Crystal Structure of Methyl 4-Acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-ß-D-allopyranoside
by
Miroslav Koóš
1,*, 
Bohumil Steiner
1,
Ján Gajdoš
1,
Vratislav Langer
2,
Dalma Gyepesová
3,
L'ubomìr Smrčok
3 and
Marián Ďurík
3 1
Institute of Chemistry, Slovak Academy of Sciences, SK-84238 Bratislava, Slovak Republic
2
Department of Inorganic Environmental Chemistry, Chalmers University of Technology, SE-41296 Göteborg, Sweden
3
Institute of Inorganic Chemistry, Slovak Academy of Sciences, SK-84236 Bratislava, Slovak Republic
*
Author to whom correspondence should be addressed.
Molecules 2000, 5(3), 219-226; https://doi.org/10.3390/50300219
Submission received: 17 February 2000
/
Accepted: 28 February 2000
/
Published: 2 March 2000
Abstract
:The detailed structure of methyl 4-acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-β-D-allopyranoside was established by X-ray analysis confirming allo configuration at C-4 and suggesting a 4C1 conformation of the pyranose ring. The values of relevant torsion angles and calculated puckering parameters revealed a distortion into the direction of 0H5, thus indicating a flattening at C-1 and C-4.
Introduction
With respect to biological and medicinal importance, amino sugars represent a significant group of organic compounds. To understand the mechanism of their biological activity, a lot of suitable synthetically prepared model compounds with well established structure are needed.
In our previous paper [1], we have described the preparation of two sugar amino nitriles – methyl 4-amino-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-α-L-talopyranoside (1) and 4-amino-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-β-D-allopyranoside (2) which are structurally related to naturally occurring biologically important Perosamine (3) (Figure 1). Because of the difficulties in unambiguous establishing the configuration at C-4 position of the pyranose ring (allo versus gulo) by NMR methods, suitable crystals of corresponding N-acetylated compounds 4 and 5 were subjected to X-ray analysis.
Since the crystal and molecular structure determination of 4 by NMR and X-ray methods has already been published [1], we now wish to present the X-ray analysis of acetylated amino nitrile 5.
Results and Discussion
Synthesis
The amino nitrile 2 was synthesized either from 4-uloses 6 or 7 using slightly modified Strecker reaction conditions (Scheme 1) or alternatively from cyanohydrin 8 (ammonia and ammonium chloride as reactants) as described in [1]. Subsequent acetylation (acetic anhydride, pyridine) afforded the title compound 5 [1].
Structure Elucidation
The title compound 5 was fully characterized by 1H and 13C NMR, EIMS, CIMS, [α]D, TLC, mp and elemental analysis data [1]. The coupling constants J1,2 of 6.9 Hz and J2,3 of 5.2 Hz (in comparison with J1,2 of 0 Hz and J2,3 of 6.3 Hz reported for 1C4 conformation of 4) suggested an inversion of a 1C4 to a 4C1 conformation with an equatorial glycosidic methoxyl group and H-3, an axial H-5 and H-2 and favoured 2,3-cis stereochemistry for the isopropylidene group (similar base-catalyzed isomerizations with inversion at C-5 and unchanged configuration at C-3 were observed previously [2,3]) indicating the possibility of either β-D-allo or β-D-gulo configuration. Because the data obtained from NMR measurements were unsufficient, X-ray analysis was used to determine unambiguously correct actual configuration and simultaneously, conformation of the pyranose ring.
X-ray Analysis
The suitable crystals were obtained by slow crystallization from a mixture of ethyl acetate–hexane (1:2, v/v) at room temperature. The relevant crystallographic data and structure refinement are given in Table 1. The bond lengths and bond angles are listed in Table 2. A list of selected torsion angles is given in Table 3. The final positional parameters are summarized in Table 4. Perspective view and the numbering of the atoms is depicted in Figure 2. The hydrogen atoms were refined isotropically in idealized positions riding on the atom to which they are attached.
The analysis of ring conformation by calculating puckering parameters [Q = 0.544(4) Å, θ = 22.9 (5)°, φ = 326.9(13)°] according to Cremer and Pople [4] has shown that pyranose ring in 5 adopt a 4C1 conformation which is slightly distorted into the direction of 0H5 [5,6], thus indicating a flattening at C-1 and C-4.
