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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 66| Part 11| November 2010| Pages o2750-o2751
https://doi.org/10.1107/S1600536810039589

(3R,4R,5R)-5-(Acetamido­meth­yl)-N-benzyl-3,4-dihy­dr­oxy­tetra­hydro­furan-3-carboxamide

Michela I. Simone,a* Alison A. Edwards,a‡ Andrew R. Cowley,a George W. J. Fleeta and David J. Watkina

aChemistry Research Laboratory, University of, Oxford, Mansfield Road, Oxford, OX1 3TA, England
*Correspondence e-mail: michela.simone@chem.ox.ac.uk

(Received 17 September 2010; accepted 4 October 2010; online 9 October 2010)

X-ray crystallographic analysis with Cu Kα radiation established the relative configurations of the stereogenic centers in the title compound, C15H20N2O5, and clarified mechanistic ambiguities in the synthesis. The conformation of the five-membered ring approximates twisted, about a C—O bond. The absolute configuration of this carbon-branched dipeptide isostere was known based on the use of D-ribose as the starting material. Refinement of the Flack parameter gave an ambiguous result but the refined Hooft parameter is in agreement with the assumed (D-ribose) absolute structure. The crystal structure consists of N—H⋯O and O—H⋯O hydrogen-bonded bi-layers, with the terminal methyl and phenyl groups forming a hydro­phobic inter-layer inter­face. Some weak C—H⋯O inter­actions are also present.

Related literature

For reviews of sugar amino acids, see: Risseeuw et al. (2007[Risseeuw, M. D. P., Overhand, M., Fleet, G. W. J. & Simone, M. I. (2007). Tetrahedron Asymmetry, 18, 2001-2010.]); Smith & Fleet (1999[Smith, M. D. & Fleet, G. W. J. (1999). J. Pept. Sci. 5, 425-441.]). For investigations of peptidomimetics, see: Smith et al. (1998[Smith, M. D., Claridge, T. D. W., Tranter, G. E., Sansom, M. S. P. & Fleet, G. W. J. (1998). J. Chem. Soc. Chem. Commun. pp. 2041-2042.]); Long et al. (1998[Long, D. D., Smith, M. D., Marquess, D. G., Claridge, T. D. W. & Fleet, G. W. J. (1998). Tetrahedron Lett. 39, 9293-9296.], 1999[Long, D. D., Hungerford, N. L., Smith, M. D., Brittain, D. E. A., Marquess, D. G., Claridge, T. D. W. & Fleet, G. W. J. (1999). Tetrahedron Lett. 40, 2195-2198.]); Claridge et al. (1999[Claridge, T. D. W., Long, D. D., Hungerford, N. L., Smith, M. D., Aplin, R. T., Marquess, D. G. & Fleet, G. W. J. (1999). Tetrahedron Lett. 40, 2199-2203.]); Brittain et al. (2000[Brittain, D. E. A., Watterson, M. P., Claridge, T. D. W., Smith, M. D. & Fleet, G. W. J. (2000). J. Chem. Soc. Perkin Trans. 1, pp. 3655-3665.]); Hungerford et al. (2000[Hungerford, N. L., Claridge, T. D. W., Watterson, M. P., Aplin, R. T., Moreno, A. & Fleet, G. W. J. (2000). J. Chem. Soc. Perkin Trans. 1, pp. 3666-3679.]); Raunkjr et al. (2004[Raunkjr, M., El Oualid, F., van der Marel, G. A., Overkleeft, H. S. & Overhand, M. (2004). Org. Lett. 6, 3167-3170.]); Jockusch et al. (2006[Jockusch, R. A., Talbot, F. O., Rogers, P. S., Simone, M. I., Fleet, G. W. J. & Simons, J. P. (2006). J. Am. Chem. Soc. 128, 16771-16777.]); Tuin et al. (2009[Tuin, A. W., Grotenbreg, G. M., Spalburg, E., de Neeling, A. J., Mars-Groenendijk, R. H., van der Marel, G. A., Noort, D., Overkleeft, H. S. & Overhand, M. (2009). Bioorg. Med. Chem. 17, 6233-6240.]). For crossed-aldol reactions of carbohydrates with formaldehyde, see: Ho (1985[Ho, P. T. (1985). Can. J. Chem. 63, 2221-2224.]); Simone et al. (2005[Simone, M. I., Soengas, R., Newton, C. R., Watkin, D. J. & Fleet, G. W. J. (2005). Tetrahedron Lett. 46, 5761-5765.], 2008[Simone, M. I., Edwards, A. A., Tranter, G. E. & Fleet, G. W. J. (2008). Tetrahedron Asymmetry, 19, 2887-2894.]); Best et al. (2010[Best, D., Jenkinson, S. F., Saville, A. W., Alonzi, D. S., Wormald, M. R., Butters, T. D., Norez, C., Becq, F., Bleriot, Y., Adachi, I., Kato, A. & Fleet, G. W. J. (2010). Tetrahedron Lett. 51, 4170-4174.]). For more strategies for the synthesis of branched carbohydrates, see: Hotchkiss et al. (2004[Hotchkiss, D., Soengas, R., Simone, M. I., van Ameijde, J., Hunter, S., Cowley, A. R. & Fleet, G. W. J. (2004). Tetrahedron Lett. 45, 9461-9464.]); Soengas et al. (2005[Soengas, R., Izumori, K., Simone, M. I., Watkin, D. J., Skytte, U. P., Soetaert, W. & Fleet, G. W. J. (2005). Tetrahedron Lett. 46, 5755-5759.]); Booth et al. (2008[Booth, K. V., da Cruz, F. P., Hotchkiss, D. J., Jenkinson, S. F., Jones, N. A., Weymouth-Wilson, A. C., Clarkson, R., Heinz, T. & Fleet, G. W. J. (2008). Tetrahedron Asymmetry, 19, 2417-2424.]). For a related structure, see: Punzo et al. (2005[Punzo, F., Watkin, D. J., Simone, M. I. & Fleet, G. W. J. (2005). Acta Cryst. E61, o513-o515.]). For the treatment of hydrogen atoms in CRYSTALS, see: Cooper et al. (2010[Cooper, R. I., Thompson, A. L. & Watkin, D. J. (2010). J. Appl. Cryst. 43, 1100-1107.]). For the determination of absolute configuration, see: Hooft et al. (2008[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96-103.]).

