F. J. Sayago et al. / Tetrahedron: Asymmetry 18 (2007) 2358–2364
2363
Haskell-Luevano, C.; Shenderovich, M. Biopolymers (Pept.
Sci.) 1997, 43, 219–266; (e) Rizo, J.; Gierasch, L. M. Annu.
Rev. Biochem. 1992, 61, 387–418.
Spectroscopic data for (R,R,R)- and (S,S,S)-4 are identical
to those given above for the racemic compound.
3. (a) Karoyan, P.; Sagan, S.; Lequin, O.; Quancard, J.;
Lavielle, S.; Chassaing, G. Substituted Prolines: Syntheses
and Applications in Structure–Activity Relationship Studies
of Biologically Active Peptides. In Targets in Heterocyclic
Systems. Chemistry and Properties; Attanasi, O. A., Spinelli,
D., Eds.; Royal Society of Chemistry: Cambridge, 2005; Vol.
4.8. Synthesis of (2R,3aR,7aR)-N-(tert-butoxycarbonyl)-
octahydroindole-2-carboxylic acid, (R,R,R)-5
A solution of (R,R,R)-4 (2.28 g, 6.35 mmol) in ethyl acetate
(50 mL) was hydrogenated at room temperature in the
presence of 10% palladium–carbon (230 mg). After 18 h,
filtration of the catalyst and evaporation of the solvent
afforded pure (R,R,R)-5 as a white solid (1.70 g, 6.32 mmol,
100% yield). Mp 134–136 ꢂC. [a]D = +22.6 (c 0.50,
´
8, pp 216–273; (b) Cativiela, C.; Dıaz-de-Villegas, M. D.
Tetrahedron: Asymmetry 2000, 11, 645–732.
4. (a) Reiersen, H.; Rees, A. R. Trends Biochem. Sci. 2001, 26,
679–684; (b) Vanhoof, G.; Goossens, F.; De Meester, I.;
MeOH). IR (Nujol) m 3600–2500, 1695 cmꢀ1 1H NMR
.
´
Hendriks, D.; Scharpe, S. FASEB J. 1995, 9, 736–744; (c)
MacArthur, M. W.; Thornton, J. M. J. Mol. Biol. 1991, 218,
397–412.
(DMSO-d6, 400 MHz) d 12.49 (br s, 1H), 4.03 (m, 1H),
3.63 (m, 1H), 2.24 (m, 1H), 2.06 (m, 1H), 1.95–1.76 (m,
2H), 1.67–1.52 (m, 3H), 1.43–1.01 (m, 4H), overlapped
with 1.37 and 1.32 (each s, 9H). 13C NMR (DMSO-d6,
100 MHz) d (duplicate signals are observed for most car-
bons) 174.55, 174.00; 153.02, 152.44; 78.35, 78.30; 58.77,
58.48; 56.84, 56.35; 36.22, 35.65; 31.67, 31.01; 28.09,
27.90; 27.54, 27.01; 25.26; 23.29, 23.17; 20.07, 20.04.
HRMS (ESI neg.) C14H22NO4 [MꢀH]ꢀ: calcd 268.1554,
found 268.1555.
5. (a) Alfakih, K.; Hall, A. S. Expert Opin. Pharmacother. 2006,
7, 63–71; (b) Menard, J.; Patchett, A. A. Adv. Protein Chem.
2001, 56, 13–75; (c) Hurst, M.; Jarvis, B. Drugs 2001, 61, 867–
896; (d) Todd, P. A.; Fitton, A. Drugs 1991, 42, 90–114.
6. (a) Curran, M. P.; McCormack, P. L.; Simpson, D. Drugs
2006, 66, 235–255; (b) ASCOT Investigators Lancet 2005,
366, 895–906; (c) PROGRESS Collaborative Group Lancet
2001, 358, 1033–1041.
7. (a) Gass, J.; Khosla, C. Cell. Mol. Life Sci. 2007, 64, 345–355;
´
(b) Brandt, I.; Scharpe, S.; Lambeir, A.-M. Clin. Chim. Acta.
´
2007, 377, 50–61; (c) Garcıa-Horsman, J. A.; Ma¨nnisto¨, P. T.;
4.9. Synthesis of (2S,3aS,7aS)-N-(tert-butoxycarbonyl)-
octahydroindole-2-carboxylic acid, (S,S,S)-5
Vena¨la¨inen, J. I. Neuropeptides 2007, 41, 1–24; (d) Rosen-
blum, J. S.; Kozarich, J. W. Curr. Opin. Chem. Biol. 2003, 7,
´
496–504; (e) Polgar, L. Cell. Mol. Life Sci. 2002, 59, 349–362.
An identical procedure to that described above was applied
to transform (S,S,S)-4 (2.28 g, 6.35 mmol) into (S,S,S)-5
`
´
8. (a) Bellemere, G.; Vaudry, H.; Morain, P.; Jegou, S. J.
