mp 104-105 °C; IR (KBr) 3370, 3309, 1661, 1654 cm-1; 1H NMR
(DMSO-d6) δ 7.40 (s, 1H, CONHH), 7.24 (d, J ) 7.9 Hz, 2H,
ArH), 7.08 (d, J ) 7.9 Hz, 2H, ArH), 6.91 (s, 1H, CONHH), 4.21
(s, 1H, CH), 2.25 (s, 3H, CH3); MS (EI) m/z 120 ([M - CONH2]+,
100%). Anal. Calcd for C9H12N2O: C, 65.83; H, 7.37; N, 17.06.
Found: C, 65.50; H, 7.67; N, 17.36.
En zym a tic Hyd r olysis of DL-Cycloh exylglycin e Nitr ile
(1i). D-(-)-Cyclohexylglycine amide 2i as a white solid: 21 h
(45%); [R]25 -20 (c 0.5, MeOH); ee 88% (HPLC analysis of the
D
corresponding N-benzoylated compound); mp 145-146 °C; IR
(KBr) 3349, 3258 (sh) 3195 cm-1; 1H NMR (DMSO-d6) δ 7.23 (s,
1H, CONHH), 6.88 (s, 1H, CONHH), 2.83 (d, J ) 5.1 Hz, 1H,
CH), 1.43-1.67 (m, 6H), 0.91-1.18 (m, 5H); 13C NMR (DMSO-
d6) δ 177.2, 59.8, 41.8, 29.8, 27.5, 26.24, 26.20, 26.0; MS (FAB)
m/z 156 (M+), 155 ([M - 1]+). Anal. Calcd for C8H16N2O: C,
61.51; H, 10.32; N, 17.93. Found: C, 61.18; H, 10.30; N, 17.74.
L-(+)-4-Methyphenylglycine (3d ) as white powder: 3 h (50%);
[R]25 +175 (c 0.9, 1 N HCl)) [lit.15 [R]23 +151 (c 1.0, 1N HCl);
D
D
ee >99% (HPLC); mp 247 °C (lit.20 mp 244 °C); H NMR (D2O)
δ 7.14 (s, 4H, ArH), 4.95 (s, 1H, CH), 2.14 (s, 3H, CH3).
En zym a tic Hyd r olysis of DL-2-Meth yp h en ylglycin e Ni-
tr ile (1e). D-(-)-2-Methyphenylglycine amide 2e as white
1
L-(+)-Cyclohexylglycine 3i as a white solid: 21 h (47%); [R]25
D
+28 (c 0.5, 1 N HCl) [lit.23 [R]25D +31.3 (c 1.0 1N HCl)]; ee >99%
(HPLC analysis of the corresponding N-benzoylated compound);
mp 255 °C dec (lit.23 mp >300 °C); IR (KBr) 2611-3020, 1595
(sh), 1584 cm-1; 1H NMR (D2O) δ 3.32 (d, J ) 5.2, 1H, CH), 0.52-
1.16 (m, 11H); MS (FAB) m/z 157 (M+), 156 ([M - 1]+). Anal.
Calcd for C8H15NO2: C, 61.12; H, 9.62; N, 8.91. Found: C, 60.90;
H, 9.71; N, 8.91.
powder: 12 h (45%); [R]25 -72 (c 1.0, MeOH); ee 80% (HPLC);
D
mp 117-118 °C; IR (KBr) 3351, 3274, 1661, 1618 cm-1; 1H NMR
(DMSO-d6) δ 7.39 (s, 1H, CONHH), 7.09-7.28 (m, 5H, ArH and
CONHH), 4.42 (s, 1H, CH), 2.34 (s, 3H, CH3); MS (EI) m/z 120
([M - CONH2]+, 100%). Anal. Calcd for C9H12N2O: C, 65.83; H,
7.37; N, 17.06. Found: C, 65.98; H, 7.78; N, 17.27.
En zym a tic Hyd r olysis of DL-P h en yla la n in e Nitr ile (1j).
L-(+)-2-Methyphenylglycine 3e as white powder: 12 h (42%);
[R]25 +172 (c 0.5, 1 N HCl); ee >99% (HPLC); mp 211 °C; IR
D-(-)-Phenylalanine amide (2j) as a white powder: 0.7 h (48%);
D
[R]25 -9 (c 1.0, MeOH); ee 77% (HPLC); mp 135-137 °C; IR
(KBr) 2620-3148, 1675, 1632, 1618 cm-1; 1H NMR (D2O) δ 7.23-
7.30 (m, 4H, ArH), 4.93 (s, 1H, CH), 2.37 (s, 3H, CH3); MS (EI)
m/z 120 ([M - CO2H]+, 100%). Anal. Calcd for C9H11NO2: C,
65.44; H, 6.71; N, 8.48. Found: C, 65.29; H, 6.67; N, 8.32.
