T. K. Chakraborty et al. / Tetrahedron Letters 43 (2002) 2589–2592
2591
3. For earlier works on related topics see: (a) Jones, R. C.
F.; Ward, G. J. Tetrahedron Lett. 1988, 29, 3853–3856;
(b) Feigel, M.; Lugert, G.; Heichert, C. Liebigs Ann.
Chem. 1987, 367–373. For some leading in-depth reviews
see: (c) Recent Advances in Peptidomimetics; Tetra-
hedron Symposia-in-Print, No. 83, [Tetrahedron, 2000,
56(50)]; Aube´, J., Guest Ed.; Pergamon Press: Oxford,
UK. (d) Robinson, J. A. Synlett 2000, 429–441; (e)
Peptides and Peptidomimetics that Adopt Folded Struc-
tures; Symposia-in-Print, No. 15, [Bioorg. Med. Chem.,
1999, 7(1)]; Kelly, J. W., Guest Ed.; Pergamon Press:
Oxford, UK; (f) Hanessian, S.; McNaughton-Smith, G.;
Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53,
12789–12854; (g) Giannis, A.; Kolter, T. Angew. Chem.
Int. Ed. Engl. 1993, 32, 1244–1267.
d6, here also strong sequential NHꢀNH connectivity
can be seen across the entire length of these molecules.
However, the absence of any cross peak between
PaaNH and pyrrole C4ꢀH, unlike those seen in both 3
and 4 in DMSO-d6, can possibly be attributed to a
g-turn type structure as shown in Fig. 1 involving
intramolecular hydrogen bonding between the pyrrole
NH and the carbonyl of the previous residues,
BocCꢁO (3) or ValCꢁO (4). This is in agreement with
the known propensity of dehydroalanine (DAla) moi-
eties to adopt near planar conformations in peptides
with trans orientations for the and torsions and
induce an inverse g-turn in the preceding residue.2e
The characteristic rOe cross peaks and the small
changes of the pyrroleNH chemical shifts during the
solvent titration studies (Dl=0.3 ppm for both 3 and
4 on addition of 25% v/v of DMSO-d6) supported the
proposed g-turn structures for these molecules in the
nonpolar solvent.
4. Silverstein, R. M.; Ryskiewicz, E. E.; Willard, C. Org.
Synth. 1956, 36, 74–76.
5. Hodge, P.; Rickards, R. W. J. Chem. Soc. 1963, 2543–
2545.
6. Khan, M. K. A.; Morgan, K. J.; Morrey, O. P. Tetra-
hedron 1966, 22, 2095–2105.
7. Blanco, J. L. J.; Fernandez, J. M. G.; Gadelle, A.;
Defaye, J. Carbohydr. Res. 1997, 303, 367–372.
The rigid scaffold of the pyrrole amino acid described
here can serve as a conformationally constrained tem-
plate that may find useful application in developing
novel peptidomimetics with interesting structures and
useful properties. Further work is under progress.
8. 3: 1H NMR (DMSO-d6, 500 MHz): l 11.08 (br s, 1H,
Pyrrole NH), 8.27 (t, J=5.9 Hz, 1H, GlyNH), 7.94 (d,
J=8.5 Hz, 1H, AlaNH), 7.86 (d, J=8.5 Hz, 1H,
LeuNH), 7.09 (t, J=5.3 Hz, 1H, PaaNH), 6.74 (t, J=
2.8 Hz, 1H, PaaC3H), 5.90 (t, J=2.8 Hz, 1H, PaaC4H),
4.41 (m, 1H, AlahH), 4.33 (dt, J=6.4, 8.5, 1H, LeuhH),
4.07 (m, 2H, PaaC6H2), 3.85 (dd, J=5.9, 17.3 Hz, 1H,
GlyhH), 3.79 (dd, J=5.9, 17.3 Hz, 1H, GlyhH), 3.61 (s,
3H, OMe), 1.62 (m, 1H, LeukH), 1.48 (m, 1H, LeuiH),
1.44 (m, 1H, LeuiH%), 1.37 (s, 9H, Boc), 1.28 (d, J=7.1
Hz, 3H, AlaiH), 0.86 (d, J=6.6 Hz, 3H, LeulH), 0.82
(d, J=6.6 Hz, 3H, LeulH%).
Acknowledgements
Authors wish to thank DST, New Delhi for financial
support (T.K.C.) and CSIR, New Delhi for research
fellowships (B.K.M. and S.K.K.).
1
References
3: H NMR (CDCl3+12% DMSO-d6, 500 MHz): l 10.63
(br s, 1H, Pyrrole NH), 7.69 (t, J=5.5 Hz, 1H,
GlyNH), 7.47 (d, J=8.5 Hz, 1H, LeuNH), 7.42 (d,
J=6.4 Hz, 1H, AlaNH), 6.69 (t, J=2.9 Hz, 1H,
PaaC3H), 6.08 (bt, 1H, PaaNH), 6.02 (t, J=2.9 Hz,
1H, PaaC4H), 4.53 (m, 1H, AlahH), 4.51 (ddd, J=4.9,
8.5 and 9.8 Hz, 1H, LeuhH), 4.22 (m, 2H, PaaC6H2),
4.04 (dd, J=6.0, 17.7 Hz, 1H, GlyhH), 3.92 (dd, J=5.3,
17.7 Hz, 1H, GlyhH%), 3.71 (s, 3H, OMe), 1.72 (ddd,
J=4.9, 8.7 and 13.4 Hz, 1H, LeuiH), 1.64 (m, 1H,
LeukH), 1.54 (ddd, J=5.0, 9.9 and 13.4 Hz, 1H,
LeuiH%), 1.45 (d, J=6.3 Hz, 3H, AlaiH), 1.44 (s, 9H,
Boc), 0.91 (d, J=6.4 Hz, 3H, LeulH), 0.88 (d, J=6.4
Hz, 3H, LeulH%).
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5634–5642; (f) Uma, K.; Chauhan, V. S.; Kumar, A.;
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233–235.
4: 1H NMR (DMSO-d6, 500 MHz): l 11.17 (br s, 1H,
Pyrrole NH), 8.27 (t, J=5.9 Hz, 1H, GlyNH), 8.11 (t,
J=5.3 Hz, 1H, PaaNH), 7.89 (d, J=8.5 Hz, 1H,
LeuNH), 6.77 (t, J=2.9 Hz, 1H, PaaC3H), 6.63 (d,
J=9.0 Hz, 1H, ValNH), 5.91 (t, J=2.9 Hz, 1H,
PaaC4H), 4.51 (ddd, J=4.9, 8.5 and 10.1 Hz, 1H,
LeuhH), 4.22 (dd, J=5.6, 15.5 Hz, 1H, PaaC6H), 4.21
(dd, J=5.5, 15.5 Hz, 1H, PaaC6H%), 3.84 (dd, J=5.9,
17.3 Hz, 1H, GlyhH), 3.80 (dd, J=6.0, 17.3 Hz, 1H,
GlyhH%), 3.76 (dd, J=7.7, 9.0 Hz, 1H, ValhH), 3.60 (s,
3H, OMe), 1.64 (m, 1H, LeukH), 1.60 (ddd, J=4.9, 10.1
and 13.3 Hz, 1H, LeuiH), 1.54 (ddd, J=4.9, 9.5 and