Revell,Natarajan Srinivasan,Ganesan A.Two Concise Syntheses of Cialis via the N-Acyliminium Pictet-Spengler Reaction[J].Synlett,2004(8),1428-1430.
[6]Alain Daugan,Pascal Grondin,Ce′cile Ruault,et al.The Discovery of Tadalafil:A Novel and Highly Selective PDE5 Inhibitor.2:2,3,6,7,12,12a-hexahydropyrazino[1￠,2￠:1,6]pyrido[3,4-b]indole-1,4-dione Analogues[J].Journal of Medicinal Chemistry,2003,46(21):4533-4542.
[7]伍普华,谢义鹏.他达拉非合成路线图解[J].中国药物化学杂志,2015,25(5):407-410.
1HNMR和13CNMR对目标化合物进行了结构的确证。通过培养