[Scheme 1]

Experimental

Crystal data

  • C15H20N2O5

  • Mr = 308.33

  • Orthorhombic, P 21 21 21

  • a = 5.4130 (2) Å

  • b = 8.5082 (2) Å

  • c = 32.6501 (4) Å

  • V = 1503.70 (7) Å3

  • Z = 4

  • Cu Kα radiation

  • μ = 0.86 mm−1

  • T = 150 K

  • 0.35 × 0.20 × 0.04 mm
Data collection

  • Oxford Diffraction Gemini diffractometer

  • Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2002[Oxford Diffraction (2002). CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]) Tmin = 0.95, Tmax = 0.97

  • 12797 measured reflections

  • 1805 independent reflections

  • 1371 reflections with I > 2.0σ(I)

  • Rint = 0.038

  • θmax = 54.3°
Refinement

  • R[F2 > 2σ(F2)] = 0.033

  • wR(F2) = 0.061

  • S = 0.99

  • 1796 reflections

  • 200 parameters

  • H-atom parameters constrained

  • Δρmax = 0.21 e Å−3

  • Δρmin = −0.28 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 681 Friedel pairs

  • Flack parameter: 0.0 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O6—H61⋯O7i 0.80 1.95 2.737 (4) 167
O7—H71⋯O1ii 0.80 2.08 2.821 (4) 154
N10—H101⋯O21i 0.84 2.29 3.023 (4) 147
N19—H191⋯O9iii 0.88 2.04 2.861 (4) 155
C2—H22⋯O21iii 0.98 2.45 3.322 (4) 148
C4—H41⋯O1iv 0.99 2.59 3.520 (4) 156
C4—H41⋯O7i 0.99 2.49 3.257 (4) 134
Symmetry codes: (i) [-x, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iv) x-1, y, z.

