research communications
Multicentered hydrogen bonding in 1-[(1-deoxy-β-D-fructopyranos-1-yl)azaniumyl]cyclopentanecarboxylate (`D-fructose-cycloleucine')
aDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA, bDepartment of Chemistry, University of Missouri, Columbia, MO 65211, USA, and cDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, U.S.A.
*Correspondence e-mail: MossineV@missouri.edu
The title compound, C12H21NO7, (I), is conformationally unstable; the predominant form present in its solution is the β-pyranose form (74.3%), followed by the β- and α-furanoses (12.1 and 10.2%, respectively), α-pyranose (3.4%), and traces of the acyclic carbohydrate tautomer. In the crystalline state, the carbohydrate part of (I) adopts the 2C5 β-pyranose conformation, and the amino acid portion exists as a zwitterion, with the side chain cyclopentane ring assuming the E9 All heteroatoms are involved in hydrogen bonding that forms a system of antiparallel infinite chains of fused R33(6) and R33(8) rings. The molecule features extensive intramolecular hydrogen bonding, which is uniquely multicentered and involves the carboxylate, ammonium and carbohydrate hydroxy groups. In contrast, the contribution of intermolecular O⋯H/H⋯O contacts to the Hirshfeld surface is relatively low (38.4%), as compared to structures of other D-fructose-amino acids. The 1H NMR data suggest a slow rotation around the C1—C2 bond in (I), indicating that the intramolecular heteroatom contacts survive in aqueous solution of the molecule as well.
Keywords: crystal structure; fructosamine; Amadori rearrangement; cycloleucine; hydrogen bonding; Hirshfeld surface analysis.
CCDC reference: 1583255
1. Chemical context
D-Fructosamine derivatives are products of non-enzymatic condensation reactions between D-glucose and biomolecules containing free aliphatic amino groups, such as amino acids, proteins, aminophospholipids, or biogenic (Mossine & Mawhinney, 2010). D-Fructosamines are thus present in all living systems and in foods. For instance, in healthy humans, about 5% of plasma proteins are decorated with fructosamine residues, while dietary intake of D-fructosamines, primarily in the form of N∊-(1-deoxy-D-fructos-1-yl)-L-lysine, has been estimated at 1 g per day. Although the normal physiological functions of D-fructosamines are not understood, a number of bacterial, fungal, and mammalian carbohydrate-processing enzymes (Wu & Monnier, 2003; Van Schaftingen et al., 2012), transporters (Marty et al., 2016), and (Mossine et al., 2008) can recognize D-fructosamine, thus implying the participation of this structure in metabolic and signaling processes. Biomedical research has suggested the involvement of D-fructosamines in the development of diabetic complications (Wu & Monnier, 2003), bacterial infections (Ali et al., 2014), and cancer (Malmström et al., 2016). We and others (Mossine et al., 2010; Rabinovich et al., 2006) have demonstrated the efficacy of synthetic D-fructosamine derivatives as blockers of galectins, a family of tumor-associated In this context, several structure determinations of biologically active fructosamines have previously been undertaken (Mossine et al., 2007a,b, 2009, 2018).
As a part of our search for efficient blockers of galectins-1, −3 and −4, we have prepared D-fructose-cycloleucine (I), a structural analog of the galectin inhibitor D-fructose-L-leucine (Mossine et al., 2008). Here we report on the molecular and crystal structures of (I), with an emphasis on the hydrogen-bonding patterns in the structure.
2. Structural commentary
The molecular structure and atomic numbering are shown in Fig. 1. The title compound, (I), crystallizes in the monoclinic P21, with two equivalent molecules per The molecule may be considered as a conjugate of a carbohydrate, 1-amino-1-deoxy-D-fructose, and an amino acid, 1-aminocyclopentane-1-carboxylic acid, which are joined through the common amino group. The β-D-pyranose ring of the carbohydrate portion exists in the 2C5 or 1C(D) chair conformation, with puckering parameters Q = 0.5763 Å, θ = 172.71°, and φ = 248.80°. These parameters correspond to a conformation with the lowest energy possible for fructose (French et al., 1997). The bond distances and the valence angles are close to the average values for a number of crystalline pyranose structures (Jeffrey & Taylor, 1980). In an aqueous solution of (I), the β-D-pyranose anomer dominates the tautomeric equilibrium (Fig. 2), at 74.3%, as follows from its 13C NMR spectrum (Table 1). The acyclic forms are not readily detectable because of their low populations; their presence is suggested based on literature evidence available for other fructosamine derivatives (Table 1). In the 1H NMR spectrum of the major anomer, the vicinal proton–proton coupling constants J3,4 = 9.8 Hz and J4,5 = 3.4 Hz indicate that atom H4 is in a trans disposition to H3 and in a gauche disposition to H5. Hence, the predominant conformation of D-fructose-cycloleucine in solution is also 2C5 β-D-fructopyranose.
