(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)

Stoykova, S.A.; Linden, A.; Heimgartner, H.

doi:10.1107/S1600536813004546

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 (C-C) = 0.002 Å
Disorder in main residue
R = 0.042
wR = 0.103
Data-to-parameter ratio = 21.3
Details

(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)

Svetlana A. Stoykova,^a Anthony Linden ^a ^* and Heinz Heimgartner ^a

^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); Altherr et al. (2007); Stamm & Heimgartner (2004). For the synthesis of Thp-containing peptides via the azirine/oxazolone method and their crystal structures, see: Suter et al. (2000). For the synthesis of Aib-Pro containing peptides via azirine coupling, see: Luykx et al. (2003); Stamm & Heimgartner (2006); Pradeille et al. (2012); Stoykova et al. (2012). For the insertion of Xaa-Pro units (Xaa = heterocyclic [alpha] -amino carboxylic acid) into peptides, see: Suter et al. (2000); Stamm et al. (2003). For the conformation of peptides containing [alpha] , [alpha] -disubstituted [alpha] -amino acids, see: Prasad & Balaram (1984); Toniolo & Benedetti (1991); Schweitzer-Stenner et al. (2007); Aravinda et al. (2008); Demizu et al. (2012). For crystal structures of peptaibols, see: Whitmore & Wallace (2004), authors of The Peptaibol Database http://www.cryst.bbk.ac.uk/peptaibol . For graph-set theory, see: Bernstein et al. (1995).

Experimental

Crystal data

C₂₈H₃₈N₄O₈·C₂H₆OS
M_r = 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 radiation
= 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(I)
R_int = 0.044

Refinement

R[F² > 2(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
_max = 0.28 e Å^-3
_min = -0.33 e Å^-3
Absolute structure: Flack & Bernardinelli (1999, 2000), 4115 Friedel pairs
Flack parameter: -0.02 (8)

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
O2-H2O7ⁱ	0.87 (2)	1.81 (3)	2.6669 (17)	168 (2)
N6-H6O13	0.87 (2)	2.19 (2)	3.0468 (17)	169.5 (18)
N12-H12O4ⁱⁱ	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); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009).

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

References

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Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.
Demizu, Y., Yabuki, Y., Doi, M., Sato, Y., Tanaka, M. & Kurikara, M. (2012). J. Pept. Sci. 18, 466-475.
Flack, H. D. & Bernardinelli, G. (1999). Acta Cryst. A55, 908-915.
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