En zym ztic Hyd r olysis of DL-4-Meth oxyp h en ylglycin e
Nitr ile (1f). D-(-)-4-Methoxyphenylglycine amide (2f) as white
powder: 1.5 (45%); [R]25D -80 (c 0.25, MeOH); ee >99% (HPLC);
mp 159 °C; IR (KBr) 3404, 3368, 3359, 3205, 1634 cm-1; 1H NMR
(DMSO-d6) δ 7.39 (s, 1H, CONHH), 7.27 (d, J ) 8.5 Hz, 2H,
ArH), 6.94 (s, 1H, CONHH), 6.84 (d, J ) 8.5 Hz, 2H, ArH), 4.19
(s, 1H, CH), 3.70 (s, 3H, CH3O); MS (EI) m/z 136 ([M - CONH2]+,
100%); MS (FAB) 166 ([M + 1]+). Anal. Calcd for C9H12N2O2:
C, 59.99; H, 6.71; N, 15.55. Found: C, 59.64; H, 6.86; N, 15.34.
L-(+)-4-Methoxyphenylglycine (3f) as white powder: 1.5 h
(51%); [R]25 +153 (c 0.9, 1 N HCl) [lit.21 [R]23 +156 (c 1.0, 3N
D
(KBr) 3338, 3182, 1667 cm-1; H NMR (DMSO-d6) δ 7.16-7.31
1
(m, 6H, ArH and CONHH), 6.96 (s, 1H, CONHH), 3.29-3.34
(m, 1H, CH), 2.90 (dd, J ) 13.3, 5.1 Hz, 1H), 2.58 (dd, J ) 13.3,
8.4 Hz, 1H); MS (FAB) m/z 164 (M+), 163 ([M - 1]+). Anal. Calcd
for C9H12N2O: C, 65.83; H, 7.37; N, 17.06. Found: C, 65.43; H,
7.53; N, 16.98.
L-Phenylalanine (3i) as a white solid: 0.7 h (42%); [R]25 -2
D
20
(c 1.0, 1 N HCl) (lit.2424 [R]D +7.07 (c 1.0, 1 N HCl), D-(+)-
phenylalanine); ee 51% (HPLC); mp 258 °C dec (lit.24 mp 271
°C dec, dL-phenylalanine); IR (KBr) 2554-3339, 1589 cm-1; 1H
NMR (D2O) δ 6.98-7.13 (m, 5H, ArH), 4.04 (dd, J ) 7.5, 5.9 Hz,
1H, CH), 3.04 (dd, J ) 14.9, 5.6 Hz, 1H), 2.90 (dd, J ) 14.9, 7.7
Hz, 1H).
En zym a tic Hyd r olysis of DL-Va lin e Nitr ile (1k ). D-Valine
amide (2k ) as a white solid: 1.2 h (48%); ee 22% (HPLC analysis
of the corresponding N-benzoylated compound); mp 80-83 °C;
IR (KBr) 3356, 1664, 1607 cm-1; 1H NMR (DMSO-d6) δ 7.22 (s,
1H, CONHH), 6.87 (s, 1H, CONHH), 2.82 (d, J ) 5.0 Hz, 1H,
CH), 1.72-1.88 (m, 1H, CH), 0.82 (d, J ) 6.8 Hz, 3H, CH3), 0.73
(d, J ) 6.8 Hz, 3H, CH3); MS (FAB) m/z 116 (M+), 115 ([M -
1]+). Anal. Calcd for C5H12N2O: C, 51.70; H, 10.41; N, 24.12.
Found: C, 51.73; H, 10.52; N, 24.02.
L-Valine 3k as a white solid: 1.2 h (47%); ee 34% (HPLC
analysis of the corresponding N-benzoylated compound); mp 210
°C dec [lit.24 mp 298 °C dec, DL-valine]; IR (KBr) 2585-3164,
1595 cm-1; 1H NMR (D2O) δ 3.48 (d, J ) 4.4 Hz, 1H, CH), 2.13-
2.16 (m, 1H), 0.91 (d, J ) 7.0 Hz, 3H, CH3), 0.85 (d, J ) 7.0 Hz,
3H, CH3).
D
D
HCl)]; ee 96% (HPLC); mp 248-249 °C [lit.15 mp 246 °C]; IR
(KBr) 2508-3043, 1615 cm-1; 1H NMR (D2O) δ 7.13 (d, J ) 8.7
Hz, 2H, ArH), 6.78 (d, J ) 8.7 Hz, 2H, ArH), 4.87 (s, 1H, CH),
3.56 (s, 3H, CH3O).