Data collection: Gemini (Oxford Diffraction, 2006[Oxford Diffraction (2006). Gemini User Manual. Oxford Diffraction Ltd, Abingdon, England.]); cell refinement: CrysAlis RED (Oxford Diffraction, 2002[Oxford Diffraction (2002). CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]); data reduction: CrysAlis RED; program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.]); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003[Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.]); molecular graphics: CAMERON (Watkin et al., 1996[Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, UK.]); software used to prepare material for publication: CRYSTALS.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810039589/hb5639sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810039589/hb5639Isup2.hkl

checkCIF report


Comment top

δ-Tetrahydrofuran sugar amino acids (THF SAAs) (Risseeuw et al., 2007; Smith and Fleet, 1999) have been extensively used as dipeptide isosteres (Long et al., 1998; Brittain et al., 2000) and incorporated into peptidomimetics (Smith et al., 1998; Hungerford et al., 2000; Raunkjr et al., 2004). The secondary structural preferences induced by THF SAAs upon their incorporation into peptidomimetics have been investigated in a wide variety of systems (Long et al., 1999; Tuin et al., 2009). All these studies have been reported on linear carbon chains, however a number of approaches to branched carbohydrates have been developed (Soengas et al., 2005; Hotchkiss et al., 2004; Booth et al., 2008). This will allow the synthesis of THF SAAs with a branched carbon chain and allow a new family of foldamers to be created.

Compound (4) is a dipeptide isostere bearing a branching carbon substituent at position C-3 of the THF scaffold. The branched peptidomimetic (4) was synthesized in a number of steps from the suitably protected D-ribose derivative (1). A crossed aldol reaction of (1) with formaldehyde (Ho, 1985) gave the resulting lactol which was then further modified to give the carbon-branched lactone trifluoromethanesulfonate (2). Reaction of (2) in acidic methanol (Simone et al., 2008) afforded the branched δ-THF SAA (3). The dipeptide isostere (4) was synthesized from SAA scaffold (3) in four synthetic steps. The crystal structure of an isomeric branched peptidomimetic has been published previously (Punzo et al., 2005). The crystal structure of (4) removes mechanistic ambiguities arising from the Ho crossed aldol condensation and successive modifications of the THF scaffold. Furthermore the crystal structure may provide information about the conformational preference of the scaffold (4) and its corresponding ability to induce any secondary structural features when incorporated into peptidomimetics. The use of D-ribose as the starting material enabled the determination of the absolute configuration of this carbon-branched dipeptide isostere (4).

Related literature top

For reviews of sugar amino acids, see: Risseeuw et al. (2007); Smith & Fleet (1999). For investigations of peptidomimetics, see: Smith et al. (1998); Long et al. (1998, 1999); Claridge et al. (1999); Brittain et al. (2000); Hungerford et al. (2000); Raunkjr et al. (2004); Jockusch et al. (2006); Tuin et al. (2009). For crossed-aldol reactions of carbohydrates with formaldehyde, see: Ho (1985); Simone et al. (2005, 2008); Best et al. (2010). For more strategies for the synthesis of branched carbohydrates, see: Hotchkiss et al. (2004); Soengas et al. (2005); Booth et al. (2008). For a related structure, see: Punzo et al. (2005). For the treatment of hydrogen atoms in CRYSTALS, see: Cooper et al. (2010). For the determination of absolute configuration, see: Hooft et al. (2008).

Experimental top

Compound (4) was dissolved in methanol, ethyl acetate and cyclohexane and then crystallized as the solvent (methanol) evaporated slowly to give crystals of (I) as very thin fragile colourless plates, which readily delaminated on handling. M.p. 428.2–429.2 K; [α]D23 +0.64 (c, 0.70 in methanol) (Simone et al., 2005).

Refinement top

Refinement of the Flack (1983) parameter was inconclusive, 0.0 (3), but the Hooft parameter, 0.01 (6) was in agreement with the known absolute configuration (Hooft et al., 2008).

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, N—H = 0.86, O—H = 0.82 Å) and Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom), after which the positions were refined with riding constraints (Cooper et al., 2010).

Structure description top

δ-Tetrahydrofuran sugar amino acids (THF SAAs) (Risseeuw et al., 2007; Smith and Fleet, 1999) have been extensively used as dipeptide isosteres (Long et al., 1998; Brittain et al., 2000) and incorporated into peptidomimetics (Smith et al., 1998; Hungerford et al., 2000; Raunkjr et al., 2004). The secondary structural preferences induced by THF SAAs upon their incorporation into peptidomimetics have been investigated in a wide variety of systems (Long et al., 1999; Tuin et al., 2009). All these studies have been reported on linear carbon chains, however a number of approaches to branched carbohydrates have been developed (Soengas et al., 2005; Hotchkiss et al., 2004; Booth et al., 2008). This will allow the synthesis of THF SAAs with a branched carbon chain and allow a new family of foldamers to be created.

