W. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 1769–1774
1773
with HCl. As a result, (R)-nifenalol hydrochloride was pro-
duced as a white solid.
3.02 (dd, 1H, J1 = 12.2 Hz, J2 = 3.7 Hz), 4.76 (dd, 1H,
J1 = 9.0 Hz, J2 = 3.6 Hz), 7.55 (d, 2H, J = 8.6 Hz), 8.21
(d, 2H, J = 8.7 Hz).
4.4. Spectral data for the biosynthesized compounds
15
(R)-Nifenalol hydrochloride ½aꢁD ¼ ꢀ41:5 (c 0.286, H2O)
15
25
Compound 1b. ½aꢁD ¼ ꢀ59:2 (c 0.658, CHCl3) {lit.15
{lit.34 ½aꢁD ¼ ꢀ40:3 (c 1.07, H2O)}.
25
½aꢁD ¼ ꢀ55:1 (c 1.63, CHCl3), S}. 1H NMR (500 MHz,
25
CDCl3): d 1.53 (d, 3H, J = 6.4 Hz), 4.85 (dd, 1H,
J1 = 12.9 Hz, J2 = 6.5 Hz), 7.24–7.36 (m, 5H).
Compound 12b. ½aꢁD ¼ ꢀ25:0 (c 1.39, CHCl3) {lit.26
25
½aꢁD ¼ ꢀ27:6 (c 0.712, CHCl3), 95% ee, S}. 1H NMR
(500 MHz, CDCl3): d 1.50 (d, 3H, J = 6.7 Hz), 4.89 (dd,
1H, J1 = 13.1 Hz, J2 = 6.5 Hz), 7.18 (dd, 1H, J1 = 7.3 Hz,
J2 = 5.2 Hz), 7.28 (d, 1H, J = 7.9 Hz), 7.65–7.72 (m, 1H),
8.54 (d, 1H, J = 4.7 Hz).
25
Compound 2b. ½aꢁD ¼ ꢀ30:5 (c 1.083, EtOH) {lit.3
25
½aꢁD ¼ ꢀ29:7 (c 2.59, EtOH), S}. 1H NMR (500 MHz,
CDCl3): d 1.50 (d, 3H, J = 6.5 Hz), 5.02 (dd, 1H,
J1 = 12.9 Hz, J2 = 6.5 Hz), 7.59 (d, 2H, J = 8.6 Hz), 8.18
(d, 2H, J = 8.6 Hz).
20
Compound 13b. ½aꢁD ¼ ꢀ47:0 (c 0.625, MeOH) {lit.26
25
½aꢁD ¼ ꢀ37:2 (c 1.01, MeOH), 89% ee, S}. 1H NMR
25
Compound 3b. ½aꢁD ¼ ꢀ36:0 (c 0.775, CHCl3) {lit.15
(500 MHz, CDCl3): d 1.50 (d, 3H, J = 6.3 Hz), 4.93 (m,
1H), 7.27 (t, 1H, J = 6.2 Hz), 7.74 (d, 1H, J = 7.8 Hz),
8.42 (d, 1H, J = 4.6 Hz), 8.53 (s, 1H).
25
½aꢁD ¼ ꢀ37:9 (c 1.13, CHCl3), S}. 1H NMR (500 MHz,
CDCl3): d 1.40 (d, 3H, J = 6.2 Hz), 4.86 (dd, 1H,
J1 = 12.9 Hz, J2 = 6.4 Hz), 7.23 (d, 2H, J = 8.4 Hz), 7.46
(d, 2H, J = 8.3 Hz).
20
Compound 14b. ½aꢁD ¼ ꢀ44:0 (c 1.03, MeOH) {lit.26
25
½aꢁD ¼ ꢀ39:0 (c 0.82, MeOH), 92% ee, S}. 1H NMR
25
Compound 4b. ½aꢁD ¼ ꢀ47:8 (c 0.758, Et2O) {lit.15
(500 MHz, CDCl3): d 1.47 (d, 3H, J = 6.7 Hz), 4.88 (dd,
1H, J1 = 13.1 Hz, J2 = 6.5 Hz), 7.31 (d, 2H, J = 5.9 Hz),
8.49 (d, 2H, J = 4.4 Hz).
25
½aꢁD ¼ ꢀ49:0 (c 1.84, Et2O), S} 1H NMR (500 MHz,
CDCl3): d 1.43 (d, 3H, J = 6.5 Hz), 4.82 (d, 1H,
J = 6.5 Hz), 7.28 (dd, 4H, J1 = 16.2 Hz, J2 = 8.4 Hz).
20
Compound 15b. ½aꢁD ¼ ꢀ124:8 (c 0.8, MeOH) {lit.32
25
25
Compound 5b. ½aꢁD ¼ ꢀ56:4 (c 0.442, CHCl3) {lit.15
½aꢁD ¼ ꢀ144:0 (c 1, MeOH), R}.
