(S)-2-[(4-Fluoro­phen­yl)formamido]-3-phenyl­propanoic acid

Lee, K.S.; Turner, L.; Powell, C.B.; Reinheimer, E.W.

doi:10.1107/S2414314620008974

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 5| Part 7| July 2020| x200897

https://doi.org/10.1107/S2414314620008974

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(S)-2-[(4-Fluorophenyl)formamido]-3-phenylpropanoic acid

Kathleen S. Lee,^a ^* Luke Turner,^a Cynthia B. Powell ^a and Eric W. Reinheimer ^b

^aDepartment of Chemistry and Biochemistry, Abilene Christian University, ACU 28132, Abilene, Texas 79699, USA, and ^bRigaku Americas Corporation, 9009 New Trails Drive, The Woodlands, Texas, 77381, USA
^*Correspondence e-mail: Kathleen.Lee@acu.edu

Edited by M. Weil, Vienna University of Technology, Austria (Received 10 June 2020; accepted 1 July 2020; online 10 July 2020)

The title compound, C₁₆H₁₄FNO₃, was synthesized via solid phase methods; it exhibits monoclinic (P2₁) symmetry at room temperature. The two independent molecules that comprise the asymmetric unit display distinct torsion angles of 173.2 (2) and 72.6 (2)° along the central sp³ C—N bond. In the crystal, hydrogen bonding through N—H⋯O contacts couples the asymmetric unit molecules into pairs that align in layers extending parallel to (100) via additional O—H⋯O interactions. The phenyl ring of one independent molecule was found to be disordered over two sets of sites in a 0.55 (3):0.45 (3) ratio.

Keywords: crystal structure; amino acid derivative; solid phase synthesis; hydrogen bonding.

CCDC reference: 1975451

Structure description

Antibiotic resistance is a major global concern, compounded by the shortage of novel classes of antibiotics in the clinical pipeline (Friedman et al., 2016 ; Frieri et al., 2017 ). In order to address the need for new pharmaceuticals and to incorporate drug discovery into the undergraduate curriculum, William Scott and coworkers created the Distributed Drug Discovery (D3) program (Scott & O'Donnell, 2009 ). D3′s virtual catalogs enumerate sets of amino-acid derivatives that have potential biological activity and that may be synthesized through straightforward combinatorial methods (Scott et al., 2009 ; Abraham et al., 2017 ). The D3 Lab 2 procedure targets N-acyl derivatives of natural amino acids in three steps (Dounay et al., 2019 ). In this paper, we report the use of the D3 procedure to obtain the title compound as a single stereoisomer.

The compound was synthesized via solid phase methods starting from an Fmoc-protected phenylalanine bound to a Wang resin, which was purchased from CreoSalus Advanced Chem Tech as the enantiopure S stereoisomer. The stereocenter remains unchanged during the deprotection, benzoylation, cleavage sequence to form the final product. The absolute configuration of the title compound has been established by anomalous dispersion effects in the diffraction measurement.

Two unique molecules comprise the asymmetric unit. Within the molecules the planes containing the benzene rings are rotated with respect to one another by 79.9 (1)° (molecule 1, containing N1—F1) and 89.3 (1)° (molecule 2, containing N2—F2), as shown in Fig. 1. The phenyl ring in molecule 1 is disordered over two slightly different positions. Interestingly, torsion angles measured at the middle of the molecules are quite different; in molecule 1, the C1—N1—C9—C10 angle is 173.2 (2)° and in molecule 2, the analogous C17—N2—C25—C26 angle is 72.6 (2)°. The amino-hydrogen atom on each molecule is hydrogen-bonded to the organic-acid carbonyl O atom on the other molecule (N—H⋯O contacts, Table 1) coupling the molecules in the asymmetric unit so that they are positioned on top of each other with a fluoro-substituted ring above and nearly perpendicular to the unsubstituted ring of the partner molecule [mean dihedral angle between the rings of the two molecules = 87 (3)°]. Fig. 2 shows an overlay of the two distinct molecules, highlighting their conformational differences. As shown in Fig. 3, the coupled asymmetric-unit pairs align in chains parallel to [010] via additional hydrogen-bonding interactions between OH organic-acid hydrogen atoms and the amide oxygen atoms in adjacent pairs through the O—H⋯O contacts listed in Table 1. Layers of chains extending parallel to (100) are visible when the packing is viewed along the b axis. The benzene-ring ends of the asymmetric-unit pairs that project out of each hydrogen-bonded chain occupy the voids between coupled asymmetric-unit pairs in the chain layers above and below, allowing closer packing.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5⋯O6ⁱ	0.84	1.83	2.6497 (18)	163
O1—H1⋯O3ⁱⁱ	0.84	1.77	2.607 (2)	177
N1—H1A⋯O4	0.89 (2)	2.16 (2)	3.039 (2)	170 (2)
N2—H2⋯O2	0.84 (2)	2.06 (2)	2.900 (2)	170 (2)
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+2]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+1]$ .

