Convergent Total Synthesis of Yaku'amide A

• Published in: Angewandte Chemie International Edition Vol. 60; no. 10; pp. 5162 - 5167
• Main Authors: Cai, Yu, Ma, Zhiwei, Jiang, Jintao, Lo, Concordia C. L., Luo, Shi, Jalan, Ankur, Cardon, Joseph M., Ramos, Alexander, Moyá, Diego A., Joaquin, Daniel, Castle, Steven L.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-03-2021
• Edition: International ed. in English
• Subjects: Amino acids; aminohydroxylation; Antineoplastic Agents - chemical synthesis; Convergence; Dehydration; Hydroxylation; Isomerization; Natural products; Oligopeptides - chemical synthesis; O→N acyl transfer; peptides; Reagents; Stereoisomerism; Synthesis; total synthesis; natural products; peptides; total synthesis; aminohydroxylation; O→N acyl transfer
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202014238

Total synthesis of the anticancer peptide natural product yaku'amide A is reported. Its β‐tert‐hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E‐ and Z‐ΔIle residues was accomplished through a one‐pot reaction featuring anti dehydration, azide reduction, and O→N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product.
Yaku'amide A, an anticancer peptide, was synthesized by a route featuring a one‐pot anti dehydration–azide reduction–O→N acyl transfer process for stereospecific construction of the E‐ and Z‐ΔIle residues. The β‐hydroxy amino acids were produced by aminohydroxylation catalyzed by OsO4.