The values of relevant torsion angles [O3–C3–C4–C11 = 170.0(3)°, C3–C4–C5–C6 = –177.8(4)°] clearly demonstrate an allo configuration respecting the above mentioned conformation of the pyranose ring. On the other hand, torsion angle O1–C1–C2–O2 = –84.7(4)° suggests a β-D-anomeric linkage. Additionally, the values of torsion angles H1–C1–C2–H2 = 156.2(5)° and H2–C2–C3–H3 = –35.0(7)° obtained from X-ray analysis are in good agreement with those obtained from 1H NMR measurements. According to Karplus curve [7], observed vicinal coupling constants J1,2 = 6.9 Hz and J2,3 = 5.2 Hz correlate with dihedral angles of 154° and 36°, respectively.
Experimental
General
The relevant data of synthetic and analytical methods as well as instruments and materials used for the preparation and characterization of the title compound are presented in ref. [1]. Analytical sample of 5 was used for generation of suitable crystals.
X-ray Analysis
Crystal and experimental data for compound 5 are given in Table 1. The structure was solved by direct methods and refined by anisotropic full-matrix least-squares technique. The choice of space group and hence the absolute configuration of the compound (1-R, 2-R, 3-R, 4-R, 5-R) was based on the fact that configuration on positions 1, 2, 3 and 5 of pyranose ring is known and could not change. The crystallographic computations were performed with Bruker SHELXTL [8]. The ZORTEP program [9] was used for the molecular graphics drawing.
Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre. The corresponding deposition number is CCDC 140110. Copies of the data can be obtained free of charge on request to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Tel.: +44-1223-336408, Fax: +44-1223 336-033).
Acknowledgements
Financial support of this work by the Scientific Grant Agency (VEGA, Slovak Academy of Sciences and Ministry of Education, Bratislava, projects No. 2/4144/99, 2/7144/20 and 2/7204/20) is gratefully appreciated.
References and Notes
- Steiner, B.; Kóǒs, M.; Langer, V.; Gyepesová, D.; Smrčok, L. 4-Amino-4-cyano-4,6-dideoxy Sugar Derivatives from Methyl 6-deoxy-2,3-O-isopropylidene-α-L-lyxo-hexopyranosid-4-ulose via Strecker-type Reaction. Carbohydr. Res. 1998, 311, 1–9. [Google Scholar] [CrossRef]
- Horton, D.; Just, E.K. Stereospecific chain-branching by C-alkylation at the ketonic and enolic positions of 1,6-anhydro-2,3-O-isopropylidene-β-D-lyxo-hexopyranos-4-ulose. Carbohydr. Res. 1971, 18, 81–94. [Google Scholar] [CrossRef]
- Stevens, C.L.; Balasubramanian, K.K.; Bryant, Ch.P.; Filippi, J.B.; Pillai, P.M. J. Org. Chem. 1973, 38, 4311–4318. [CrossRef]
- Cremer, D.; Pople, J. A. A General Definition of Ring Puckering Coordinates. J. Am. Chem. Soc. 1975, 97, 1354–1358. [Google Scholar] [CrossRef]
- Köll, P.; Saak, W.; Pohl, S.; Steiner, B.; Koóš, M. Preparation and crystal and molecular structure of 6-O-[(2S)-2,3-epoxypropyl]-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose. Pyranoid ring conformation in 1,2:3,4-di-O-isopropylidene-galactopyranose and related systems. Carbohydr. Res. 1994, 265, 237–248. [Google Scholar] [CrossRef]
- Boeyens, J.C.A. The conformation of six-membered rings. J. Cryst. Mol. Struct. 1978, 8, 317–320. [Google Scholar] [CrossRef]
- Hesse, M.; Meier, H.; Zeeh, B. Spectroscopic Methods in Organic Chemistry; Enders, D., Noyori, R., Trost, B.M., Eds.; Georg Thieme Verlag Stuttgart: New York, 1997; p. 108. [Google Scholar]
- Bruker AXS Inc. SHELXTL Version 5.10, Madison, Wisconsin: USA, 1997.
- Zsolnai, L.; Huttner, G. Program ZORTEP; University of Heidelberg: Germany, 1994. [Google Scholar]
- Samples Availability: Available from the authors.
Figure 1.
Scheme 1.