25
1
½aꢁD ¼ ꢀ51:9 (c 0.718, CHCl3), S}. H NMR (500 MHz,
CDCl3): d 1.43 (d, 3H, J = 5.5 Hz), 3.75 (s, 3H), 4.75 (d,
1H, J = 5.6 Hz), 6.83 (d, 2H, J = 7.4 Hz), 7.25 (d, 2H,
J = 7.3 Hz).
1
Compound 16b. H NMR (500 MHz, CDCl3): d 1.22 (t,
3H, J = 7.3 Hz), 2.36 (s, 3H), 4.09–4.32 (m, 2H), 5.13 (s,
1H), 7.20 (d, 4H, 5.9 Hz).
1
Compound 6b. 1H NMR (500 MHz, CDCl3): d 1.46 (d, 3H,
6.5 Hz), 2.16 (br, 3H), 4.87 (q, 1H, J1 = 12.9, J2 = 6.4 Hz),
7.31 (d, 2H, 8.4 Hz), 7.46 (d, 2H, 8.4 Hz).
Compound 17b. H NMR (500 MHz, CDCl3): d 1.10 (d,
3H, J = 6 Hz), 1.27 (d, 3H, J = 6.6 Hz), 3.48 (br d, 1H,
J = 6.9 Hz), 5.05–5.20 (m, 2H), 7.23–7.48 (m, 5H).
25
1
Compound 7b. ½aꢁD ¼ ꢀ39:5 (c 0.592, CHCl3) {lit.24
Compound 18b. H NMR (500 MHz, CDCl3): d (s, 9H),
25
½aꢁD ¼ þ34:9 (c 1.0, CHCl3), 89% ee, S}. 1H NMR
5.03 (s, 1H), 7.28–7.45 (m, 5H).
(500 MHz, CDCl3): d 3.52 (t, 1H, J = 9.6 Hz), 3.62 (dd,
1H, J1 = 10.5 Hz, J2 = 3.3 Hz), 4.89 (dd, 1H, J1 = 8.9 Hz,
J2 = 3.2 Hz), 7.30–7.39 (m, 5H).
15
Compound 19b. ½aꢁD ¼ ꢀ52:7 (c 1.0, CHCl3) {lit.33
27
½aꢁD þ 36:7 (c 1.38, CHCl3), 72% ee R}.
25
25
Compound 8b. ½aꢁD ¼ ꢀ50:7 (c 0.225, cyclohexane) {lit.15
Compound 20b. ½aꢁD ¼ þ22:2 (c 0.442, CHCl3) {lit.14
25
25
1
½aꢁD ¼ ꢀ50:4 (c 1.78, cyclohexane), 98% ee, R}. H NMR
(500 MHz, CDCl3): d 3.62–3.67 (m, 1H), 3.71–3.77 (m,
1H), 4.87–4.92 (m, 1H), 7.32–7.40 (m, 5H).
½aꢁD þ 32:8 (c 3.0, CHCl3), 95% ee S}.
25
Compound 21b. ½aꢁD ¼ ꢀ11:4 (c 1.59, CHCl3) {lit.14
25
½aꢁD ꢀ 19:9 (c 3.8, CHCl3), 90% ee S}. 1H NMR
25
Compound 9b. ½aꢁD ¼ ꢀ50:8 (c 1.03, CHCl3) {lit.15
(500 MHz, CDCl3): d 1.28 (t, 3H, J = 7.1 Hz), 2.58–2.68
(m, 2H), 3.58–3.65 (m, 2H), 4.19 (dd, 2H, J1 = 14.3 Hz,
J2 = 7.2 Hz), 4.27 (m, 1H).
25
1
½aꢁD ¼ ꢀ47:2 (c 0.643, CHCl3), S}. H NMR (500 MHz,
CDCl3): d 0.92 (t, 3H, J = 7.5 Hz), 1.70–1.87 (m, 2H),
4.59 (t, 1H, J = 6.6 Hz), 7.23–7.37 (m, 5H).
15
Compound 11b. ½aꢁD ¼ ꢀ35:4 (c 0.942, CHCl3) {lit.24
Acknowledgements
25
½aꢁD ¼ þ32:1 (c 1.0, CHCl3), 91% ee, S}. 1H NMR
(500 MHz, CDCl3): d 2.82 (d, 1H, J = 3.0 Hz), 3.47–3.72
(m, 2H), 5.03 (dd, 1H, J1 = 5.3 Hz, J2 = 3.1 Hz), 7.58 (d,
2H, J = 8.6 Hz), 8.24 (d, 2H, 8.6 Hz).
This research was financially supported by the National
Natural Science Foundation of China (Nos. 20506037 &
203900506), Ministry of Science and Technology (No.
2003CB716008), and Ministry of Education, PR China
(No. 20050251011). The authors are grateful to Mr.
Guang-Yin Wang, for his chemical bestowal and technical
assistance.
1
Compound 11c. ESI-MS m/z: 226 (M+2), 225 (M+1). H
NMR (500 MHz, CDCl3): d 1.12 (t, 6H, J = 6.2 Hz), 2.60
(dd, 1H, J1 = 12.4 Hz, J2 = 9.0 Hz), 2.83–2.90 (m, 1H),