Compound (4) is a dipeptide isostere bearing a branching carbon substituent at position C-3 of the THF scaffold. The branched peptidomimetic (4) was synthesized in a number of steps from the suitably protected D-ribose derivative (1). A crossed aldol reaction of (1) with formaldehyde (Ho, 1985) gave the resulting lactol which was then further modified to give the carbon-branched lactone trifluoromethanesulfonate (2). Reaction of (2) in acidic methanol (Simone et al., 2008) afforded the branched δ-THF SAA (3). The dipeptide isostere (4) was synthesized from SAA scaffold (3) in four synthetic steps. The crystal structure of an isomeric branched peptidomimetic has been published previously (Punzo et al., 2005). The crystal structure of (4) removes mechanistic ambiguities arising from the Ho crossed aldol condensation and successive modifications of the THF scaffold. Furthermore the crystal structure may provide information about the conformational preference of the scaffold (4) and its corresponding ability to induce any secondary structural features when incorporated into peptidomimetics. The use of D-ribose as the starting material enabled the determination of the absolute configuration of this carbon-branched dipeptide isostere (4).

For reviews of sugar amino acids, see: Risseeuw et al. (2007); Smith & Fleet (1999). For investigations of peptidomimetics, see: Smith et al. (1998); Long et al. (1998, 1999); Claridge et al. (1999); Brittain et al. (2000); Hungerford et al. (2000); Raunkjr et al. (2004); Jockusch et al. (2006); Tuin et al. (2009). For crossed-aldol reactions of carbohydrates with formaldehyde, see: Ho (1985); Simone et al. (2005, 2008); Best et al. (2010). For more strategies for the synthesis of branched carbohydrates, see: Hotchkiss et al. (2004); Soengas et al. (2005); Booth et al. (2008). For a related structure, see: Punzo et al. (2005). For the treatment of hydrogen atoms in CRYSTALS, see: Cooper et al. (2010). For the determination of absolute configuration, see: Hooft et al. (2008).

Computing details top

Data collection: Gemini (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2002); data reduction: CrysAlis RED (Oxford Diffraction, 2002); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS (Betteridge et al., 2003).

Figures top
[Figure 1] Fig. 1. The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
[Figure 2] Fig. 2. The hydrogen bonded bi-layer viewed along the 'a' axis. The hydrophobic faces to the layers explains why the thin platey crystals were extremely fragile.
[Figure 3] Fig. 3. Preparation of the title compound.
(3R,4R,5R)-5-(Acetamidomethyl)-N-benzyl-3,4-dihydroxytetrahydrofuran-3-carboxamide top
Crystal data top
C15H20N2O5Dx = 1.362 Mg m−3
Mr = 308.33Cu Kα radiation, λ = 1.54180 Å
Orthorhombic, P212121Cell parameters from 6490 reflections
a = 5.4130 (2) Åθ = 2–50°
b = 8.5082 (2) ŵ = 0.86 mm−1
c = 32.6501 (4) ÅT = 150 K
V = 1503.70 (7) Å3Plate, colourless
Z = 40.35 × 0.20 × 0.04 mm
F(000) = 656
Data collection top
Oxford Diffraction Gemini
diffractometer		1371 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.038
ω scansθmax = 54.3°, θmin = 5.4°
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2002)		h = −5→5
Tmin = 0.95, Tmax = 0.97k = −8→8
12797 measured reflectionsl = −33→34
1805 independent reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.033 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.1P)2 + 0.0P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.061(Δ/σ)max = 0.0002818
S = 0.99Δρmax = 0.21 e Å−3
1796 reflectionsΔρmin = −0.28 e Å−3
200 parametersAbsolute structure: Flack (1983), 681 Friedel pairs
0 restraintsAbsolute structure parameter: 0.0 (3)
Primary atom site location: structure-invariant direct methods
Crystal data top
C15H20N2O5V = 1503.70 (7) Å3
Mr = 308.33Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 5.4130 (2) ŵ = 0.86 mm−1
b = 8.5082 (2) ÅT = 150 K
c = 32.6501 (4) Å0.35 × 0.20 × 0.04 mm
Data collection top
Oxford Diffraction Gemini
diffractometer		1805 independent reflections
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2002)		1371 reflections with I > 2.0σ(I)
Tmin = 0.95, Tmax = 0.97Rint = 0.038
12797 measured reflectionsθmax = 54.3°
Refinement top
R[F2 > 2σ(F2)] = 0.033H-atom parameters constrained
wR(F2) = 0.061Δρmax = 0.21 e Å−3
S = 0.99Δρmin = −0.28 e Å−3
1796 reflectionsAbsolute structure: Flack (1983), 681 Friedel pairs
200 parametersAbsolute structure parameter: 0.0 (3)
0 restraints
Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1 K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105 107.