Figure 1
The asymmetric unit consists of two molecules of the title compound, shown here with displacement ellipsoids drawn at the 50% probability level. The minor component of the disordered phenyl ring is shown in pale blue.

Figure 2
An overlay illustration of the two independent molecules. For molecule 1 only the major component of the disordered phenyl ring is displayed; molecule 2 is shown in purple.

Figure 3
The packing of the molecules of the title compound in a view along the b axis, showing hydrogen-bonded layers parallel to (100).

Synthesis and crystallization

50 µmol of S-phenylalanine protected with fluorenylmethyloxycarbonyl (Fmoc) and bound to a Wang resin were placed in a fritted vial with screw caps at both ends. The resin was rinsed with three 3 ml aliquots of N-methyl-2-pyrrolidone (NMP) and three 2 ml aliquots of NMP:piperidine (4:1). The bottom of the vial was capped to prevent the acylating reagents from draining from the vial. To the resin was added 1.0 ml of a solution of p-fluorobenzoic acid (0.25 M) and hydroxybenzotriazole (HOBt, 0.25 M) in NMP and 0.5 ml of 0.5 M diisopropylcarbodiimide in NMP. The vial was capped, inverted three times, and allowed to sit. After four days, the vial was uncapped at both ends, and the resin was washed sequentially with two 3 ml portions of NMP, two 3 ml portions of tetrahydrofuran, and three 3 ml portions of dichloromethane. The reaction vial was placed over a collection vial, and the resin was washed twice with 2.0 ml of trifluoroacetic acid–dichloromethane–water (35:60:5) and once with 2.0 ml of dichloromethane. The collection vial containing the combined rinses was placed in a vacuum chamber to remove the solvents. Column chromatography (hexanes:acetone, 75/25 v/v) afforded 12.8 mg of the title compound (89% overall yield from Fmoc–Phe–Wang resin). The purified product was crystallized from a dichloromethane solution layered with a solution of heptane and benzene. ¹H NMR (600 MHz, CDCl₃/CD₃OD) δ 7.73 (m, 2H), 7.13 (m, 3H), 7.10 (m, 4H), 5.05 (t, J = 5.6 Hz, 1H), 3.27 (dd, J = 13.8, 5.7 Hz, 1H), 3.21 (dd, J = 13.8, 5.6 Hz, 1H). ¹³C NMR (150 MHz, CDCl₃/CD₃OD) δ 172.23, 166.11, 164.09, 135.77, 129.49, 129.43, 129.29, 128.67, 127.26, 115.78, 53.55, 37.78.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The phenyl ring (C11–C16) of molecule 1 was found to be disordered over two sets of sites in a ratio of 0.55 (3):0.45 (3). The AFIX 66 constraint was applied to both parts of the disordered phenyl ring, and the RIGU rigid body restraint was applied to all non-hydrogen atoms in those rings with σ values of 0.001 for the 1–2 and 1–3 distances.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₆H₁₄FNO₃
M_r	287.28
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	100
a, b, c (Å)	9.74134 (5), 9.83313 (4), 14.91737 (6)
β (°)	98.2662 (4)
V (Å³)	1414.06 (1)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.86
Crystal size (mm)	0.56 × 0.21 × 0.12

Data collection
Diffractometer	Rigaku Oxford Diffraction SuperNova, Dual, Cu at home/near, AtlasS2
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2019 )
T_min, T_max	0.452, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	53742, 5671, 5602
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.622