En zym a tic Hyd r olysis of DL-3-Meth oxyp h en ylglycin e
Nitr ile (1g). D-(-)-3-Methoxyphenylglycine amide (2g) as white
powder: 1.5 h (47%); [R]25 -64 (c 0.5, MeOH); ee 77% (HPLC);
D
mp 85 °C; IR (KBr) 3382, 3348, 3326, 3284, 1674 cm-1; 1H NMR
(DMSO-d6) δ 7.47 (s, 1H, CONHH), 7.21 (t, J ) 7.7 Hz, 1H, ArH),
7.02 (s, 1H, CONHH), 6.97 (s, 1H, ArH), 6.95 (d, J ) 7.7 Hz,
1H, ArH), 6.79 (d, J ) 7.7 Hz, 1H, ArH), 4.23 (s, 1H, CH), 3.73
(s, 3H, CH3O); MS (EI) m/z 136 ([M - CONH2]+, 100%). Anal.
Calcd for C9H12N2O2: C, 59.99; H, 6.71; N, 15.55. Found: C,
59.50; H, 6.78; N, 15.45.
Ch em ica l H yd r olysis of D-(-)-P h en ylglycin e Am id e
(2a ). D-(-)-Phenylglycine amide 2a (1 mmol, ee>99%) was
refluxed in hydrochloric acid solution (6 N) for 2.5 h to give, after
the workup as for L-(+)-3a , pure D-(-)-phenylglycine 4 in 99%
yield. [R]25 -121 (c 0.8, 1 N HCl) (lit.19 [R]25 -155 (c 1.0,
L-(+)-3-Methoxyphenylglycine (3g) as white powder: 1.5 h
(46%); [R]25 +176 (c 0.5, 1 N HCl) (lit.22 [R]23 -115 (c 1.0, 1 N
D
D
NH4OH), D-(-)-3-methoxyphenylglycine); ee >99% (HPLC); mp
202 °C; IR (KBr) 2607-3157, 1610 cm-1; 1H NMR (D2O) δ 7.33
(t, J ) 7.9 Hz, 1H, ArH), 6.95-6.97 (m, 3H, ArH), 4.61 (s, 1H,
CH), 3.76 (s, 3H, CH3O); MS (EI) m/z 120 ([M - CO2 - NH3]+,
100%). Anal. Calcd for C9H11N2O2: C, 59.66; H, 6.12; N, 7.73.
Found: C, 59.32; H, 6.21; N, 7.79.
D
D
1 N HCl), D-(-)-phenylglycine); ee >99% (HPLC); mp 239 °C
(lit.20 mp 246 °C).
Ack n ow led gm en t. This work was supported by the
Major Basic Research Development Program (No.
2000077506), the National Nature Science Foundation
of China, and the Chinese Academy of Sciences. M.X.W.
thanks O. Meth-Cohn and J . Colby for discussions.
En zym a tic Hyd r olysis of DL-3,4-Meth ylen ed ioxyp h en yl-
glycin e Nit r ile (1h ). D-(-)-3,4-Methylenedioxyphenylglycine
amide (2h ) as a yellowy powder: 2.2 h (39%); [R]25 -45 (c 0.4,
D
MeOH); ee >99% (HPLC); mp 128-129 °C; IR (KBr) 3381, 3309,
3293 (sh), 3013, 1665, 1653 cm-1;1H NMR (DMSO-d6) δ 7.38 (s,
1H, CONHH), 6.96 (s, 1H, CONHH), 6,93 (s, 1H, ArH), 6.82 (d,
J ) 8.0 Hz, 1H, ArH), 6.79 (d, J ) 8.0 Hz, 1H, ArH), 5.94 (s,
2H, OCH2O), 4.17 (s, 1H, CH); MS (EI) m/z 150 ([M - CONH2]+,
100%). Anal. Calcd for C9H10N2O3: C, 55.67; H, 5.19; N, 14.43.
Found: C, 55.62; H, 5.36; N, 14.28.
Su p p or tin g In for m a tion Ava ila ble: Preparation of ra-
cemic R-amino nitrile hydrochlorides 1, N-benzoylation of
valine, cyclohexylglycine, and their amides, HPLC analysis of
amino acids 3 and amides 2, and results of biotransformation
of racemic R-amino acid amides 2. This material is available
L-(-)-3,4-Methylenedioxyphenylglycine (3h ) as a yellow pow-
der: 2.2 h (48%); [R]25 +120 (c 0.4, 1 N HCl); ee 99% (HPLC);
D
J O0256282
mp 229 °C; IR (KBr) 2598-3155, 1610 cm-1; H NMR (D2O) δ
1
6.73-6.78 (m, 3H, ArH), 5.78 (s, 2H, OCH2O), 4.88 (s, 1H, CH);
MS (EI) m/z 195 (M+, 5%), 150 ([M - CO2H]+, 100). Anal. Calcd
for C9H9NO4: C, 55.39; H, 4.65; N, 7.18. Found: C, 55.29; H,
4.68; N, 7.11.
(23) Beller, M.; Eckert, M.; Geissler, H.; Napierski, B.; Rebenstock,
H.-P.; Holla, E. W. Chem.-Eur. J . 1998, 4, 935.
(24) Oversly L. B.; Ingersole, A. M. J . Am. Chem. Soc. 1951, 73,
3363.
J . Org. Chem, Vol. 67, No. 18, 2002 6545