The amino acid portion of the molecule is in the zwitterionic form, with a positively charged tetrahedral secondary ammonium nitrogen atom and a negatively charged deprotonated carboxyl group. The side-chain cyclopentane ring is, by the atom numbering in Fig. 1, in the E9 (envelope on C9) or Cs—Cγ-exo conformation, with puckering parameters Q = 0.4220 Å, φ = 254.94°, and pseudorotational parameters (Rao et al., 1981) P = 56.9° and τ = 43.7° for the C7—C8 bond.
The ammonium group and all but one (O8) oxygen atoms are involved in intramolecular hydrogen bonding (Table 2). At the centre of this system are heteroatom contacts between the conjugated carbohydrate and the amino acid portions of the molecule, which involve the carboxylate atom O7, the ammonium atom H1A, the pyranose ring atom O5, and the anomeric hydroxyl group O1—H1O (Fig. 1). Although the value of N1—H1A⋯O7 angle is 99.4°, the distance N1⋯O7 is 2.702 (2) Å, short enough for this heteroatom contact to qualify as a strong hydrogen bond. Then the central motif of the intramolecular hydrogen-bonded structure can be described in terms of a compact ring S22(4) pattern represented by the four-atom O7⋯H1A⋯O1—H1O⋯O7 cycle. In the 1H NMR spectrum of (I), two protons, H1C and H1D, which are attached to C1, produce two distinct signals at 3.332 and 3.199 ppm, with J1C,1D = −12.8 Hz (Fig. 3). The non-equivalence of these protons indicates around the C1—C2 and C1—N1 bonds, thus suggesting the intramolecular hydrogen bonding retains this structure in solution.
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3. Supramolecular features
The crystal packing of (I) features infinite chains of antiparallel hydrogen bonds running along the a-axis direction (Fig. 4). The basic hydrogen-bonding patterns are depicted in Fig. 5 and include two rings, R33(6) and R33(8), and a small finite chain D22(4). Alternatively, the fused rings pattern can be described in terms of two chains, C22(4) and C33(8). The ammonium proton H1A is involved in a rare five-centered hydrogen bond, involving three weakly directional intramolecular contacts with O1, O5, and O7 (at distances of 2.59, 2.43, and 2.40 Å, respectively) and one intermolecular, shorter (2.00 Å distance) bond with O3. The carboxyl atom O7 is also involved in an unusual multicenter hydrogen bond, by coordinating four surrounding protons at reasonably short distances, 1.97–2.40 Å (Tables 2 and 3). This multicentered character of the short heteroatom contacts implies a significant contribution of the electrostatic component (Tao et al., 2017) to the interaction, apparently between the positively charged ammonium group and the negatively charged carboxyl atom O7 (Fig. 6). Indeed, the C12—O7 bond [1.269 (3) Å] is significantly longer than the C12—O8 distance [1.243 (3) Å], suggesting a more polarized character of the former. This may be a consequence of highly differing heteroatom arrangements around the two carboxylate oxygen atoms in the crystal. One, O7, is surrounded by four heteroatoms (O1, O3, O4, N1) at distances qualifying for hydrogen bonds, while O8 has only one heteroatom, N1, located at a short distance.
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The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) revealed that a major proportion of the intermolecular contacts in of (I) is provided by non- or low-polar H⋯H interactions (Fig. 7). Of note, there are three short interatomic contacts of the C—H⋯O type (Table 3, Fig. 6) that involve the cyclopentane ring and which may be responsible for conformational stabilization of the ring. In contrast, a number of published cycloleucine structures feature disordered conformations as a result of the ring pucker pseudorotation (Mallikarjunan et al., 1972; Varughese & Chacko, 1978; Santini et al. 1988).
