Enantioselective Synthesis of Fmoc-Protected (2S,3R)-3,4-Dimethyl-2-(methylamino)pentanoic Acid

Abstract

The first enantioselective synthesis of the Fmoc-protected rare amino acid, 3,4-dimethyl-2-(methylamino)pentanoic acid, is disclosed. The synthesis utilized the chiral oxazolidinone to introduce the first chiral center (>95:5 ee), and then swapped the auxiliary to Ellman’s N-sulfinylimine for setting up the chiral α-amino group (95:5 dr). The newly formed chiral centers were confirmed by X-ray crystallography. With this unique amino acid on hand, naturally occurring macrocyclic peptides will become synthetically accessible.

Key words

enantioselective synthesis - amino acid - etamycins A - triostin C - echinomycin C

Publikationsverlauf

Eingereicht: 06. März 2025

Angenommen nach Revision: 31. März 2025

Accepted Manuscript online:
31. März 2025

Artikel online veröffentlicht:
15. Mai 2025

• References

• 1 Sheehan JC. J. Am. Chem. Soc. 1957; 80: 3349
• 2 Mukhopadhyay T, Franco CM. M, Bhat RG, Sawant SN, Ganguli BN, Rupp RH, Fehlhaber H.-W, Teetz V. Tetrahedron 1998; 54: 7625
• 3 Corbaz R, Ettlinger L, Gaumann E, Keller-Schierlein W, Kradolfer F, Neipp L, Prelog V, Reusser P, Zahner H. Helv. Chim. Acta 1957; 40: 199
• 4 Yoshida T, Katagiri K, Yokozawa SI. J. Antibiot., Ser. A 1961; 14: 330
• 5 Davis FA, Portonovo PS, Reddy RE, Chiu Y.-h. J. Org. Chem. 1996; 61: 440
• 6 Davis FA, Lee S, Zhang H, Fanelli DL. J. Org. Chem. 2000; 65: 8704
• 7 Robak MT, Herbage MA, Ellman JA. Chem. Rev. 2010; 110: 3600
• 8 Mabic S, Cordi AA. Tetrahedron 2001; 57: 8861
• 9 Tanasova M, Anyika M, Borhan B. Angew. Chem. Int. Ed. 2015; 54: 4274
• 10 Evans DA, Ennis MD, Mathre DJ. J. Am. Chem. Soc. 1982; 104: 1737
• 11 Dickson HD, Smith SC, Hinkle KW. Tetrahedron Lett. 2004; 45: 5597
• 12 Freidinger RM, Hinkle JS, Perlow DS. J. Org. Chem. 1983; 14: 77