716
G. Panda, N. V. Rao
LETTER
(m, 1 H). 13C NMR (100 MHz, CDCl3): d = 169.6, 156.2,
151.3, 144.1, 144.0, 141.9, 130.5, 128.6, 128.1, 127.5,
127.4, 125.5, 120.5, 120.3, 108.3, 68.0, 67.7, 62.8, 62.4,
52.6, 51.6, 47.4. MS: m/z = 395 [M+]. Anal. Calcd: C, 60.75;
H, 5.35; N, 17.71. Found: C, 61.01; H, 5.21; N, 17.88.
Typical Procedure for Hydrolysis of 5c: To a solution of
azide 5c (75 mg, 0.189 mmol) in THF (3mL) and H2O (1
mL) were added LiOH (7 mg, 0.283 mmol) and H2O2 (0.1
mL, 1.51 mmol) and the reaction mixture was stirred at 0 °C
for 8 h. The mixture was quenched by sat. solution of
Na2SO3 at 0 °C and THF was removed in vacuo. CH2Cl2 was
added to remove any unchanged starting material. The
aqueous phase was acidified with NH4Cl and extracted twice
with EtOAc. The crude acid 1c was obtained which was
purified through column chromatography (58 mg, 88%).
(12) Typical Procedure for DIBAL-H Reduction: To a solution of
5a,b (Boc dervative; 110 mg, 0.402 mmol, Cbz dervative
155 mg, 504 mmol) in anhyd THF (5 mL) at –78 °C was
added DIBAL-H (0.68 mL for Boc, 0.85 mL for Cbz) and
the reaction micture was stirred for 1 h. The reaction mixture
was quenched with sat. NH4Cl and extracted with EtOAc.
Column chromatography over silica gel furnished 6a (50
mg, 50%) and 6b (72 mg, 50%). Spectral data: 4a: 1H NMR:
d = 5.8 (br s, 1 H), 4.8 (br s, 1 H), 3.8 (m, 1 H), 3.7 (br s, 2
H), 3.3 (s, 3 H), 2.9 (s, 3 H), 1.4 (s, 9 H). MS: m/z = 248
[M+]. Anal. Calcd; C, 48.38; H, 8.12; N, 11.28. Found: C,
49.00; H, 9.00; N, 10.28. 5a: [a]D25 = +2.9 (c = 1.0, EtOAc).
1H NMR: d = 5.1 (br s, 1 H), 4.9 (br s, 1 H), 3.9 (m, 1 H), 3.1
(m, 2 H), 3.2 (s, 3 H), 3.0 (s, 3 H), 1.4 (s, 9 H). 13C NMR:
d = 169.9, 155.5, 80.5, 61.2, 61.0, 52.7, 51.0, 32.5, 28.6 MS:
m/z = 273 [M+]. Anal. Calcd for C, 43.95; H, 7.01; N, 25.63.
Found: C, 44.00; H, 7.89; N, 24.96. 6a: [a]D25 = +12.0 (c =
1.0, EtOAc). 1H NMR: d = 9.0 (s, 1 H), 6.2 (m, 1 H), 5.2 (s,
2 H), 1.4 (s, 9 H). MS: m/z = 214 [M+]. 9b: 1H NMR: d = 8.0
(s, 1 H), 7.4–7.2 (m, 5 H), 5.1 (br s, 2 H), 3.8 (m, 1 H), 3.7
(s, 2 H), 3.2 (s, 3 H), 3.0 (s, 3 H). MS: m/z = 282 [M+]. Anal.
Calcd: C, 44.85; H, 6.59; N, 26.15. Found: C, 44.0; H, 7.00;
N, 26.10. 5b: [a]D25 = +0.3 (c = 1.0, EtOAc). 1H NMR: d =
7.4–7.2 (m, 5 H), 6.0 (br s, 1 H), 5.1 (br s, 2 H), 4.9 (m, 1 H),
3.8 (s, 3 H), 3.5 (d, J1 = 6 Hz, J2 = 2 Hz, 2 H), 3.1 (s, 3 H).
13C NMR: d = 169.9, 156.2, 136.54, 128.9, 128.5, 128.4,
67.4, 62.7, 62.5, 52.5, 51.5, 32.5. MS: m/z = 307 [M+]. Anal.
