A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation

Molecules

Jiayi Tao¹  Mengmeng Zhang¹  Miao Chen¹  Wenhua Feng²  Chunying Ma²  Weiming Chu²  Delong Kong² 

[1] Peking Union Medical College, Beijing 100050, China;;Department of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences &

关键词: pasireotide;    liquid-phase;    synthesis;    BSA/NHS;    cyclic hexapeptide;   

DOI  :  10.3390/molecules24112185

来源: DOAJ

【 摘 要 】

Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro¹-Phe⁶ peptide bond was selected as the final cyclization position. Two key fragments were simply synthesized using N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents, and processes of the two key fragments were simple without any chromatographic purification. The current synthesis method is easily scalable and produces the target peptide with an overall yield of 15%.

【 授权许可】

Unknown