The 9 missing reflections are all low-angle and in the penumbra of the beam trap. Their indices are 1 0 1 0 1 1 0 1 2 0 1 3 0 0 4 0 1 4 0 1 5 0 0 6

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.5384 (3)0.54901 (19)0.24407 (4)0.0310
C20.5370 (4)0.5114 (3)0.28721 (7)0.0285
C30.2641 (4)0.5070 (3)0.29786 (7)0.0260
C40.1541 (4)0.4286 (3)0.25891 (7)0.0254
C50.3580 (4)0.4433 (3)0.22659 (7)0.0292
O60.1751 (3)0.6640 (2)0.30274 (4)0.0326
O70.0770 (3)0.27045 (18)0.26442 (4)0.0315
C80.2035 (5)0.4123 (4)0.33591 (8)0.0282
O90.3097 (3)0.2865 (2)0.34244 (5)0.0385
N100.0228 (4)0.4687 (2)0.35927 (6)0.0333
C11−0.0761 (5)0.3862 (3)0.39501 (7)0.0386
C120.0572 (5)0.4266 (4)0.43394 (8)0.0357
C130.2683 (6)0.3472 (4)0.44544 (9)0.0475
C140.3884 (6)0.3856 (4)0.48131 (11)0.0609
C150.3030 (7)0.5041 (5)0.50564 (9)0.0650
C160.0949 (7)0.5856 (4)0.49430 (9)0.0609
C17−0.0278 (5)0.5475 (4)0.45838 (8)0.0465
C180.2707 (4)0.5031 (3)0.18519 (7)0.0335
N190.4531 (4)0.4865 (2)0.15327 (6)0.0334
C200.4739 (5)0.3543 (4)0.13069 (8)0.0327
O210.3280 (4)0.2440 (2)0.13419 (5)0.0418
C220.6860 (5)0.3518 (3)0.10127 (8)0.0482
H610.12230.69450.28140.0479*
H710.19690.21860.26940.0465*
H101−0.03170.55820.35380.0384*
H1910.55860.56380.14970.0387*
H220.63020.59040.30290.0333*
H210.61240.40780.29130.0332*
H410.00660.48760.24990.0266*
H510.43040.33720.22250.0326*
H111−0.24740.41420.39830.0447*
H112−0.06310.27060.38880.0441*
H1310.33260.26590.42870.0566*
H1410.53000.32720.48830.0728*
H1510.38640.52820.53070.0784*
H1610.02780.66520.51110.0716*
H171−0.16950.60310.45050.0557*
H1810.22600.61670.18690.0395*
H1820.12390.44460.17780.0396*
H2230.67190.26780.08200.0701*
H2220.84020.34750.11500.0711*
H2210.68890.44460.08540.0713*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0310 (9)0.0329 (11)0.0290 (10)−0.0035 (9)−0.0004 (8)0.0013 (9)
C20.0288 (17)0.0261 (19)0.0305 (16)0.0022 (15)−0.0051 (13)0.0002 (13)
C30.0303 (17)0.0240 (19)0.0237 (16)0.0006 (15)0.0003 (12)0.0029 (14)
C40.0291 (14)0.0156 (18)0.0313 (16)0.0013 (13)−0.0048 (14)0.0002 (14)
C50.0299 (15)0.0260 (18)0.0316 (16)−0.0019 (16)0.0001 (13)−0.0043 (15)
O60.0433 (11)0.0236 (13)0.0309 (11)0.0047 (10)−0.0042 (9)−0.0010 (9)
O70.0303 (11)0.0251 (12)0.0390 (10)−0.0027 (9)−0.0010 (8)−0.0005 (9)
C80.0280 (17)0.028 (2)0.0287 (18)−0.0011 (17)−0.0022 (15)−0.0061 (16)
O90.0453 (12)0.0285 (12)0.0417 (12)0.0080 (11)0.0038 (10)0.0052 (10)
N100.0378 (13)0.0288 (15)0.0334 (13)0.0078 (13)−0.0003 (12)0.0038 (11)
C110.0394 (18)0.044 (2)0.0322 (17)−0.0018 (16)0.0059 (15)0.0031 (15)
C120.0366 (18)0.042 (2)0.0282 (17)−0.0039 (18)0.0041 (16)0.0094 (17)
C130.048 (2)0.054 (2)0.041 (2)−0.003 (2)0.0050 (18)0.0083 (18)
C140.046 (2)0.077 (3)0.059 (2)−0.009 (2)−0.008 (2)0.021 (2)
C150.072 (3)0.081 (3)0.042 (2)−0.022 (3)−0.010 (2)0.005 (2)
C160.072 (3)0.066 (3)0.044 (2)−0.007 (2)0.007 (2)−0.0091 (19)
