Synthesis and Evaluation of Cyclic Acetals of Serine Hydroxylamine for Amide-Forming KAHA Ligations

Simon Baldauf; Jeffrey W. Bode

doi:10.1055/s-0037-1611635

Synthesis, Table of Contents

CC BY-ND-NC 4.0 · Synthesis 2019; 51(05): 1273-1283
DOI: 10.1055/s-0037-1611635

paper

Copyright with the author

Synthesis and Evaluation of Cyclic Acetals of Serine Hydroxylamine for Amide-Forming KAHA Ligations

Simon Baldauf

^aLaboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland Email: bode@org.chem.ethz.ch

,

Jeffrey W. Bode *

^aLaboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland Email: bode@org.chem.ethz.ch

^bInstitute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan

› Author Affiliations

Abstract

All articles of this category

Abstract

The α-ketoacid–hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments. The most widely used variant employs a 5-membered cyclic hydroxylamine that forms a homoserine ester as the primary ligation product. While very effective, monomers that give canonical amino acid residues are in high demand. In order to preserve the stability and reactivity of cyclic hydroxylamines, but form a canonical amino acid residue upon ligation, we sought to prepare cyclic derivatives of serine hydroxylamine. An evaluation of several cyclization strategies led to cyclobutanone ketals as the leading structures. The preparation, stability, and amide-forming ligation of these serine-derived ketals are described.

Key words

ligation - hydroxylamines - acetals - amides - peptides

Full Text

References

References
1 Bode JW, Fox RM, Baucom KD. Angew. Chem. Int. Ed. 2006; 45: 1248
2 Dawson PE, Muir TW, Clark-Lewis I, Kent SB. Science (Washington, D. C.) 1994; 266: 776

Other amide-forming ligations include the traceless Staudinger and the serine/threonine ligation:

3a Kleineweischede R, Hackenberger CP. R. Angew. Chem. Int. Ed. 2008; 47: 5984
3b Zhang Y, Xu C, Lam HY, Lee CL, Li X. Proc. Natl. Acad. Sci. U.S.A. 2013; 110: 6657

4 Pattabiraman VR, Ogunkoya AO, Bode JW. Angew. Chem. Int. Ed. 2012; 51: 5114
5 Wucherpfennig TG, Rohrbacher F, Pattabiraman VR, Bode JW. Angew. Chem. Int. Ed. 2014; 53: 12244
6 Pusterla I, Bode JW. Nat. Chem. 2015; 7: 668

7a Tokuyama H, Kuboyama T, Amano A, Yamashita T, Fukuyama T. Synthesis 2000; 1299
7b Tokuyama H, Kuboyama T, Fukuyama T. Org. Synth. 2003; 80: 207
7c Medina SI, Wu J, Bode JW. Org. Biomol. Chem. 2010; 8: 3405

8a Knowles DA, Mathews CJ, Tomkinson NC. O. Synlett 2008; 2769
8b Knight DW, Leese MP. Tetrahedron Lett. 2001; 42: 2593
8c Jones KL, Porzelle A, Hall A, Woodrow MD, Tomkinson NC. O. Org. Lett. 2008; 10: 797
8d Blakemore PR. Science of Synthesis . Vol. 21. Georg Thieme Verlag; Stuttgart: 2005: 857

9 Rohrbacher F, Baldauf S, Wucherpfennig TG, Bode JW. Synlett 2017; 28: 1929

10a Greene TW, Wuts PG. M. Protective Groups in Organic Synthesis . John Wiley & Sons; New York: 1999. 4rd ed. 300-302
10b Rich RH, Bartlett PA. J. Org. Chem. 1996; 61: 3916

11 Rohrbacher F, Zwicky A, Bode JW. Chem. Sci. 2017; 8: 4051

Supplementary Material

Supporting Information