PAPER
Synthesis of (2S,6S)-and meso-Diaminopimelic Acids
97
lution was concentrated by rotary evaporation under reduced pres-
sure. The residue was used directly without purification for the
preparation of Mosher’s amide derivative.
Acknowledgements
This work was supported by grants from the US Public Health Ser-
vice (DK 17420) and the National Institute of Drug Abuse (DA
13449). We thank Professor Dominic V. McGrath for use of his po-
larimeter.
To a solution of (R)-(+)- -methoxy- -trifluorophenylacetic acid
(61 mg, 0.26 mmol) in CH2Cl2 (2 mL) at 0 °C was added DCC (58
mg, 0.28 mmol). After 2–3 min, HOBt (48 mg, 0.35 mmol) was
added. The mixture was stirred for ca. 15 min, followed by addition
of the above amine, Et3N (49 L, 0.35 mmol) and DMAP (6 mg,
0.047 mmol). After stirring at 0 °C for 1.5 h and at r.t. for 15 h, the
white solid was filtered off. The solvent was removed to give an oil.
The oil was dissolved in EtOAc (60 mL) and the EtOAc layer was
washed with 1 N HCl (20 mL), aq sat. NaHCO3 (20 mL) and brine
(20 mL), and dried (MgSO4). Concentration of the EtOAc solution
under reduced pressure gave an oil, which was purified by flash
chromatography, eluting with EtOAc–hexanes (1:8) to provide 10
as a clear oil (112 mg, 70%); [ ]25D –19.2 (c = 0.96, CHCl3).
1H NMR (CDCl3): = 1.34–1.57 (m, 2 H), 1.44 (s, 9 H), 1.51 (s, 18
H), 1.75–2.12 (m, 4 H), 3.37 (br s, 3 H), 3.73 (s, 3 H), 4.62 (dd,
J = 2.7, 7.8 Hz, 1 H), 4.68 (dd, J = 5.1, 9.6 Hz, 1 H), 7.32 (d, J = 7.8
Hz, 1 H), 7.38–7.42 (m, 3 H). 7.53–7.56 (m, 2 H).
13C NMR (CDCl3): = 22.4, 28.1, 28.2, 29.0, 31.8, 52.4, 52.6, 55.1,
58.7, 81.4, 83.0, 84.3 (q, JC,F = 26.1 Hz), 124.0 (q, JC,F = 287.4 Hz),
128.2, 128.7, 129.7, 132.1, 152.7, 166.3, 169.8, 172.3.
References
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19F NMR (CDCl3/CFCl3): = –70.21.
HRMS (FAB): m/z calcd for C32H48F3N2O10 677.3261. Found
677.3267.
(12) Davis, F. A.; Srirajan, V. J. Org. Chem. 2000, 65, 3248.
(13) Paradisi, F.; Porzi, G.; Rinaldi, S.; Sandri, S. Tetrahedron:
Asymmetry 2000, 11, 1259.
Methyl (2R)-{[(R)-(+)- -Methoxyl- -trifluoromethylphenyl-
acetyl]amino}-(6S)-[bis(tert-butoxycarbonyl)amino]-7-(tert-
butoxycarbonyl)heptanoate (11)
In a similar manner to the synthesis of 10, compound 9 (215 mg,
0.36 mmol) gave 11 (159 mg, 65%) as a clear oil; [ ]25D –11.6 (c =
1.09, CHCl3).
1H NMR (CDCl3): = 1.20–1.34 (m, 2 H), 1.44 (s, 9 H), 1.49 (s, 18
H), 1.61–2.08 (m, 4 H), 3.51 (s, 3 H), 3.75 (s, 3 H), 4.59–4.66 (m, 2
H), 7.12 (d, J = 8.1 Hz, 1 H), 7.40–7.45 (m, 3 H), 7.53–7.56 (m, 2
H).
13C NMR (CDCl3): = 22.5, 28.1, 28.2, 29.1, 32.0, 52.2, 52.7, 55.4,
58.7, 81.5, 83.0, 84.1 (q, JC,F = 26.0 Hz), 123.8 (q, JC,F = 288.4 Hz),
127.6, 128.8, 129.7, 132.9, 152.6, 166.5, 169.7, 172.3.
(14) Hruby, V. J. Life Sci. 1982, 31, 189.
(15) Hruby, V. J.; Li, G.; Haskell-Luevano, C.; Shenderovich, M.
Biopolymers (Peptide Science) 1997, 43, 219.
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Tetrahedron 1997, 53, 16645.
(17) Lin, J.; Liao, S.; Han, Y.; Qiu, W.; Hruby, V. J. Tetrahedron:
Asymmetry 1997, 8, 3213.
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Tetrahedron 2000, 56, 2577.
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Asymmetry 1999, 10, 4265.
19F NMR (CDCl3/CFCl3): = –69.96.
(21) Soloshonok, V. A.; Cai, C.; Hruby, V. J.; Van Meervelt, L.;
Mischenko, N. Tetrahedron 1999, 55, 12031.
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Tetrahedron 1999, 55, 12045.
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Intl. Publ. Ltd.: Copenhagen, 1998, 51-62.
HRMS (FAB): m/z calcd for C32H48F3N2O10 677.3261. Found
677.3270.
(2S, 6S)-(+)-Diaminopimelic Acid (1)
A mixture of 8 (260 mg, 0.44 mmol) in 30% HBr in AcOH (15 mL)
and phenol (70 mg) was refluxed for 15 h. The mixture was cooled
to 0 °C with an ice bath, and was washed with Et2O (20 mL). The
solution was concentrated to ca. 2 mL, and then was loaded on to a
Dowex ion-exchange resin and eluted with H2O (90 mL) followed
by aq 10% NH4OH solution (250 mL) to give 41 mg (53%) of 1;
[ ]25 +41.4 (c = 0.98, 1 N HCl) {Lit.12 [ ]23D +42.7 (c = 1.1, 1 N
D
HCl)}.
1H NMR (D2O): = 1.24–1.33 (m, 2 H), 1.52–1.80 (m, 4 H), 3.52–
3.61 (m, 2 H).
meso-(2S, 6R)-Diaminopimelic Acid (2)
In a similar manner as for the synthesis of 1, compound 9 (340 mg,
0.57 mmol) in 30% HBr in AcOH and phenol (91 mg) gave 2 (62
mg, 62%) after purification.12
1H NMR (D2O): = 1.33–1.54 (m, 2 H), 1.71–1.90 (m, 4 H), 3.88–
3.92 (m, 2 H).
(27) Hruby, V. J.; Balse, P. M. Curr. Med. Chem. 2000, 7, 945.
(28) Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J.
Am. Soc. Chem. 1993, 115, 10125.
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Lee, J. R.; Martinez, J. P. Pure Appl. Chem. 1996, 68, 37.
(30) Burk, M. J. Acc. Chem. Res. 2000, 33, 363.
Synthesis 2002, No. 1, 94–98 ISSN 0039-7881 © Thieme Stuttgart · New York