C170.0511 (19)0.050 (2)0.0382 (18)0.0005 (19)0.0049 (18)0.0023 (17)
C180.0340 (16)0.032 (2)0.0346 (17)−0.0018 (15)0.0013 (14)−0.0018 (15)
N190.0367 (13)0.0319 (16)0.0318 (13)−0.0115 (13)0.0074 (12)−0.0025 (12)
C200.0385 (19)0.034 (2)0.0254 (16)0.0013 (19)−0.0072 (17)0.0015 (17)
O210.0472 (13)0.0319 (14)0.0462 (12)−0.0103 (11)0.0017 (11)−0.0039 (10)
C220.052 (2)0.054 (2)0.0389 (18)0.0002 (18)0.0118 (17)−0.0006 (16)
Geometric parameters (Å, º) top
O1—C21.444 (2)C12—C131.379 (3)
O1—C51.445 (3)C12—C171.381 (4)
C2—C31.518 (3)C13—C141.379 (4)
C2—H220.983C13—H1310.948
C2—H210.981C14—C151.364 (4)
C3—C41.555 (3)C14—H1410.941
C3—O61.429 (3)C15—C161.373 (4)
C3—C81.517 (3)C15—H1510.956
C4—C51.532 (3)C16—C171.386 (3)
C4—O71.420 (2)C16—H1610.945
C4—H410.988C17—H1710.937
C5—C181.520 (3)C18—N191.443 (3)
C5—H510.993C18—H1810.998
O6—H610.796C18—H1820.968
O7—H710.801N19—C201.350 (3)
C8—O91.234 (3)N19—H1910.879
C8—N101.330 (3)C20—O211.232 (3)
N10—C111.463 (3)C20—C221.497 (3)
N10—H1010.836C22—H2230.956
C11—C121.501 (3)C22—H2220.947
C11—H1110.963C22—H2210.945
C11—H1121.007
C2—O1—C5104.10 (17)H111—C11—H112109.4
O1—C2—C3103.53 (17)C11—C12—C13121.1 (3)
O1—C2—H22110.7C11—C12—C17120.0 (3)
C3—C2—H22113.4C13—C12—C17118.9 (3)
O1—C2—H21109.3C12—C13—C14120.4 (3)
C3—C2—H21110.6C12—C13—H131120.3
H22—C2—H21109.2C14—C13—H131119.3
C2—C3—C4101.29 (19)C13—C14—C15120.7 (3)
C2—C3—O6109.3 (2)C13—C14—H141117.6
C4—C3—O6111.3 (2)C15—C14—H141121.7
C2—C3—C8114.3 (2)C14—C15—C16119.6 (3)
C4—C3—C8111.0 (2)C14—C15—H151119.8
O6—C3—C8109.4 (2)C16—C15—H151120.6
C3—C4—C5104.63 (19)C15—C16—C17120.2 (3)
C3—C4—O7114.56 (19)C15—C16—H161121.4
C5—C4—O7112.09 (19)C17—C16—H161118.3
C3—C4—H41109.5C16—C17—C12120.2 (3)
C5—C4—H41109.7C16—C17—H171120.5
O7—C4—H41106.4C12—C17—H171119.3
C4—C5—O1105.40 (17)C5—C18—N19113.39 (19)
C4—C5—C18114.6 (2)C5—C18—H181110.5
O1—C5—C18110.66 (19)N19—C18—H181107.5
C4—C5—H51107.7C5—C18—H182107.8
O1—C5—H51110.6N19—C18—H182109.3
C18—C5—H51107.9H181—C18—H182108.2
C3—O6—H61109.1C18—N19—C20122.2 (2)
C4—O7—H71108.0C18—N19—H191117.8
C3—C8—O9120.1 (2)C20—N19—H191119.9
C3—C8—N10115.9 (3)N19—C20—O21122.1 (2)
O9—C8—N10123.8 (2)N19—C20—C22115.2 (3)
C8—N10—C11123.6 (2)O21—C20—C22122.7 (3)
C8—N10—H101117.8C20—C22—H223111.9
C11—N10—H101118.5C20—C22—H222111.9
N10—C11—C12112.9 (2)H223—C22—H222110.6
N10—C11—H111108.9C20—C22—H221110.7
C12—C11—H111108.1H223—C22—H221105.3
N10—C11—H112106.4H222—C22—H221106.0
C12—C11—H112111.2
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O6—H61···O7i0.801.952.737 (4)167
O7—H71···O1ii0.802.082.821 (4)154
N10—H101···O21i0.842.293.023 (4)147
N19—H191···O9iii0.882.042.861 (4)155
C2—H22···O21iii0.982.453.322 (4)148
C4—H41···O1iv0.992.593.520 (4)156
C4—H41···O7i0.992.493.257 (4)134
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) −x+1, y−1/2, −z+1/2; (iii) −x+1, y+1/2, −z+1/2; (iv) x−1, y, z.