4. Database survey
Searches of SciFinder (2018) and the Cambridge Structural Database (2019 CSD release; Groom et al., 2016) by both structure and chemical names returned no previous structural description of N-(1-deoxy-β-D-fructopyranos-1-yl)-1′-aminocyclopentane-1′-carboxylic acid or D-fructose-cycloleucine; thus the compound appears to be novel. Since the conformational instability of the D-fructosamine moiety determines the chemical reactivities and biological activities of D-fructosamine derivatives (Mossine & Mawhinney, 2010), we compared the structure of (I) with solved structures of other D-fructose-amino acids. The most closely related structures are D-fructose-2-aminoisobutyric acid (CCDC 1583254; Mossine et al., 2018), D-fructose-glycine (CCDC 1307697; Mossine, Glinsky et al., 1995), D-fructose-L-proline [CCDC 628806 and 628807 (Tarnawski et al., 2007), 631528 (Mossine et al., 2007a)], and D-fructose-L-histidine (CCDC 622419; Mossine et al., 2007b). Although some fructosamine derivatives can crystallize as the β-furanose, spiro-bicyclic hemiketal, or acyclic keto tautomers (Mossine, Barnes et al., 1995, 2009), all of the above-listed D-fructose-amino acids adopt the 2C5 β-pyranose conformation and exist as with the intramolecular hydrogen-bonding central pattern localized around the ammonium group and involving the carboxylate and one hydroxyl group donated by the carbohydrate moiety. This hydrogen-bonded conjugation between the amino acid zwitterion bridge and the β-pyranose provides for conformational stability around the C1—C2 bond in solutions of D-fructose-amino acids. The staggered gauche–trans conformation of the N1—C1—C2—O5 torsion, such as in (I), has also been observed in CCDC 1583254 (molecule A; Mossine et al., 2018), CCDC 631528 (Mossine et al., 2007a), and CCDC 622419 (Mossine et al., 2007b), while the trans–gauche conformation was observed in four other structures of D-fructose-amino acids (Table 4). However, none of these structures, except (I), features the cyclic motif of intramolecular multicentered hydrogen bonding (Fig. 1), which is supported by a unique direct interaction between the carbohydrate anomeric hydroxyl donor, O1—H1O, and the carboxylate acceptor, O7. In total, there are six intramolecular short heteroatom contacts in the structure of (I), more than in any other D-fructose-amino acid structure known to date. Such effect of the `internalization' of hydrogen bonding in (I) is also revealed in a comparative analysis of the fingerprint plots (Fig. 7) that are based on the calculations of Hirshfeld surfaces (Spackman & Jayatilaka, 2009) and delineated into the O⋯H/H⋯O intermolecular contacts in the of (I). The relative abundance of these contacts in structures of D-fructose-amino acids decreases with an increase in the number of intramolecular hydrogen bonds; this trend is clearly revealed by the data presented in Table 4. The significant difference between the carboxylate C—O lengths of 0.026 Å in (I) is comparable to the respective bond-length differences noted in other fructose-amino acid structures, including CCDC 1583254 (0.022 Å in molecule B; Mossine et al., 2018) and CCDC 622419 (0.021 Å; Mossine et al., 2007b). In the latter two structures, the carboxylate oxygen atoms are involved in close heteroatom contacts unequally, although not to the extent observed in (I).
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5. Synthesis and crystallization
Cycloleucine (2.6 g, 0.02 mol), D-glucose (9 g, 0.05 mol), and sodium acetate (0.82 g, 0.01 mol) were dissolved in 100 mL of a methanol/glycerol (3:1) mixture and refluxed for 3 h. The reaction progress was monitored by TLC on silica. The reaction mixture was diluted with 900 mL of water and passed through a column charged with 80 mL of Amberlite IRN-77 (H+-form). The target compound was then eluted with 0.2 M pyridine, and fractions containing pure (I) were pooled and evaporated. The residue was redissolved in 100 mL of water, decolorized with 0.5 g of and evaporated to a syrup. The latter was dissolved in 30 mL of ethanol and made nearly cloudy with the dropwise addition of acetone. Crystallization occurred within a week at room temperature. Yield 3.4 g (58%, based on the starting cycloleucine).
Major β-pyranose tautomer peaks (ppm) in 13C NMR spectrum in D2O: 179.82 (C12); 98.34 (C2); 76.30 (C7); 72.33 (C4); 72.20 (C3); 71.80 (C5); 66.66 (C6); 52.89 (C1); 37.44, 37.40 (C8, C11); 28.00, 27.98 (C9, C10). See Table 1 for minor peaks assignments in the spectrum. Major signals (ppm) and resolved coupling constants (Hz) in the 1H NMR spectrum: 4.035 (dd, H6B); 4.017 (m, H5); 3.896 (dd, H4); 3.774 (d, H3); 3.771 (dd, H6A); 3.332 (d, H1D); 3.199 (d, H1C); 2.220 (m, 2H11); 1.955 (m, 2H8); 1.83 (m, 2H9 + 2H10); J1C,1D = −12.8; J3,4 = 9.8; J4,5 = 3.4; J5,6A = 1.3; J6A,6B = −12.9.
