I. L. Jones et al. / Tetrahedron Letters 48 (2007) 521–525
525
Conteras, R. J. Chem. Soc., Perkin Trans. 2 1998, 401–
406, and references cited therein.
4. (a) Dugave, C.; Demange, L. Chem. Rev. 2003, 103, 2475–
2532; (b) Clayden, J. Synlett 1998, 810–816.
drotestosterone when complexed to the androgen recep-
tor showed an interatomic distance of 10.893 A.16 In 25,
˚
the comparable distance between the hydrazone nitro-
gen and the hydroxyl group lies between 9.65 and
5. For related work using the urea motif to engender
molecular rigidity, see: Bridgeman, E.; Cavill, J. L.;
Schofield, D. J.; Wilkins, D. S.; Tomkinson, N. C. O.
Tetrahedron Lett. 2005, 46, 8521–8524.
˚
10.97 A, suggesting that the interatomic distance be-
tween the ketone and hydroxyl in mimic 24 may well
be able to demonstrate the same ligand–receptor inter-
actions displayed by 2.
1
6. All compounds were characterised by mp, IR, H NMR,
13C NMR, MS and HRMS.
In summary, we have developed two short, effective and
convenient synthetic routes to a variety of non-symmet-
rical oxamides and oxoamides. Both key coupling proce-
dures can be carried out in the presence of unprotected
alcohol groups and without the need for an aqueous
workup allowing for the reaction to be carried out in
parallel on potentially water soluble substrates. Crystal-
lographic data on the oxamide 25 has shown the dicar-
bonyl motif to preferentially adopt an antiparallel
arrangement fixing the substituents within molecular
space, which may also prove useful in the design of
pharmacophores for alternative target receptors. The
compounds reported are currently under biological eval-
uation and we will report our findings in due course.
7. Gautier, E. C. L.; Graham, A. E.; McKillop, A.; Standen,
S. P.; Taylor, R. J. K. Tetrahedron Lett. 1997, 38, 1881–
1884.
´
´
8. (a) Stolle, R. Chem. Ber. 1914, 47, 1130–1132; (b) Stolle,
R.; Knebel, E. Chem. Ber. 1921, 54, 1213–1220.
9. For a related strategy in the preparation of ureas, see:
Bridgeman, E.; Tomkinson, N. C. O. Synlett 2006, 243–
246.
´
10. (a) Temeriusz, A.; Rowinska, M.; Piekarska-Bartoszewicz,
B. Carbohydr. Res. 2005, 340, 1656–1660; (b) Temeriusz,
A.; Anulewicz, R.; Wawer, I.; Krygowski, T. M.; Pie-
´
karska-Bartoszewicz, B.; Rowinska, M. Carbohydr. Res.
2001, 334, 71–79.
11. Rastegar, M. F.; Todd, E. K.; Tang, H.; Wang, Z. Y. Org.
Lett. 2004, 6, 4519–4522.
12. Neveux, M.; Bruneau, C.; Lecolier, S.; Dixneuf, P. H.
Tetrahedron 1993, 49, 2629–2640.
13. Katritzky, A. R.; Levell, J. R.; Pleynet, D. P. M. Synthesis
1998, 153–156.
Acknowledgements
14. Mitlak, B. H.; Cohen, F. J. Drugs 1999, 57, 653–663.
15. Crystal data for 25: C15H18N6O7, crystallises from toluene
as yellow rods. Triclinic, space group P-1, a = 6.3978(4),
The authors wish to thank Dr. Timothy M. Willson
(GSK) for helpful discussions, the BBSRC (72/18337)
for financial support, and the HRMS service at Swansea
for analyses.
˚
b = 10.3825(9), c = 15.3945(13) A, a = 70.443(3), b =
3
˚
81.209(5), c = 72.370(5)°, 916.82(12) A , Z = 2, Dc = 1.428
Mg m3, M = 394.35, T = 120(2) K. 16461 Reflections
collected, 3241 independent (Rint = 0.0725) which were
used in calculations R1 = 0.1028, wR2 = 0.2712 for
References and notes
observed
unique
reflections
[F2 > 2r(F2)]
and
R1 = 0.1341, wR2 = 0.2895 for all 3241 unique reflections.
The max. and min. residual electron densities on the final
1. (a) O’Malley, B. W. Hormones and Signalling; Academic
Press: San Diego, 1998; (b)Steroid Hormone Action;
Parker, M. G., Ed.; IRL Press: Oxford, 1993.
2. (a) Saraber, F. C. E.; de Groot, A. Tetrahedron 2006, 62,
5363–5383; (b) Bijoy, P.; Naik, R. G.; Shivakumar, U.;
Rao, G. S. R. J. Ind. Inst. Sci. 1994, 74, 519–541; (c)
Zeelen, F. J. Nat. Prod. Rep. 1994, 11, 607–612; (d) Groen,
M. B.; Zeelen, F. J. Recl. Trav. Chim. Pays-Bas 1986, 105,
465–487.
À3
˚
difference Fourier map were 0.663 and À0.406 e A
,
respectively. Crystallographic data (excluding structure
factors) for structure 25 has been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary Publication Number 620459. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44 (0)1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk).
3. (a) Hoffmann, M.; Rychlewska, U.; Warzajtis, B. Cryst.
16. Pereira do Jesus-Tran, K.; Cote, P.-L.; Cantin, L.;
Blanchet, J.; Labrie, F.; Breton, R. Prot. Sci. 2006, 15,
987–999.
´
´
Eng. Commun. 2005, 7, 260–265; (b) Martınez-Martınez,
´
F. J.; Padilla-Martınez, I. I.; Brito, M. A.; Geniz, E. D.;
Rojas, R. C.; Saavedra, J. B. R.; Ho¨pfl, H.; Tlahuextl, M.;