Reference

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

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 (Department of Chemistry, Keio University, Yokohama 223-8522, Japan). Tetrahedron: Asymmetry, 14(10), 1323-1333 (English) 2003 Elsevier Science B.V. CODEN: TASYE3. ISSN: 0957-4166. DOCUMENT TYPE: Journal CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 7 For the prepn. of both enantiomers of N-carbamoyl-2-methoxymethylpyrrolidine, the precursors of Enders' chiral auxiliaries, SAMP [(2S)-1-Pyrrolidinamine, 2-(methoxymethyl)] and RAMP [(2R)-1-Pyrrolidinamine, 2-(methoxymethyl)], enzyme-catalyzed kinetic resoln. of racemic N-carbamoyl, N-Boc, N-Cbz proline esters (Boc = tert-butoxycarbonyl, Cbz = benzyloxycarbonyl) and prolinols were examd. 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 (isoenzyme 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 derivs. with E >100. The e.e. of (R)-N-carbamoyl-2-methoxymethylpyrrolidine was raised to be >99.9% by recrystn. at the N-Boc-prolinol stage, which was derived from the (R)-N-Boc-proline Me ester (98.7% e.e.) through a preparative-scale enzyme-catalyzed resoln. (49% yield) of the racemic substrate.