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.028, 0.079, 1.05
No. of reflections	5671
No. of parameters	421
No. of restraints	355
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.16, −0.12
Absolute structure	Flack x determined using 2580 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.05 (3)
Computer programs: CrysAlis PRO (Rigaku OD, 2019), SHELXT (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ), OLEX2 (Dolomanov et al., 2009 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1975451

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314620008974/wm4133sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2414314620008974/wm4133Isup2.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2019); cell refinement: CrysAlis PRO (Rigaku OD, 2019); data reduction: CrysAlis PRO (Rigaku OD, 2019); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

(S)-2-[(4-Fluorophenyl)formamido]-3-phenylpropanoic acid top

Crystal data top

C₁₆H₁₄FNO₃	F(000) = 600
M_r = 287.28	D_x = 1.349 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54184 Å
a = 9.74134 (5) Å	Cell parameters from 40752 reflections
b = 9.83313 (4) Å	θ = 4.6–73.5°
c = 14.91737 (6) Å	µ = 0.86 mm⁻¹
β = 98.2662 (4)°	T = 100 K
V = 1414.06 (1) Å³	Block, colourless
Z = 4	0.56 × 0.21 × 0.12 mm

Data collection top

Rigaku Oxford Diffraction SuperNova, Dual, Cu at home/near, AtlasS2 diffractometer	5671 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source	5602 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.032
Detector resolution: 5.2387 pixels mm^-1	θ_max = 73.7°, θ_min = 4.6°
ω scans	h = −11→12
Absorption correction: gaussian (CrysAlis PRO; Rigaku OD, 2019)	k = −12→12
T_min = 0.452, T_max = 1.000	l = −18→18
53742 measured reflections

Refinement top

Refinement on F²	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0473P)² + 0.1344P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.028	(Δ/σ)_max = 0.001
wR(F²) = 0.079	Δρ_max = 0.16 e Å⁻³
S = 1.05	Δρ_min = −0.12 e Å⁻³
5671 reflections	Extinction correction: SHELXL-2014/7 (Sheldrick 2014, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
421 parameters	Extinction coefficient: 0.0068 (5)
355 restraints	Absolute structure: Flack x determined using 2580 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
Primary atom site location: dual	Absolute structure parameter: −0.05 (3)
Hydrogen site location: mixed

