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Volume 69 
Part 3 
Pages o419-o420  
March 2013  

Received 12 February 2013
Accepted 15 February 2013
Online 20 February 2013

Key indicators
Single-crystal X-ray study
T = 160 K
Mean [sigma](C-C) = 0.002 Å
Disorder in main residue
R = 0.042
wR = 0.103
Data-to-parameter ratio = 21.3
Details
Open access

(S)-N-[(4-{(S)-1-[2-(4-Methoxybenzamido)-2-methylpropanoyl]pyrrolidine-2-carboxamido}-3,4,5,6-tetrahydro-2H-pyran-4-yl)carbonyl]proline dimethyl sulfoxide monosolvate (4-MeBz-Aib-Pro-Thp-Pro-OH)

aInstitute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Correspondence e-mail: alinden@oci.uzh.ch

The asymmetric unit of the title compound, C28H38N4O8·C2H6OS, contains one tetrapeptide and one disordered dimethyl sulfoxide (DMSO) molecule. The central five-membered ring (Pro2) of the peptide molecule has a disordered envelope conformation [occupancy ratio 0.879 (2):0.121 (2)] with the envelope flap atom, the central C atom of the three ring methylene groups, lying on alternate sides of the mean ring plane. The terminal five-membered ring (Pro4) also adopts an envelope conformation with the C atom of the methylene group closest to the carboxylic acid function as the envelope flap, and the six-membered tetrahydropyrane ring shows a chair conformation. The tetrapeptide exists in a helical conformation, stabilized by an intramolecular hydrogen bond between the amide N-H group of the heterocyclic [alpha]-amino acid Thp and the amide O atom of the 4-methoxybenzoyl group. This interaction has a graph set motif of S(10) and serves to maintain a fairly rigid [beta]-turn structure. In the crystal, the terminal hydroxy group forms a hydrogen bond with the amide O atom of Thp of a neighbouring molecule, and the amide N-H group at the opposite end of the molecule forms a hydrogen bond with the amide O atom of Thp of another neighbouring molecule. The combination of both intermolecular interactions links the molecules into an extended three-dimensional framework.

Related literature

For the azirine/oxazolone method, see: Heimgartner (1991[Heimgartner, H. (1991). Angew. Chem. Int. Ed. Engl. 30, 238-265.]); Altherr et al. (2007[Altherr, W., Linden, A. & Heimgartner, H. (2007). Chem. Biodivers. 6, 1144-1169.]); Stamm & Heimgartner (2004[Stamm, S. & Heimgartner, H. (2004). Eur. J. Org. Chem. pp. 3820-3827.]). For the synthesis of Thp-containing peptides via the azirine/oxazolone method and their crystal structures, see: Suter et al. (2000[Suter, G., Stoykova, S. A., Linden, A. & Heimgartner, H. (2000). Helv. Chim. Acta, 83, 2961-2974.]). For the synthesis of Aib-Pro containing peptides via azirine coupling, see: Luykx et al. (2003[Luykx, R. T. N., Linden, A. & Heimgartner, H. (2003). Helv. Chim. Acta, 86, 4093-4111.]); Stamm & Heimgartner (2006[Stamm, S. & Heimgartner, H. (2006). Tetrahedron, 62, 9671-9680.]); Pradeille et al. (2012[Pradeille, N., Tzouros, M., Möhle, K., Linden, A. & Heimgartner, H. (2012). Chem. Biodivers. 9, 2528-2558.]); Stoykova et al. (2012[Stoykova, S. A., Linden, A. & Heimgartner, H. (2012). Helv. Chim. Acta, 95, 1325-1351.]). For the insertion of Xaa-Pro units (Xaa = heterocyclic [alpha]-amino carboxylic acid) into peptides, see: Suter et al. (2000[Suter, G., Stoykova, S. A., Linden, A. & Heimgartner, H. (2000). Helv. Chim. Acta, 83, 2961-2974.]); Stamm et al. (2003[Stamm, S., Linden, A. & Heimgartner, H. (2003). Helv. Chim. Acta, 86, 1371-1396.]). For the conformation of peptides containing [alpha],[alpha]-disubstituted [alpha]-amino acids, see: Prasad & Balaram (1984[Prasad, B. V. & Balaram, P. (1984). CRC Crit. Rev. Biochem. 16, 307-348.]); Toniolo & Benedetti (1991[Toniolo, C. & Benedetti, E. (1991). Macromolecules, 24, 4004-4009.]); Schweitzer-Stenner et al. (2007[Schweitzer-Stenner, R., Gonzales, W., Bourne, G. T., Feng, J. A. & Marshall, G. R. (2007). J. Am. Chem. Soc. 129, 13095-13109.]); Aravinda et al. (2008[Aravinda, S., Shamala, N. & Balaram, P. (2008). Chem. Biodivers. 5, 1238-1262.]); Demizu et al. (2012[Demizu, Y., Yabuki, Y., Doi, M., Sato, Y., Tanaka, M. & Kurikara, M. (2012). J. Pept. Sci. 18, 466-475.]). For crystal structures of peptaibols, see: Whitmore & Wallace (2004[Whitmore, L. & Wallace, B. A. (2004). Nucleic Acids Res. 32, D593-D594.]), authors of The Peptaibol Database http://www.cryst.bbk.ac.uk/peptaibol . For graph-set theory, see: Bernstein et al. (1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.]).