6. details
Crystal data, data collection and structure . Hydroxyl H atoms were located in difference-Fourier maps and were allowed to refine freely. Other H atoms were placed at calculated positions and treated as riding, with N—H = 0.91 Å, C—H = 0.99 Å (methylene) or 1.00 Å (methine) and with Uiso(H) = 1.2Ueq (methine or methylene). As a result of the unrealistic value obtained for the Flack parameter [−0.4 (4) for 1097 quotients; Parsons et al., 2013], the of the pyranose ring system (2R,3S,4R,5R) was assigned on the basis of the known configuration for the starting compound D-glucose (McNaught, 1996).
details are summarized in Table 5
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Supporting information
CCDC reference: 1583255
https://doi.org/10.1107/S2056989019009253/eb2020sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019009253/eb2020Isup2.hkl
Data collection: SMART (Bruker, 1998); cell
SAINT-Plus (Bruker, 1998); data reduction: SAINT-Plus (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2017/1 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: CIFTAB (Sheldrick, 2008) and publCIF (Westrip, 2010).C12H21NO7 | F(000) = 312 |
Mr = 291.30 | Dx = 1.457 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.8052 (3) Å | Cell parameters from 3178 reflections |
b = 11.9540 (6) Å | θ = 2.7–27.1° |
c = 9.6135 (5) Å | µ = 0.12 mm−1 |
β = 95.506 (1)° | T = 100 K |
V = 664.05 (6) Å3 | Plate, colourless |
Z = 2 | 0.55 × 0.25 × 0.10 mm |
Bruker APEXII CCD area detector diffractometer | 2619 reflections with I > 2σ(I) |
ω scans | Rint = 0.017 |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | θmax = 27.1°, θmin = 2.1° |
Tmin = 0.72, Tmax = 0.99 | h = −7→7 |
4797 measured reflections | k = −15→15 |
2761 independent reflections | l = −12→10 |
Refinement on F2 | Hydrogen site location: mixed |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.029 | w = 1/[σ2(Fo2) + (0.0364P)2 + 0.1566P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.073 | (Δ/σ)max = 0.001 |
S = 1.03 | Δρmax = 0.23 e Å−3 |
2761 reflections | Δρmin = −0.20 e Å−3 |
197 parameters | Absolute structure: Flack x determined using 1097 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013). |
1 restraint | Absolute structure parameter: −0.4 (4) |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.7009 (3) | 0.99423 (13) | 0.44759 (17) | 0.0210 (3) | |
O2 | 0.6482 (3) | 1.23008 (14) | 0.42123 (17) | 0.0236 (4) | |
O3 | 0.9451 (3) | 1.26855 (13) | 0.68102 (17) | 0.0223 (3) | |
O4 | 1.3447 (3) | 1.16847 (15) | 0.61241 (19) | 0.0271 (4) | |
O5 | 1.0920 (3) | 1.01394 (12) | 0.41337 (15) | 0.0200 (3) | |
O7 | 0.4680 (3) | 0.86115 (14) | 0.24446 (16) | 0.0215 (3) | |
