Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP

Masayuki Kurokawa, Takeyuki Shindo, Masumi Suzuki, Nobuyoshi Nakajima, Kohji Ishihara, Takeshi Sugai

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

For the preparation of both enantiomers of N-carbamoyl-2-methoxymethylpyrrolidine, the precursors of Enders' chiral auxiliaries, SAMP and RAMP, enzyme-catalyzed kinetic resolution of racemic N-carbamoyl, N-Boc, N-Cbz proline esters and prolinols were examined. B. licheniformis protease (subtilisin) preferentially hydrolyzed the (R)-carbamoylproline ester with an enantiomeric ratio (E) of 10. To a hydrophobic N-Cbz proline ester, subtilisin showed lower selectivity (E=2.8), and in contrast, a purified protease (isozyme A) from the earthworm showed the preference of (S)-enantiomer (E=13.6). In a practical sense, C. antarctica lipase B (Chirazyme L-2) was effective for the hydrolysis of both N-Boc and N-Cbz derivatives with E >100. The e.e. of (R)-N-carbamoyl-2-methoxymethylpyrrolidine was raised to be >99.9% by recrystallization at the N-Boc-prolinol stage, which was derived from the (R)-N-Boc-proline methyl ester (98.7% e.e.) through a preparative-scale enzyme-catalyzed resolution (49% yield) of the racemic substrate.

Original languageEnglish
Pages (from-to)1323-1333
Number of pages11
JournalTetrahedron Asymmetry
Volume14
Issue number10
DOIs
Publication statusPublished - 2003 May 16

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Proline
enzymes
esters
Esters
Enzymes
routes
Subtilisin
protease
Enantiomers
enantiomers
Peptide Hydrolases
Enzyme kinetics
Oligochaeta
Lipases
Antarctic regions
Lipase
Isoenzymes
hydrolysis
Hydrolysis
selectivity

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Organic Chemistry
  • Materials Chemistry
  • Drug Discovery

Cite this

Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP. / Kurokawa, Masayuki; Shindo, Takeyuki; Suzuki, Masumi; Nakajima, Nobuyoshi; Ishihara, Kohji; Sugai, Takeshi.

In: Tetrahedron Asymmetry, Vol. 14, No. 10, 16.05.2003, p. 1323-1333.

Research output: Contribution to journalArticle

Kurokawa, Masayuki ; Shindo, Takeyuki ; Suzuki, Masumi ; Nakajima, Nobuyoshi ; Ishihara, Kohji ; Sugai, Takeshi. / Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP. In: Tetrahedron Asymmetry. 2003 ; Vol. 14, No. 10. pp. 1323-1333.
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