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O4	0.55896 (13)	0.60198 (15)	0.89050 (9)	0.0473 (3)
O5	0.38969 (13)	0.57893 (16)	0.97497 (8)	0.0464 (3)
H5	0.4369	0.6359	1.0082	0.070*
O3	0.47124 (17)	0.78037 (16)	0.57577 (9)	0.0532 (4)
O2	0.49339 (14)	0.45890 (15)	0.60468 (9)	0.0477 (3)
N2	0.43835 (15)	0.38567 (14)	0.78447 (10)	0.0362 (3)
O6	0.51088 (15)	0.27881 (15)	0.91538 (8)	0.0474 (3)
O1	0.64625 (15)	0.49117 (17)	0.50928 (9)	0.0543 (4)
H1	0.6083	0.4219	0.4837	0.081*
F1	0.14855 (17)	1.06807 (19)	0.85687 (12)	0.0825 (5)
F2	0.83586 (18)	−0.06630 (18)	0.65856 (14)	0.0876 (5)
N1	0.59204 (17)	0.69008 (16)	0.69952 (10)	0.0401 (3)
C18	0.59847 (18)	0.19811 (17)	0.78350 (12)	0.0387 (4)
C25	0.35323 (17)	0.48177 (16)	0.82684 (10)	0.0334 (3)
H25	0.3192	0.5505	0.7794	0.040*
C8	0.59457 (18)	0.51500 (18)	0.58414 (11)	0.0370 (3)
C24	0.44635 (16)	0.55878 (17)	0.90178 (10)	0.0334 (3)
C17	0.51291 (18)	0.28963 (17)	0.83285 (11)	0.0360 (3)
C23	0.5622 (2)	0.16621 (18)	0.69210 (14)	0.0439 (4)
H23	0.4815	0.2053	0.6587	0.053*
C1	0.4897 (2)	0.76851 (18)	0.65954 (11)	0.0399 (4)
C27	0.11085 (18)	0.50384 (19)	0.87908 (11)	0.0380 (3)
C2	0.3995 (2)	0.84212 (18)	0.71611 (12)	0.0408 (4)
C26	0.22470 (19)	0.41301 (18)	0.85338 (13)	0.0421 (4)
H26A	0.1839	0.3551	0.8021	0.050*
H26B	0.2551	0.3519	0.9052	0.050*
C22	0.6434 (2)	0.0778 (2)	0.64961 (16)	0.0532 (5)
H22	0.6198	0.0564	0.5872	0.064*
C32	−0.0009 (2)	0.4410 (2)	0.91043 (13)	0.0488 (4)
H32	−0.0039	0.3446	0.9139	0.059*
C9	0.67988 (19)	0.61896 (19)	0.64353 (11)	0.0383 (4)
H9	0.7187	0.6866	0.6038	0.046*
C19	0.7173 (2)	0.1409 (2)	0.83170 (15)	0.0495 (4)
H19	0.7435	0.1631	0.8938	0.059*
C10	0.8002 (2)	0.5494 (2)	0.70428 (12)	0.0483 (4)
H10C	0.8406	0.6155	0.7507	0.058*	0.45 (3)
H10D	0.7619	0.4732	0.7363	0.058*	0.45 (3)
H10A	0.7621	0.4755	0.7385	0.058*	0.55 (3)
H10B	0.8443	0.6165	0.7488	0.058*	0.55 (3)
C21	0.7572 (2)	0.0226 (2)	0.69956 (18)	0.0567 (5)
C28	0.1109 (2)	0.6446 (2)	0.87296 (14)	0.0457 (4)
H28	0.1847	0.6897	0.8500	0.055*
C31	−0.1082 (2)	0.5172 (3)	0.93667 (15)	0.0586 (5)
H31	−0.1840	0.4727	0.9577	0.070*
C4	0.3585 (2)	0.9521 (2)	0.85435 (15)	0.0539 (5)
H4	0.3875	0.9752	0.9160	0.065*
C7	0.2683 (2)	0.8821 (2)	0.67540 (14)	0.0514 (4)
H7	0.2366	0.8567	0.6145	0.062*
C29	0.0034 (2)	0.7198 (2)	0.90028 (15)	0.0553 (5)
H29	0.0051	0.8163	0.8966	0.066*
C3	0.4435 (2)	0.8773 (2)	0.80636 (13)	0.0461 (4)
H3	0.5325	0.8497	0.8350	0.055*
C16B	0.9064 (12)	0.3556 (8)	0.6455 (9)	0.063 (2)	0.45 (3)
