TY - JOUR
T1 - Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP
AU - Kurokawa, Masayuki
AU - Shindo, Takeyuki
AU - Suzuki, Masumi
AU - Nakajima, Nobuyoshi
AU - Ishihara, Kohji
AU - Sugai, Takeshi
N1 - Funding Information:
The authors thank Meito Co. for the generous gift of C. rugosa lipase OF. We express our deep thanks to Professors Romas Kazlauskas of McGill University and Tadashi Ema of Okayama University for their discussion on enantiomeric recognition of protease-catalyzed hydrolysis, on the occasion of the 5th Japanese Symposium on the Chemistry of Biocatalysis. The authors also thank Dr. Shuji Akai of Osaka University for information on lipase-catalyzed hydrolysis of benzoates. This work was also supported by a Grant-in-Aid for Scientific Research (No.14560084) and the 21st Century COE program (KEIO LCC) from the Ministry of Education, Sports, Culture, Science, and Technology, Japan, the Monbu-Kagakusho, and is acknowledged with thanks.
PY - 2003/5/16
Y1 - 2003/5/16
N2 - 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.
AB - 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.
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U2 - 10.1016/S0957-4166(03)00210-6
DO - 10.1016/S0957-4166(03)00210-6
M3 - Article
AN - SCOPUS:0038108990
VL - 14
SP - 1323
EP - 1333
JO - Tetrahedron Asymmetry
JF - Tetrahedron Asymmetry
SN - 0957-4166
IS - 10
ER -