O8 | 0.2727 (3) | 0.93833 (15) | 0.05537 (16) | 0.0283 (4) | |
N1 | 0.8644 (3) | 0.95057 (15) | 0.16816 (17) | 0.0160 (3) | |
H1A | 0.872660 | 0.899266 | 0.238389 | 0.019* | |
H1B | 1.003891 | 0.951327 | 0.132317 | 0.019* | |
C1 | 0.8227 (4) | 1.06402 (17) | 0.2287 (2) | 0.0189 (4) | |
H1C | 0.661121 | 1.087516 | 0.201456 | 0.023* | |
H1D | 0.927252 | 1.119552 | 0.191299 | 0.023* | |
C2 | 0.8665 (4) | 1.05974 (17) | 0.3875 (2) | 0.0182 (4) | |
C3 | 0.8630 (4) | 1.17629 (17) | 0.4547 (2) | 0.0177 (4) | |
H3 | 0.986207 | 1.222671 | 0.417043 | 0.021* | |
C4 | 0.9241 (4) | 1.16278 (17) | 0.6125 (2) | 0.0178 (4) | |
H4 | 0.799149 | 1.118808 | 0.652062 | 0.021* | |
C5 | 1.1540 (4) | 1.10136 (18) | 0.6441 (2) | 0.0205 (4) | |
H5 | 1.173771 | 1.081867 | 0.745658 | 0.025* | |
C6 | 1.1571 (4) | 0.99419 (18) | 0.5592 (2) | 0.0215 (5) | |
H6A | 1.314355 | 0.961418 | 0.570981 | 0.026* | |
H6B | 1.048878 | 0.939529 | 0.594849 | 0.026* | |
C7 | 0.6822 (3) | 0.91363 (17) | 0.0555 (2) | 0.0164 (4) | |
C8 | 0.6746 (4) | 0.99140 (19) | −0.0720 (2) | 0.0202 (4) | |
H8A | 0.549752 | 1.047572 | −0.069571 | 0.024* | |
H8B | 0.824036 | 1.030727 | −0.075537 | 0.024* | |
C9 | 0.6270 (4) | 0.9129 (2) | −0.1969 (2) | 0.0270 (5) | |
H9A | 0.461610 | 0.891584 | −0.210590 | 0.032* | |
H9B | 0.672248 | 0.947623 | −0.283720 | 0.032* | |
C10 | 0.7793 (5) | 0.8121 (2) | −0.1546 (2) | 0.0295 (5) | |
H10A | 0.943566 | 0.827661 | −0.167132 | 0.035* | |
H10B | 0.728704 | 0.745231 | −0.210171 | 0.035* | |
C11 | 0.7450 (4) | 0.79532 (18) | 0.0003 (2) | 0.0220 (4) | |
H11A | 0.888615 | 0.766805 | 0.052214 | 0.026* | |
H11B | 0.618351 | 0.741477 | 0.011014 | 0.026* | |
C12 | 0.4522 (4) | 0.90500 (18) | 0.1238 (2) | 0.0188 (4) | |
H4O | 1.347 (5) | 1.227 (3) | 0.662 (3) | 0.032 (8)* | |
H1O | 0.631 (6) | 0.955 (3) | 0.390 (4) | 0.042 (9)* | |
H3O | 0.814 (6) | 1.296 (3) | 0.684 (3) | 0.037 (8)* | |
H2O | 0.553 (6) | 1.199 (3) | 0.463 (3) | 0.037 (9)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0221 (8) | 0.0233 (8) | 0.0179 (7) | −0.0065 (6) | 0.0033 (6) | −0.0029 (6) |
O2 | 0.0212 (9) | 0.0230 (8) | 0.0263 (9) | 0.0047 (7) | 0.0009 (7) | 0.0015 (7) |
O3 | 0.0165 (8) | 0.0229 (7) | 0.0272 (9) | 0.0015 (6) | 0.0009 (6) | −0.0097 (6) |
O4 | 0.0173 (8) | 0.0290 (9) | 0.0359 (9) | −0.0021 (7) | 0.0066 (7) | −0.0129 (8) |
O5 | 0.0191 (8) | 0.0227 (8) | 0.0180 (7) | 0.0022 (6) | 0.0014 (6) | −0.0033 (6) |
O7 | 0.0184 (7) | 0.0269 (8) | 0.0195 (8) | −0.0031 (6) | 0.0037 (6) | 0.0034 (6) |
O8 | 0.0144 (7) | 0.0461 (11) | 0.0244 (8) | 0.0031 (7) | 0.0019 (6) | 0.0037 (8) |
N1 | 0.0130 (8) | 0.0193 (8) | 0.0159 (8) | −0.0007 (7) | 0.0021 (6) | 0.0008 (7) |