H16B	0.8344	0.3050	0.6667	0.076*	0.45 (3)
C15B	1.0046 (15)	0.2896 (8)	0.6023 (8)	0.071 (2)	0.45 (3)
H15B	0.9998	0.1938	0.5939	0.085*	0.45 (3)
C14B	1.1099 (13)	0.3636 (14)	0.5712 (6)	0.064 (2)	0.45 (3)
H14B	1.1770	0.3184	0.5417	0.077*	0.45 (3)
C13B	1.1169 (8)	0.5037 (13)	0.5835 (7)	0.073 (2)	0.45 (3)
H13B	1.1889	0.5543	0.5623	0.087*	0.45 (3)
C12B	1.0187 (10)	0.5698 (8)	0.6268 (7)	0.054 (2)	0.45 (3)
H12B	1.0235	0.6655	0.6351	0.065*	0.45 (3)
C11B	0.9134 (10)	0.4957 (8)	0.6578 (9)	0.0461 (19)	0.45 (3)
C6	0.1834 (2)	0.9586 (3)	0.72273 (17)	0.0600 (5)
H6	0.0943	0.9871	0.6948	0.072*
C5	0.2313 (2)	0.9922 (2)	0.81097 (16)	0.0565 (5)
C20	0.7975 (2)	0.0519 (3)	0.78943 (18)	0.0608 (5)
H20	0.8785	0.0119	0.8219	0.073*
C30	−0.1054 (2)	0.6563 (3)	0.93251 (15)	0.0580 (5)
H30	−0.1780	0.7084	0.9517	0.070*
C16A	1.0068 (9)	0.5848 (5)	0.6299 (7)	0.068 (3)	0.55 (3)
H16A	0.9943	0.6783	0.6424	0.082*	0.55 (3)
C15A	1.1190 (7)	0.5437 (10)	0.5885 (6)	0.0672 (17)	0.55 (3)
H15A	1.1832	0.6092	0.5728	0.081*	0.55 (3)
C14A	1.1373 (7)	0.4068 (12)	0.5702 (5)	0.0602 (16)	0.55 (3)
H14A	1.2140	0.3788	0.5419	0.072*	0.55 (3)
C13A	1.0434 (10)	0.3110 (7)	0.5931 (6)	0.0617 (17)	0.55 (3)
H13A	1.0559	0.2175	0.5806	0.074*	0.55 (3)
C12A	0.9312 (9)	0.3521 (6)	0.6345 (7)	0.0571 (16)	0.55 (3)
H12A	0.8670	0.2866	0.6502	0.068*	0.55 (3)
C11A	0.9129 (8)	0.4889 (7)	0.6528 (7)	0.0437 (15)	0.55 (3)
H1A	0.594 (2)	0.665 (2)	0.7566 (16)	0.047 (6)*
H2	0.452 (2)	0.397 (2)	0.7303 (16)	0.044 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0360 (6)	0.0599 (8)	0.0469 (7)	−0.0066 (5)	0.0088 (5)	−0.0043 (6)
O5	0.0425 (6)	0.0618 (8)	0.0359 (6)	−0.0085 (6)	0.0089 (5)	−0.0125 (6)
O3	0.0718 (10)	0.0542 (8)	0.0339 (6)	0.0109 (7)	0.0087 (6)	0.0057 (6)
O2	0.0519 (7)	0.0538 (8)	0.0388 (6)	−0.0108 (6)	0.0115 (5)	−0.0034 (5)
N2	0.0439 (8)	0.0371 (7)	0.0288 (6)	0.0068 (6)	0.0089 (5)	0.0016 (5)
O6	0.0582 (8)	0.0501 (7)	0.0348 (6)	0.0137 (6)	0.0094 (5)	0.0083 (5)
O1	0.0544 (8)	0.0741 (10)	0.0366 (6)	−0.0145 (7)	0.0135 (6)	−0.0184 (6)
F1	0.0859 (10)	0.0780 (10)	0.0923 (10)	0.0130 (8)	0.0431 (8)	−0.0129 (9)
F2	0.0745 (10)	0.0735 (10)	0.1229 (13)	0.0176 (8)	0.0420 (9)	−0.0265 (9)
N1	0.0499 (8)	0.0421 (7)	0.0286 (6)	−0.0001 (6)	0.0073 (6)	−0.0007 (6)
C18	0.0401 (8)	0.0325 (7)	0.0448 (8)	0.0001 (6)	0.0108 (6)	0.0036 (6)
C25	0.0363 (7)	0.0331 (7)	0.0308 (7)	0.0035 (6)	0.0052 (6)	0.0006 (6)
C8	0.0404 (8)	0.0428 (8)	0.0277 (7)	0.0012 (6)	0.0043 (6)	0.0015 (6)