Neuroendocrinol. 2005, 17, 306–313; (b) Schneider, J. S.;
Giardiniere, M.; Morain, P. Neuropsychopharmacology 2002,
26, 176–182; (c) Morain, P.; Lestage, P.; De Nanteuil, G.;
Jochemsen, R.; Robin, J. L.; Guez, D.; Boyer, P. A. CNS
Drug Rev. 2002, 8, 31–52; (d) Morain, P.; Robin, J. L.; De
Nanteuil, G.; Jochemsen, R.; Heidet, V.; Guez, D. Br. J. Clin.
Pharmacol. 2000, 50, 350–359; (e) Barelli, H.; Petit, A.;
Hirsch, E.; Wilk, S.; De Nanteuil, G.; Morain, P.; Checler, F.
Biochem. Biophys. Res. Commun. 1999, 257, 657–661; (f)
(1.71 g, 6.34 mmol, 100% yield). Mp 134–136 ꢂC. [a]D
=
ꢀ23.2 (c 0.50, MeOH).21 HRMS (ESI neg.) C14H22NO4
[MꢀH]ꢀ: calcd 268.1554, found 268.1549. Spectroscopic
data are the same as those described for (R,R,R)-5.
Acknowledgements
´
´
Portevin, B.; Benoist, A.; Remond, G.; Herve, Y.; Vincent,
M.; Lepagnol, J.; De Nanteuil, G. J. Med. Chem. 1996, 39,
2379–2391.
´
Financial support from the Ministerio de Educacion y
Ciencia–FEDER (Project CTQ2004-5358) and Gobierno
de Aragon (Project PIP206/2005 and research group E40)
´
9. (a) Stewart, J. M. Peptides 2004, 25, 527–532; (b) Reissmann,
S.; Imhof, D. Curr. Med. Chem. 2004, 11, 2823–2844; (c)
Regoli, D.; Allogho, S. N.; Rizzi, A.; Gobeil, F. J. Eur. J.
Pharmacol. 1998, 348, 1–10.
is gratefully acknowledged. The authors thank Ana Lidia
Bernad for technical assistance with HPLC. This project
has been funded in whole or in part with Federal funds
from the National Cancer Institute, National Institutes of
Health, under contract number NO1-CO-12400. The con-
tent of this publication does not necessarily reflect the view
of the policies of the Department of Health and Human
Services, nor does mention of trade names, commercial
products, or organization imply endorsement by the US
Government. This research was supported (in part) by
the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research.
10. (a) Bas, M.; Bier, H.; Greve, J.; Kojda, G.; Hoffmann, T. K.
Allergy 2006, 61, 1490–1492; (b) Sorbera, L. A.; Fernandez-
Forner, D.; Bayes, M. Drug Future 2006, 31, 101–106; (c)
Abraham, W. M.; Scuri, M.; Farmer, S. G. Eur. J. Pharma-
col. 2006, 533, 215–221; (d) Akbary, A. M.; Wirth, K. J.;
Scholkens, B. A. Immunopharmacology 1996, 33, 238–242; (e)
Griesbacher, T.; Lembeck, F. Br. J. Pharmacol. 1992, 107,
356–360; (f) Wirth, K.; Hock, F. J.; Albus, U.; Linz, W.;
Alpermann, H. G.; Anagnostopoulos, H.; Henke, S.; Bre-
ipohl, G.; Konig, W.; Knolle, J.; Scholkens, B. A. Br. J.
Pharmacol. 1991, 102, 774–777.
11. (a) Enantioselective Organocatalysis: Reactions and Experi-
mental Procedures; Dalko, P. I., Ed.; Wiley-VCH: Weinheim,
2007; (b) Berkessel, A.; Gro¨ger, H. Asymmetric Organocatal-
ysis; Wiley-VCH: Weinheim, 2005; (c) Dalko, P. I.; Moisan,
L. Angew. Chem., Int. Ed. 2004, 43, 5138–5175.
References
1. Handbook of Biologically Active Peptides; Kastin, A. J., Ed.;
Academic Press, Elsevier: London, 2006.
12. It should be noted that this nomenclature is ambiguous since
all four Oic stereoisomers having an (S) configuration at the a
carbon can actually be denoted as L. However, in the text,
L-Oic is always used in reference to the (2S,3aS,7aS)
compound.
2. (a) Cowell, S. M.; Lee, Y. S.; Cain, J. P.; Hruby, V. J. Curr.
Med. Chem. 2004, 11, 2785–2798; (b) Sagan, S.; Karoyan, P.;
Lequin, O.; Chassaing, G.; Lavielle, S. Curr. Med. Chem.
2004, 11, 2799–2822; (c) Gibson, S. E.; Guillo, N.; Tozer, M.
J. Tetrahedron 1999, 55, 585–615; (d) Hruby, V. J.; Li, G.;