C1 | 0.0215 (10) | 0.0173 (10) | 0.0180 (10) | −0.0001 (8) | 0.0023 (8) | −0.0006 (8) |
C2 | 0.0182 (10) | 0.0194 (10) | 0.0168 (10) | −0.0008 (8) | 0.0012 (8) | −0.0004 (8) |
C3 | 0.0164 (10) | 0.0177 (10) | 0.0193 (10) | 0.0006 (8) | 0.0026 (8) | −0.0014 (8) |
C4 | 0.0172 (10) | 0.0176 (9) | 0.0187 (10) | −0.0011 (8) | 0.0020 (8) | −0.0033 (8) |
C5 | 0.0182 (10) | 0.0244 (11) | 0.0188 (10) | 0.0011 (9) | 0.0017 (8) | −0.0032 (9) |
C6 | 0.0219 (11) | 0.0214 (10) | 0.0204 (11) | 0.0048 (9) | −0.0018 (8) | −0.0010 (9) |
C7 | 0.0144 (9) | 0.0193 (9) | 0.0155 (9) | −0.0002 (8) | 0.0013 (7) | −0.0009 (8) |
C8 | 0.0202 (11) | 0.0227 (10) | 0.0177 (10) | −0.0020 (8) | 0.0017 (8) | 0.0029 (8) |
C9 | 0.0289 (12) | 0.0334 (12) | 0.0183 (10) | −0.0022 (10) | 0.0005 (9) | 0.0013 (9) |
C10 | 0.0311 (13) | 0.0353 (13) | 0.0226 (12) | 0.0036 (11) | 0.0049 (9) | −0.0055 (10) |
C11 | 0.0239 (11) | 0.0202 (10) | 0.0216 (10) | 0.0019 (8) | 0.0009 (8) | −0.0029 (8) |
C12 | 0.0162 (10) | 0.0205 (9) | 0.0200 (10) | −0.0024 (8) | 0.0038 (8) | −0.0028 (8) |
O1—C2 | 1.406 (3) | C3—H3 | 1.0000 |
O1—H1O | 0.80 (4) | C4—C5 | 1.528 (3) |
O2—C3 | 1.412 (3) | C4—H4 | 1.0000 |
O2—H2O | 0.81 (3) | C5—C6 | 1.520 (3) |
O3—C4 | 1.425 (2) | C5—H5 | 1.0000 |
O3—H3O | 0.84 (4) | C6—H6A | 0.9900 |
O4—C5 | 1.423 (3) | C6—H6B | 0.9900 |
O4—H4O | 0.85 (3) | C7—C8 | 1.535 (3) |
O5—C2 | 1.419 (3) | C7—C12 | 1.547 (3) |
O5—C6 | 1.436 (3) | C7—C11 | 1.566 (3) |
O7—C12 | 1.269 (3) | C8—C9 | 1.529 (3) |
O8—C12 | 1.243 (3) | C8—H8A | 0.9900 |
N1—C1 | 1.504 (3) | C8—H8B | 0.9900 |
N1—C7 | 1.506 (3) | C9—C10 | 1.526 (3) |
N1—H1A | 0.9100 | C9—H9A | 0.9900 |
N1—H1B | 0.9100 | C9—H9B | 0.9900 |
C1—C2 | 1.524 (3) | C10—C11 | 1.535 (3) |
C1—H1C | 0.9900 | C10—H10A | 0.9900 |
C1—H1D | 0.9900 | C10—H10B | 0.9900 |
C2—C3 | 1.537 (3) | C11—H11A | 0.9900 |
C3—C4 | 1.533 (3) | C11—H11B | 0.9900 |
C2—O1—H1O | 111 (2) | C4—C5—H5 | 108.8 |
C3—O2—H2O | 108 (2) | O5—C6—C5 | 111.70 (17) |
C4—O3—H3O | 109 (2) | O5—C6—H6A | 109.3 |
C5—O4—H4O | 108 (2) | C5—C6—H6A | 109.3 |
C2—O5—C6 | 112.75 (15) | O5—C6—H6B | 109.3 |
C1—N1—C7 | 114.50 (16) | C5—C6—H6B | 109.3 |
C1—N1—H1A | 108.6 | H6A—C6—H6B | 107.9 |
C7—N1—H1A | 108.6 | N1—C7—C8 | 111.15 (16) |
C1—N1—H1B | 108.6 | N1—C7—C12 | 106.82 (16) |
C7—N1—H1B | 108.6 | C8—C7—C12 | 114.79 (17) |
H1A—N1—H1B | 107.6 | N1—C7—C11 | 109.76 (17) |
N1—C1—C2 | 109.85 (16) | C8—C7—C11 | 105.47 (17) |
N1—C1—H1C | 109.7 | C12—C7—C11 | 108.79 (17) |
C2—C1—H1C | 109.7 | C9—C8—C7 | 104.14 (18) |
N1—C1—H1D | 109.7 | C9—C8—H8A | 110.9 |
C2—C1—H1D | 109.7 | C7—C8—H8A | 110.9 |
H1C—C1—H1D | 108.2 | C9—C8—H8B | 110.9 |
O1—C2—O5 | 111.62 (17) | C7—C8—H8B | 110.9 |
O1—C2—C1 | 112.06 (17) | H8A—C8—H8B | 108.9 |