Experimental details

Crystal data
Chemical formulaC15H20N2O5
Mr308.33
Crystal system, space groupOrthorhombic, P212121
Temperature (K)150
a, b, c (Å)5.4130 (2), 8.5082 (2), 32.6501 (4)
V (Å3)1503.70 (7)
Z4
Radiation typeCu Kα
µ (mm−1)0.86
Crystal size (mm)0.35 × 0.20 × 0.04
Data collection
DiffractometerOxford Diffraction Gemini
Absorption correctionMulti-scan
(CrysAlis RED; Oxford Diffraction, 2002)
Tmin, Tmax0.95, 0.97
No. of measured, independent and
observed [I > 2.0σ(I)] reflections		12797, 1805, 1371
Rint0.038
θmax (°)54.3
(sin θ/λ)max (Å−1)0.527
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.033, 0.061, 0.99
No. of reflections1796
No. of parameters200
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.21, −0.28
Absolute structureFlack (1983), 681 Friedel pairs
Absolute structure parameter0.0 (3)

Computer programs: Gemini (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2002), SIR92 (Altomare et al., 1994), CRYSTALS (Betteridge et al., 2003), CAMERON (Watkin et al., 1996).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O6—H61···O7i0.801.952.737 (4)167
O7—H71···O1ii0.802.082.821 (4)154
N10—H101···O21i0.842.293.023 (4)147
N19—H191···O9iii0.882.042.861 (4)155
C2—H22···O21iii0.982.453.322 (4)148
C4—H41···O1iv0.992.593.520 (4)156
C4—H41···O7i0.992.493.257 (4)134
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) −x+1, y−1/2, −z+1/2; (iii) −x+1, y+1/2, −z+1/2; (iv) x−1, y, z.
 

Footnotes

‡Present address: Medway School of Pharmacy, Universities of Kent and Greenwich at Medway, Central Avenue, Chatham Maritime, Kent, ME4 4TB, England.

Acknowledgements

Financial support to MIS provided through the European Community's Human Potential Programme under contract HPRN-CT-2002–00173 is gratefully acknowledged.

References

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ISSN: 2056-9890
Volume 66| Part 11| November 2010| Pages o2750-o2751
https://doi.org/10.1107/S1600536810039589
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