[Scheme 1]

Experimental

Crystal data
  • C28H38N4O8·C2H6OS

  • Mr = 636.76

  • Orthorhombic, P 21 21 21

  • a = 10.8594 (1) Å

  • b = 13.7414 (2) Å

  • c = 21.1929 (3) Å

  • V = 3162.48 (7) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.16 mm-1

  • T = 160 K

  • 0.28 × 0.20 × 0.18 mm

Data collection
  • Nonius KappaCCD area-detector diffractometer

  • 53400 measured reflections

  • 9238 independent reflections

  • 7711 reflections with I > 2[sigma](I)

  • Rint = 0.044

Refinement
  • R[F2 > 2[sigma](F2)] = 0.042

  • wR(F2) = 0.103

  • S = 1.02

  • 9231 reflections

  • 433 parameters

  • 21 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.28 e Å-3

  • [Delta][rho]min = -0.33 e Å-3

  • Absolute structure: Flack & Bernardinelli (1999[Flack, H. D. & Bernardinelli, G. (1999). Acta Cryst. A55, 908-915.], 2000[Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.]), 4115 Friedel pairs

  • Flack parameter: -0.02 (8)

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
O2-H2...O7i 0.87 (2) 1.81 (3) 2.6669 (17) 168 (2)
N6-H6...O13 0.87 (2) 2.19 (2) 3.0468 (17) 169.5 (18)
N12-H12...O4ii 0.80 (2) 2.37 (2) 3.1247 (18) 156 (2)
Symmetry codes: (i) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z]; (ii) [-x+{\script{1\over 2}}, -y+1, z+{\script{1\over 2}}].

Data collection: COLLECT (Nonius, 2000[Nonius (2000). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEPII (Johnson, 1976[Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA.]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: NC2305 ).


References

Altherr, W., Linden, A. & Heimgartner, H. (2007). Chem. Biodivers. 6, 1144-1169.  [CSD] [CrossRef]
Aravinda, S., Shamala, N. & Balaram, P. (2008). Chem. Biodivers. 5, 1238-1262.  [CrossRef] [PubMed] [ChemPort]
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.  [CrossRef] [ChemPort] [ISI]
Demizu, Y., Yabuki, Y., Doi, M., Sato, Y., Tanaka, M. & Kurikara, M. (2012). J. Pept. Sci. 18, 466-475.  [ISI] [CrossRef] [ChemPort] [PubMed]
Flack, H. D. & Bernardinelli, G. (1999). Acta Cryst. A55, 908-915.  [CrossRef] [details]
Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.  [ISI] [CrossRef] [ChemPort] [details]
Heimgartner, H. (1991). Angew. Chem. Int. Ed. Engl. 30, 238-265.  [CrossRef] [ISI]
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA.
Luykx, R. T. N., Linden, A. & Heimgartner, H. (2003). Helv. Chim. Acta, 86, 4093-4111.  [CSD] [CrossRef] [ChemPort]
Nonius (2000). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.
Pradeille, N., Tzouros, M., Möhle, K., Linden, A. & Heimgartner, H. (2012). Chem. Biodivers. 9, 2528-2558.  [CSD] [CrossRef] [ChemPort] [PubMed]
Prasad, B. V. & Balaram, P. (1984). CRC Crit. Rev. Biochem. 16, 307-348.  [ChemPort] [PubMed]
Schweitzer-Stenner, R., Gonzales, W., Bourne, G. T., Feng, J. A. & Marshall, G. R. (2007). J. Am. Chem. Soc. 129, 13095-13109.  [ISI] [PubMed] [ChemPort]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [ISI] [CrossRef] [details]
Stamm, S. & Heimgartner, H. (2004). Eur. J. Org. Chem. pp. 3820-3827.  [CrossRef]
Stamm, S. & Heimgartner, H. (2006). Tetrahedron, 62, 9671-9680.  [ISI] [CrossRef] [ChemPort]
Stamm, S., Linden, A. & Heimgartner, H. (2003). Helv. Chim. Acta, 86, 1371-1396.  [CSD] [CrossRef] [ChemPort]
Stoykova, S. A., Linden, A. & Heimgartner, H. (2012). Helv. Chim. Acta, 95, 1325-1351.  [CSD] [CrossRef] [ChemPort]
Suter, G., Stoykova, S. A., Linden, A. & Heimgartner, H. (2000). Helv. Chim. Acta, 83, 2961-2974.  [CrossRef] [ChemPort]
Toniolo, C. & Benedetti, E. (1991). Macromolecules, 24, 4004-4009.  [CrossRef] [ChemPort] [ISI]
Whitmore, L. & Wallace, B. A. (2004). Nucleic Acids Res. 32, D593-D594.  [ISI] [CrossRef] [PubMed] [ChemPort]


Acta Cryst (2013). E69, o419-o420   [ doi:10.1107/S1600536813004546 ]

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