O5—C2—C1 | 104.54 (16) | C10—C9—C8 | 102.65 (19) |
O1—C2—C3 | 107.14 (17) | C10—C9—H9A | 111.2 |
O5—C2—C3 | 108.97 (17) | C8—C9—H9A | 111.2 |
C1—C2—C3 | 112.54 (17) | C10—C9—H9B | 111.2 |
O2—C3—C4 | 112.90 (17) | C8—C9—H9B | 111.2 |
O2—C3—C2 | 111.32 (18) | H9A—C9—H9B | 109.1 |
C4—C3—C2 | 108.05 (16) | C9—C10—C11 | 103.64 (19) |
O2—C3—H3 | 108.1 | C9—C10—H10A | 111.0 |
C4—C3—H3 | 108.1 | C11—C10—H10A | 111.0 |
C2—C3—H3 | 108.1 | C9—C10—H10B | 111.0 |
O3—C4—C5 | 107.48 (17) | C11—C10—H10B | 111.0 |
O3—C4—C3 | 111.41 (17) | H10A—C10—H10B | 109.0 |
C5—C4—C3 | 111.20 (17) | C10—C11—C7 | 105.47 (18) |
O3—C4—H4 | 108.9 | C10—C11—H11A | 110.6 |
C5—C4—H4 | 108.9 | C7—C11—H11A | 110.6 |
C3—C4—H4 | 108.9 | C10—C11—H11B | 110.6 |
O4—C5—C6 | 108.13 (17) | C7—C11—H11B | 110.6 |
O4—C5—C4 | 111.66 (18) | H11A—C11—H11B | 108.8 |
C6—C5—C4 | 110.70 (17) | O8—C12—O7 | 126.9 (2) |
O4—C5—H5 | 108.8 | O8—C12—C7 | 117.89 (19) |
C6—C5—H5 | 108.8 | O7—C12—C7 | 115.22 (18) |
C7—N1—C1—C2 | 135.27 (18) | C2—O5—C6—C5 | −59.7 (2) |
C6—O5—C2—O1 | −53.6 (2) | O4—C5—C6—O5 | −71.6 (2) |
C6—O5—C2—C1 | −174.91 (17) | C4—C5—C6—O5 | 51.0 (2) |
C6—O5—C2—C3 | 64.6 (2) | C1—N1—C7—C8 | 63.4 (2) |
N1—C1—C2—O1 | −67.8 (2) | C1—N1—C7—C12 | −62.6 (2) |
N1—C1—C2—O5 | 53.2 (2) | C1—N1—C7—C11 | 179.67 (16) |
N1—C1—C2—C3 | 171.33 (17) | N1—C7—C8—C9 | 142.64 (17) |
O1—C2—C3—O2 | −64.5 (2) | C12—C7—C8—C9 | −96.0 (2) |
O5—C2—C3—O2 | 174.57 (17) | C11—C7—C8—C9 | 23.7 (2) |
C1—C2—C3—O2 | 59.1 (2) | C7—C8—C9—C10 | −40.9 (2) |
O1—C2—C3—C4 | 60.0 (2) | C8—C9—C10—C11 | 42.1 (2) |
O5—C2—C3—C4 | −60.9 (2) | C9—C10—C11—C7 | −27.1 (2) |
C1—C2—C3—C4 | −176.39 (17) | N1—C7—C11—C10 | −117.74 (19) |
O2—C3—C4—O3 | −61.7 (2) | C8—C7—C11—C10 | 2.1 (2) |
C2—C3—C4—O3 | 174.70 (18) | C12—C7—C11—C10 | 125.71 (19) |
O2—C3—C4—C5 | 178.39 (18) | N1—C7—C12—O8 | 139.8 (2) |
C2—C3—C4—C5 | 54.8 (2) | C8—C7—C12—O8 | 16.1 (3) |
O3—C4—C5—O4 | −52.0 (2) | C11—C7—C12—O8 | −101.8 (2) |
C3—C4—C5—O4 | 70.2 (2) | N1—C7—C12—O7 | −41.9 (2) |
O3—C4—C5—C6 | −172.52 (17) | C8—C7—C12—O7 | −165.61 (19) |
C3—C4—C5—C6 | −50.3 (2) | C11—C7—C12—O7 | 76.5 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1B···O8i | 0.91 | 1.80 | 2.704 (2) | 174 |
N1—H1A···O3ii | 0.91 | 2.00 | 2.784 (2) | 143 |
N1—H1A···O1 | 0.91 | 2.59 | 2.980 (2) | 107 |
O4—H4O···O3 | 0.85 (3) | 2.41 (3) | 2.746 (2) | 105 (2) |
O4—H4O···O7iii | 0.85 (3) | 2.09 (3) | 2.845 (2) | 149 (3) |
O1—H1O···O7 | 0.80 (4) | 1.97 (4) | 2.769 (2) | 178 (3) |
O3—H3O···O7iv | 0.84 (4) | 1.99 (4) | 2.796 (2) | 162 (3) |
O2—H2O···O4v | 0.81 (3) | 2.00 (3) | 2.765 (2) | 159 (3) |
Symmetry codes: (i) x+1, y, z; (ii) −x+2, y−1/2, −z+1; (iii) −x+2, y+1/2, −z+1; (iv) −x+1, y+1/2, −z+1; (v) x−1, y, z. |