C24	0.0333 (7)	0.0344 (7)	0.0324 (7)	0.0032 (6)	0.0047 (6)	0.0013 (6)
C17	0.0383 (8)	0.0346 (7)	0.0356 (7)	0.0000 (6)	0.0066 (6)	0.0027 (6)
C23	0.0464 (9)	0.0369 (8)	0.0492 (9)	0.0001 (7)	0.0104 (7)	−0.0049 (7)
C1	0.0498 (9)	0.0356 (8)	0.0347 (7)	−0.0046 (7)	0.0076 (6)	0.0018 (6)
C27	0.0348 (8)	0.0444 (8)	0.0340 (8)	−0.0006 (6)	0.0021 (6)	−0.0025 (6)
C2	0.0494 (9)	0.0346 (8)	0.0397 (8)	−0.0052 (7)	0.0108 (6)	0.0021 (6)
C26	0.0385 (8)	0.0357 (8)	0.0528 (10)	−0.0026 (6)	0.0095 (7)	−0.0025 (7)
C22	0.0548 (10)	0.0434 (9)	0.0649 (11)	−0.0047 (8)	0.0206 (8)	−0.0140 (9)
C32	0.0439 (9)	0.0611 (11)	0.0419 (9)	−0.0029 (8)	0.0078 (7)	0.0062 (8)
C9	0.0429 (8)	0.0433 (8)	0.0290 (7)	−0.0032 (7)	0.0067 (6)	−0.0016 (6)
C19	0.0444 (9)	0.0516 (10)	0.0537 (10)	0.0078 (8)	0.0111 (8)	0.0080 (8)
C10	0.0443 (9)	0.0643 (11)	0.0348 (8)	0.0009 (8)	0.0012 (7)	−0.0016 (8)
C21	0.0515 (10)	0.0446 (10)	0.0796 (12)	0.0025 (8)	0.0283 (9)	−0.0072 (9)
C28	0.0397 (9)	0.0441 (9)	0.0533 (10)	0.0010 (7)	0.0064 (8)	−0.0053 (7)
C31	0.0433 (10)	0.0867 (13)	0.0474 (10)	0.0006 (9)	0.0124 (8)	−0.0001 (10)
C4	0.0642 (11)	0.0496 (10)	0.0509 (10)	−0.0098 (8)	0.0190 (8)	−0.0115 (8)
C7	0.0518 (10)	0.0580 (11)	0.0453 (9)	−0.0001 (8)	0.0104 (7)	0.0068 (8)
C29	0.0485 (10)	0.0570 (11)	0.0589 (12)	0.0110 (8)	0.0026 (9)	−0.0134 (9)
C3	0.0527 (10)	0.0421 (9)	0.0443 (9)	−0.0075 (8)	0.0093 (7)	−0.0043 (7)
C16B	0.066 (4)	0.057 (3)	0.071 (4)	0.003 (2)	0.024 (3)	−0.004 (2)
C15B	0.075 (5)	0.055 (3)	0.090 (4)	0.002 (2)	0.036 (4)	−0.002 (3)
C14B	0.072 (4)	0.049 (4)	0.078 (4)	0.004 (3)	0.033 (3)	−0.004 (3)
C13B	0.075 (3)	0.050 (4)	0.103 (5)	0.000 (3)	0.049 (4)	−0.005 (3)
C12B	0.052 (3)	0.053 (3)	0.058 (4)	0.001 (2)	0.014 (3)	−0.006 (2)
C11B	0.045 (3)	0.057 (3)	0.036 (4)	0.0017 (18)	0.002 (3)	−0.002 (2)
C6	0.0547 (11)	0.0649 (13)	0.0633 (11)	0.0081 (10)	0.0183 (9)	0.0095 (9)
C5	0.0616 (11)	0.0490 (10)	0.0643 (11)	−0.0014 (9)	0.0274 (9)	−0.0010 (9)
C20	0.0477 (10)	0.0570 (11)	0.0810 (13)	0.0138 (9)	0.0205 (9)	0.0074 (10)
C30	0.0442 (10)	0.0827 (13)	0.0471 (10)	0.0104 (9)	0.0070 (8)	−0.0144 (9)
C16A	0.063 (3)	0.057 (3)	0.092 (6)	−0.006 (2)	0.031 (4)	−0.006 (2)
C15A	0.063 (3)	0.056 (3)	0.088 (4)	−0.009 (2)	0.029 (3)	−0.007 (2)
C14A	0.056 (3)	0.057 (3)	0.071 (3)	−0.008 (2)	0.023 (2)	−0.002 (3)
C13A	0.059 (3)	0.048 (2)	0.083 (4)	−0.0027 (19)	0.029 (2)	0.000 (2)
C12A	0.054 (3)	0.049 (2)	0.072 (4)	−0.0034 (16)	0.023 (3)	−0.0009 (18)
C11A	0.041 (2)	0.051 (2)	0.037 (3)	−0.0016 (15)	−0.001 (2)	−0.0007 (18)

