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

ABSTRACT: 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%.

SUBMITTER: Ma C

PROVIDER: S-EPMC6600510 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Ma Chunying C Chen Miao M Chu Weiming W Tao Jiayi J Kong Delong D Zhang Mengmeng M Feng Wenhua W

Molecules (Basel, Switzerland) 20190611 11

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 couplin ...[more]

PMID: 31212595

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