Carbon | α-pyranose | β-pyranose | α-furanose | β-furanose | acyclic |
C1 | 52.61 | 52.89 | 51.12 | 52.51 | |
C2 | 99.11 | 98.34 | 104.69 | 101.84 | |
C3 | 73.12 | 72.20 | 85.18 | 80.58 | |
C4 | 74.75 | 72.33 | 78.71 | 77.12 | |
C5 | 68.73 | 71.80 | 85.32 | 83.73 | |
C6 | 65.78 | 66.66 | 63.63 | 64.76 | |
Cα | 75.99 | 76.30 | 76.14 | 76.24 | |
% for (I) | 3.4 | 74.3 | 10.2 | 12.1 | < 0.5 |
% for fructosea | 2.1 | 68.6 | 5.7 | 23.0 | 0.5 |
% for FruLeub | 4 | 72 | 12 | 12 | < 1 |
% for FruAibc | 3.0 | 75.6 | 10.1 | 10.4 | < 0.7 |
% for FruProa | 4.2 | 64.8 | 12.9 | 16.9 | 1.2 |
Notes: (a) Kaufmann et al. (2016); (b) Glinsky et al. (1996); (c) Mossine et al. (2018). |
D—H···A | D—H | H···A | D···A | D—H···A | Symmetry code |
N1—H1A···O7 | 0.91 | 2.40 | 2.702 (2) | 99 | |
N1—H1A···O5 | 0.91 | 2.43 | 2.698 (2) | 97 | |
O2—H2O···O1 | 0.81 (3) | 2.60 (4) | 2.845 (2) | 99 | |
C8—H8A···O8 | 0.99 | 2.47 | 2.810 (3) | 100 | |
C9—H9B···O1 | 0.99 | 2.66 | 3.618 (3) | 162 | x, y, z - 1 |
C11—H11A···O3 | 0.99 | 2.65 | 3.416 (3) | 134 | -x + 2, y - 1/2, -z + 1 |
C4—H4···O4 | 1.00 | 2.69 | 3.364 (3) | 124 | x - 1, y, z |
C6—H6A···O1 | 0.99 | 2.67 | 3.430 (3) | 134 | x + 1, y, z |
Hydrogen-bond selection criteria: D···A < 3.0 Å; H···D < 2.7 Å; D—H···A > 95°. |
Structure | N—C1—C2—O5 torsion (°), conformation | Intramolecular hydrogen bonds around the amino group | No. of intra/inter-molecular hydrogen bonds | % of O···H/H···O contacts on Hirshfeld surface |
Fru-cycloLeu, (I) | +53.3 gt | N1—H1A···O1 (106°); N1—H1A···O5 (97°); N1—H1A···O7 (99°); O1—-H1O···O7 (178°) | 6/5 | 38.5 |
FruGlya | +165.5 tg | N1—H1A···O2 (140°); N1—H1A···O7 (104°) | 2/6 | 51.6 |
FruAib (molecule A)b | +64.7 gt | N1—H1B···O5 (110°); N1—H1B···O7 (107°) | 3/5 | 44.0 |
FruAib (molecule B)b | +176.8 tg | N1—H1A···O2 (145°); N1—H1A···O7 (100°) | 3/5 | 45.9 |
FruPro·H2Od | +75.8 gt | N1—H1···O1 (109°); N1—H1···O7 (125°) | 3/6 | 49.2 |
FruPro·2H2Od | +176.8 tg | N1—H1···O2 (140°); N1—H1···O7 (113°) | 3/6 | 49.3 |
FruPro·MeOHd | +174.4 tg | N1—H1···O2 (139°); N1—H1···O7 (114°) | 4/5 | 40.2 |
FruHis·H2Oe | +60.7 gt | N1—H1B···O5 (100°); N1—H1B···O7 (102°); N1—H1A···O1 (108°) | 5/7 | 41.2 |
Notes: (a) Mossine, Glinsky et al. (1995); (b) Mossine et al. (2018); (c) Mossine et al. (2007a); (d) Tarnawski et al. (2007); (e) Mossine et al. (2007b). |
Acknowledgements
The authors thank Dr Shaokai Jiang for assistance with acquiring the NMR spectra.
Funding information
Funding for this research was provided by: University of Missouri Agriculture Experiment Station Chemical Laboratories; National Institute of Food and Agriculture (grant No. MO-HABC0002).
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