Geometric parameters (Å, º) top

O4—C24	1.210 (2)	C10—H10A	0.9900
O5—H5	0.8400	C10—H10B	0.9900
O5—C24	1.307 (2)	C10—C11B	1.482 (6)
O3—C1	1.242 (2)	C10—C11A	1.546 (5)
O2—C8	1.207 (2)	C21—C20	1.372 (4)
N2—C25	1.460 (2)	C28—H28	0.9500
N2—C17	1.338 (2)	C28—C29	1.391 (3)
N2—H2	0.84 (2)	C31—H31	0.9500
O6—C17	1.239 (2)	C31—C30	1.369 (4)
O1—H1	0.8400	C4—H4	0.9500
O1—C8	1.310 (2)	C4—C3	1.382 (3)
F1—C5	1.354 (3)	C4—C5	1.371 (3)
F2—C21	1.364 (2)	C7—H7	0.9500
N1—C1	1.332 (2)	C7—C6	1.384 (3)
N1—C9	1.457 (2)	C29—H29	0.9500
N1—H1A	0.89 (2)	C29—C30	1.375 (3)
C18—C17	1.491 (2)	C3—H3	0.9500
C18—C23	1.394 (3)	C16B—H16B	0.9500
C18—C19	1.390 (3)	C16B—C15B	1.3900
C25—H25	1.0000	C16B—C11B	1.3900
C25—C24	1.534 (2)	C15B—H15B	0.9500
C25—C26	1.525 (2)	C15B—C14B	1.3900
C8—C9	1.520 (2)	C14B—H14B	0.9500
C23—H23	0.9500	C14B—C13B	1.3900
C23—C22	1.388 (3)	C13B—H13B	0.9500
C1—C2	1.490 (3)	C13B—C12B	1.3900
C27—C26	1.516 (3)	C12B—H12B	0.9500
C27—C32	1.390 (3)	C12B—C11B	1.3900
C27—C28	1.387 (3)	C6—H6	0.9500
C2—C7	1.391 (3)	C6—C5	1.372 (3)
C2—C3	1.396 (3)	C20—H20	0.9500
C26—H26A	0.9900	C30—H30	0.9500
C26—H26B	0.9900	C16A—H16A	0.9500
C22—H22	0.9500	C16A—C15A	1.3900
C22—C21	1.357 (3)	C16A—C11A	1.3900
C32—H32	0.9500	C15A—H15A	0.9500
C32—C31	1.388 (3)	C15A—C14A	1.3900
C9—H9	1.0000	C14A—H14A	0.9500
C9—C10	1.536 (3)	C14A—C13A	1.3900
C19—H19	0.9500	C13A—H13A	0.9500
C19—C20	1.384 (3)	C13A—C12A	1.3900
C10—H10C	0.9900	C12A—H12A	0.9500
C10—H10D	0.9900	C12A—C11A	1.3900