Calcd: C, 50.81; H, 5.58; N, 22.79. Found: C, 51.01; H, 5.68;
N, 22.99. 1b: [a]D25 = +9.0 (c = 1.0, EtOAc). 1H NMR: d =
7.4–7.2 (m, 5 H), 6.9 (br s, 1 H), 5.1 (m, 2 H), 4.0 (br s, 1 H),
3.8 (m, 2 H). MS: m/z = 264 [M+]. Anal. Calcd: C, 50.00; H,
4.58; N, 21.20. Found: C, 50.89; H, 4.78; N, 21.55. 6b:
[a]D25 = +8.8 (c = 1.0, EtOAc). 1H NMR: d = 9.0 (s, 1 H),
7.4–7.2 (m, 5 H), 7.1 (m, 1 H), 6.4 (s, 1 H), 5.6 (s, 1 H), 5.1
(s, 2 H). MS: m/z = 248 [M+]. Anal. Calcd: C, 53.22; H, 4.87;
N, 22.57. Found: C, 53.99; H, 4.99; N, 23.99. 4c: 1H NMR:
d = 7.7 (d, J = 8 Hz, 2 H), 7.5 (d, J = 8 Hz, 2 H), 7.4 (d, J =
8 Hz, 2 H), 7.2 (d, J = 7.8 Hz, 2 H), 6.1 (br s, 1 H), 5.8 (br s,
1 H), 4.3 (s, 2 H), 4.2 (m, 1 H), 3.8 (m, 1 H), 3.7 (m, 2 H),
3.2 (s, 3 H), 2.9 (s, 3 H). 13C NMR: d = 163.1, 156.9, 144.2,
144.1, 141.6, 141.5, 128.8, 128.1, 127.4, 125.5, 125.2,
120.3, 67.5, 63.5, 62.0, 53.3, 47.5, 39.0, 36.9, 34.2, 32.5,
31.8. MS: m/z = 370 [M+]. Anal. Calcd: C, 64.85; H, 5.99; N,
7.56. Found: C, 64.00; H, 6.99; N, 8.89.
References
(1) Present Address: Medicinal Chemistry Division, Central
Drug Research Institute, Lucknow 226001, UP, India, e-
mail: gautam_panda@lycos.com.
(2) (a) Chemistry and Biochemistry of the Amino Acids; Barett,
G. C., Ed.; Chapman and Hall: London, 1985. (b) Wagner,
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(c) Evans, C. S.; Qureshi, M. Y.; Bell, E. A. Phytochemistry
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Alper, H.; Bourque, S. C.; Manzer, L. E. J. Org. Chem. 2000,
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(f) Coppola, G. M.; Schuster, H. F. Asymmetric Synthesis,
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(6) Williams, R. M. Synthesis of Optically Active a-Amino
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(7) Schollkopf, U. Top. Curr. Chem. 1983, 109, 66.
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(11) Typical Procedure for Mitsunobu Reaction: A mixture of
Fmoc-Ser-Weinreb amide ester 4c (2.01 g, 5.4 mmol) and
Ph3P (2.13 g, 8.1mmol) in anhyd THF (120 mL) was cooled
in an ice bath. A solution of DEAD (1.46 g, 8.1 mmol) in
THF (18 mL) was added dropwise. After mixing of the
solution for 5 min, a HN3–toluene solution (8.7 mL, 16.2
mmol) was slowly added. The mixture was allowed to warm
to r.t. and stirred for 8 h. The solvent was removed in vacuo.
The oily residue was purified by column chromatography
(hexane–EtOAc, 1:1) to provide product 5c (2.0 g, 93%).
[a]D25 = +12.50 (c = 1.0, EtOAc). 1H NMR (400 MHz,
CDCl3): d = 7.7 (d, J = 8 Hz, 2 H), 7.5 (d, J = 8 Hz, 2 H), 7.4
(d, J = 8 Hz, 2 H), 7.2 (d, J = 7.8 Hz, 2 H), 6.1 (br s, 1 H),
5.0 (br s, 1 H), 4.4 (m, 3 H), 4.2 (m, 2 H), 3.8 (s, 3 H), 3.6
Synlett 2004, No. 4, 714–716 © Thieme Stuttgart · New York