Advertisement

Archives of Pharmacal Research

, Volume 41, Issue 3, pp 259–264 | Cite as

An efficient synthetic protocol for amide derivatives of Boc-2-aminoisobutyrate

  • Minmi Jo
  • Sun-Woo Won
  • Dong Guk Lee
  • Jae-Kyung JungEmail author
  • Sunhong Kim
  • Young-Shin KwakEmail author
Research Article

Abstract

Aminoisobutyric acid (AIB) is an important building block widely incorporated by medicinal chemists in molecular design. Owing to the steric challenge, elaborating AIB’s carboxylic acid using conventional amidation protocols is often problematic. We discovered that an amidation protocol utilizing methyl Boc-aminoisobutyrate and magnesium amidates of various reactivities produces the corresponding amide derivatives in good to excellent yields.

Graphical abstract

Keywords

Methyl Boc-aminoisobutyrate Transmidation t-butylmagnesiumchloride Steric challenge 

Notes

Acknowledgement

This research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015R1A2A2A04003471).

Compliance with ethical standards

Conflict of Interest

The authors declare no conflict of interest

References

  1. Brown ZZ, Schafmeister CE (2008) Exploiting an inherent neighboring group effect of α-amino acids to synthesize extremely hindered dipeptides. J Am Chem Soc 130:14382–14383CrossRefPubMedGoogle Scholar
  2. Choi M, Won SW, Jo H, Viji M, Seo SY, Lee YJ, Lee HS, Lee H, Hong JT, Kwak YS, Jung JK (2014) A novel and efficient amidation of 2-aminothiazole. Tet Lett 55:6582–6584CrossRefGoogle Scholar
  3. Deacon CF, Knudsen LB, Madsen K, Wiberg FC, Jacobsen O, Holst JJ (1998) Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia 41:271–278CrossRefPubMedGoogle Scholar
  4. Due-Hansen M, Pandey SK, Christiansen E, Andersen R, Hansen SVF, Ulven T (2016) A protocol for amide bond formation with electron deficient amines and sterically hindered substrates. Org Biomol Chem 14:430–433CrossRefPubMedGoogle Scholar
  5. Hroch L, Hrušková M, Schmitz J, Schnakenburg G, Gütschow M (2014) 3,5,5-Trisubstituted hydantoins from activated (benzyloxycarbonylamino)malonic acids. Synthesis 44:1907–1914Google Scholar
  6. Pfau R, Priepke H, Gerlach K, Wienen W, Schuler-Metz A, Nar H, Handschuh S (2005) Substituted thiophene carboxamides. US 20050277628 A1Google Scholar
  7. Yamaguchi H, Kodama H, Osada S, Kato F, Jelokhani-Niaraki M, Kondo M (2003) Effect of α, α-dialkyl amino acids on the protease resistance of peptides. Biosci Biotechnol Biochem 67(10):2269–2272CrossRefPubMedGoogle Scholar
  8. Yang L, Marquis RW, Olson JT, Patchett AA (1997) 3-spirolactam, 3-spiroamino, 3-spirolactone and 3-spirobenzopyran piperidines and pyrrolidines promote release of growth hormone. WO 1997011697 A1Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2018

Authors and Affiliations

  1. 1.College of PharmacyKorea UniversitySejongKorea
  2. 2.College of PharmacyChungbuk National UniversityChungjuKorea
  3. 3.Korea Research Institute of Bioscience and BiotechnologyDaejeonKorea

Personalised recommendations