C24—O5—H5	109.5	C11A—C10—H10B	108.6
C25—N2—H2	120.2 (16)	F2—C21—C20	118.2 (2)
C17—N2—C25	121.44 (14)	C22—C21—F2	118.5 (2)
C17—N2—H2	117.7 (16)	C22—C21—C20	123.3 (2)
C8—O1—H1	109.5	C27—C28—H28	119.9
C1—N1—C9	118.99 (14)	C27—C28—C29	120.3 (2)
C1—N1—H1A	120.1 (15)	C29—C28—H28	119.9
C9—N1—H1A	119.1 (15)	C32—C31—H31	119.8
C23—C18—C17	122.54 (16)	C30—C31—C32	120.4 (2)
C19—C18—C17	118.14 (17)	C30—C31—H31	119.8
C19—C18—C23	119.32 (17)	C3—C4—H4	120.8
N2—C25—H25	106.4	C5—C4—H4	120.8
N2—C25—C24	108.77 (13)	C5—C4—C3	118.5 (2)
N2—C25—C26	111.36 (14)	C2—C7—H7	119.7
C24—C25—H25	106.4	C6—C7—C2	120.7 (2)
C26—C25—H25	106.4	C6—C7—H7	119.7
C26—C25—C24	116.82 (14)	C28—C29—H29	119.6
O2—C8—O1	124.23 (16)	C30—C29—C28	120.8 (2)
O2—C8—C9	123.89 (15)	C30—C29—H29	119.6
O1—C8—C9	111.86 (15)	C2—C3—H3	119.7
O4—C24—O5	124.25 (16)	C4—C3—C2	120.5 (2)
O4—C24—C25	121.64 (15)	C4—C3—H3	119.7
O5—C24—C25	114.01 (14)	C15B—C16B—H16B	120.0
N2—C17—C18	117.28 (14)	C15B—C16B—C11B	120.0
O6—C17—N2	120.79 (16)	C11B—C16B—H16B	120.0
O6—C17—C18	121.93 (15)	C16B—C15B—H15B	120.0
C18—C23—H23	119.8	C14B—C15B—C16B	120.0
C22—C23—C18	120.45 (19)	C14B—C15B—H15B	120.0
C22—C23—H23	119.8	C15B—C14B—H14B	120.0
O3—C1—N1	119.71 (17)	C15B—C14B—C13B	120.0
O3—C1—C2	120.83 (17)	C13B—C14B—H14B	120.0
N1—C1—C2	119.46 (15)	C14B—C13B—H13B	120.0
C32—C27—C26	117.39 (17)	C12B—C13B—C14B	120.0
C28—C27—C26	124.34 (17)	C12B—C13B—H13B	120.0
C28—C27—C32	118.28 (19)	C13B—C12B—H12B	120.0
C7—C2—C1	118.01 (17)	C13B—C12B—C11B	120.0
C7—C2—C3	119.05 (19)	C11B—C12B—H12B	120.0
C3—C2—C1	122.88 (18)	C16B—C11B—C10	112.9 (6)
C25—C26—H26A	107.9	C12B—C11B—C10	127.1 (6)
C25—C26—H26B	107.9	C12B—C11B—C16B	120.0
C27—C26—C25	117.55 (15)	C7—C6—H6	120.8
C27—C26—H26A	107.9	C5—C6—C7	118.4 (2)
C27—C26—H26B	107.9	C5—C6—H6	120.8
H26A—C26—H26B	107.2	F1—C5—C4	118.9 (2)
C23—C22—H22	120.9	F1—C5—C6	118.3 (2)
C21—C22—C23	118.3 (2)	C4—C5—C6	122.9 (2)
C21—C22—H22	120.9	C19—C20—H20	120.8
C27—C32—H32	119.6	C21—C20—C19	118.5 (2)
C31—C32—C27	120.8 (2)	C21—C20—H20	120.8
C31—C32—H32	119.6	C31—C30—C29	119.4 (2)
N1—C9—C8	109.88 (14)	C31—C30—H30	120.3
N1—C9—H9	108.9	C29—C30—H30	120.3
N1—C9—C10	109.69 (14)	C15A—C16A—H16A	120.0
C8—C9—H9	108.9	C15A—C16A—C11A	120.0
C8—C9—C10	110.57 (16)	C11A—C16A—H16A	120.0
C10—C9—H9	108.9	C16A—C15A—H15A	120.0
C18—C19—H19	119.9	C14A—C15A—C16A	120.0
C20—C19—C18	120.2 (2)	C14A—C15A—H15A	120.0
C20—C19—H19	119.9	C15A—C14A—H14A	120.0
C9—C10—H10C	108.3	C15A—C14A—C13A	120.0
C9—C10—H10D	108.3	C13A—C14A—H14A	120.0
C9—C10—H10A	108.6	C14A—C13A—H13A	120.0
C9—C10—H10B	108.6	C12A—C13A—C14A	120.0
C9—C10—C11A	114.5 (5)	C12A—C13A—H13A	120.0
H10C—C10—H10D	107.4	C13A—C12A—H12A	120.0
H10A—C10—H10B	107.6	C13A—C12A—C11A	120.0
C11B—C10—C9	116.0 (6)	C11A—C12A—H12A	120.0
C11B—C10—H10C	108.3	C16A—C11A—C10	113.7 (5)
C11B—C10—H10D	108.3	C12A—C11A—C10	126.2 (5)
C11A—C10—H10A	108.6	C12A—C11A—C16A	120.0

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O6ⁱ	0.84	1.83	2.6497 (18)	163
O1—H1···O3ⁱⁱ	0.84	1.77	2.607 (2)	177
N1—H1A···O4	0.89 (2)	2.16 (2)	3.039 (2)	170 (2)
N2—H2···O2	0.84 (2)	2.06 (2)	2.900 (2)	170 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+2; (ii) −x+1, y−1/2, −z+1.

Acknowledgements

NMR data were collected by Dr Joseph Ready and Dr Feng Lin at UT Southwestern Medical Center, Dallas, Texas.

Funding information

Funding for this research was provided by: The Welch Foundation (grant No. R-0021); Abilene Christian University Office of Undergraduate Research; Abilene Christian University Research Council.

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