Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety

Alberto Vega-Peñaloza, Omar Sánchez-Antonio, Margarita Escudero-Casao, Gábor Tasnádi, F. Fülöp, Eusebio Juaristi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We report the synthesis of several enantiopure pyrrolidine derivatives containing a β-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-α-pinene. Coupling of N-Boc-protected β-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in α-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz- and N-Boc-monoprotected (S)-prolinamine is reported.

Original languageEnglish
Article numberSS-2013-M0321-OP
Pages (from-to)2458-2468
Number of pages11
JournalSynthesis
Volume45
Issue number17
DOIs
Publication statusPublished - 2013

Fingerprint

Amino acids
Derivatives
Amides
Amino Acids
Terpenes
Anhydrides
Proline
Amines
Chlorides
Esters
Chemical activation
pyrrolidine
chlorosulfonyl isocyanate

Keywords

  • chiral pool
  • coupling reactions
  • enantiopure β-amino acids
  • peptides
  • stereoselective synthesis

ASJC Scopus subject areas

  • Organic Chemistry
  • Catalysis

Cite this

Vega-Peñaloza, A., Sánchez-Antonio, O., Escudero-Casao, M., Tasnádi, G., Fülöp, F., & Juaristi, E. (2013). Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety. Synthesis, 45(17), 2458-2468. [SS-2013-M0321-OP]. https://doi.org/10.1055/s-0033-1339291

Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety. / Vega-Peñaloza, Alberto; Sánchez-Antonio, Omar; Escudero-Casao, Margarita; Tasnádi, Gábor; Fülöp, F.; Juaristi, Eusebio.

In: Synthesis, Vol. 45, No. 17, SS-2013-M0321-OP, 2013, p. 2458-2468.

Research output: Contribution to journalArticle

Vega-Peñaloza, A, Sánchez-Antonio, O, Escudero-Casao, M, Tasnádi, G, Fülöp, F & Juaristi, E 2013, 'Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety', Synthesis, vol. 45, no. 17, SS-2013-M0321-OP, pp. 2458-2468. https://doi.org/10.1055/s-0033-1339291
Vega-Peñaloza A, Sánchez-Antonio O, Escudero-Casao M, Tasnádi G, Fülöp F, Juaristi E. Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety. Synthesis. 2013;45(17):2458-2468. SS-2013-M0321-OP. https://doi.org/10.1055/s-0033-1339291
Vega-Peñaloza, Alberto ; Sánchez-Antonio, Omar ; Escudero-Casao, Margarita ; Tasnádi, Gábor ; Fülöp, F. ; Juaristi, Eusebio. / Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety. In: Synthesis. 2013 ; Vol. 45, No. 17. pp. 2458-2468.
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AB - We report the synthesis of several enantiopure pyrrolidine derivatives containing a β-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-α-pinene. Coupling of N-Boc-protected β-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in α-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz- and N-Boc-monoprotected (S)-prolinamine is reported.

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