Figure 2.
ZORTEP plot and atomic numbering of compound 5.
| Empirical formula | C13H20N2O5 |
| Formula weight | 284.31 |
| Temperature, T (K) | 296(2) |
| Wavelength, λ (Å) | 0.71073 |
| Crystal system | Hexagonal |
| Space group | P62 |
| Unit cell dimensions (Å) | a = 15.6124(6) α = β = 90° |
| b = 15.6124(6) | |
| c = 10.6318(6) γ = 120° | |
| Unit-cell volume, V (Å3) | 2244.3(2) |
| Formula units per unit cell, Z | 6 |
| Calculated density, Dx (g cm–3) | 1.262 |
| Absorption coefficient, μ (mm–1) | 0.097 |
| F(000) | 912 |
| Crystal size (mm) | 0.56 (max) 0.04 (min) |
| Diffractometer | Siemens SMART CCD |
| Theta range for data collection (°) | 1.51—23.29 |
| Index ranges | –17 ≤ h ≤ 17, -17 ≤ k ≤ 15, -11 ≤ l ≤ 11 |
| Reflections collected | 8776 |
| Independent reflections [I > 2σ(I)] | 2141 (Rint = 0.044) |
| Refinement method | Full-matrix least-squares on F2 |
| Data / parameters | 2141 / 206 |
| Goodness of fit (all) | 1.013 |
| Final R indices [I > 2σ(I)] | R1 = 0.0490, wR2 = 0.1232 |
| R indices (all data) | R1 = 0.0706, wR2 = 0.1443 |
| Largest diff. peak and hole | 0.133 and –0.169 (e Å–3) |
a Standard deviations in parentheses.
| C4–C11 | 1.495(7) | C4–N1 | 1.449(5) |
| C4–C3 | 1.540(5) | C4–C5 | 1.546(5) |
| C3–O3 | 1.414(5) | C3–C2 | 1.525(6) |
| C2–O2 | 1.422(5) | C2–C1 | 1.512(6) |
| C1–O1 | 1.377(5) | C1–O5 | 1.429(5) |
| O5–C5 | 1.412(5) | C5–C6 | 1.507(6) |
| O3–C7 | 1.428(5) | O2–C7 | 1.439(5) |
| C7–C8 | 1.494(7) | C7–C9 | 1.509(6) |
| O1–C10 | 1.449(6) | C11–N2 | 1.133(6) |
| N1–C12 | 1.334(5) | O4–C12 | 1.238(5) |
| C12–C13 | 1.490(6) | C11–C4–N1 | 110.9(3) |
| C11–C4–C3 | 107.2(3) | N1–C4–C3 | 111.9(3) |
| C11–C4–C5 | 107.9(3) | N1–C4–C5 | 109.5(3) |
| C3–C4–C5 | 109.3(3) | O3–C3–C2 | 102.0(3) |
| O3–C3–C4 | 108.3(3) | C2–C3–C4 | 115.7(3) |
| O2–C2–C1 | 110.8(3) | O2–C2–C3 | 102.5(3) |
| C1–C2–C3 | 114.1(3) | O1–C1–O5 | 108.0(3) |
| O1–C1–C2 | 108.4(3) | O5–C1–C2 | 111.5(3) |
| C5–O5–C1 | 111.9(3) | O5–C5–C4 | 107.5(3) |
| O5–C5–C6 | 107.9(3) | C4–C5–C6 | 114.5(4) |
| C3–O3–C7 | 106.2(3) | C7–O2–C2 | 108.7(3) |
| O2–C7–O3 | 105.8(3) | O2–C7–C8 | 110.2(4) |
| O3–C7–C8 | 108.6(4) | O2–C7–C9 | 108.5(4) |
| O3–C7–C9 | 110.4(4) | C8–C7–C9 | 113.1(4) |
| C1–O1–C10 | 113.7(4) | N2–C11–C4 | 176.5(5) |
| C12–N1–C4 | 124.7(3) | O4–C12–N1 | 120.7(4) |
| O4–C12–C13 | 121.8(4) | N1–C12–C13 | 117.4(4) |
a Standard deviations in parentheses.
| C1–C2 – C3–C4 | –32.8(5) |
| H1–C1–C2–H2 | 156.2(5) |
| H2–C2–C3–H3 | –35.0(7) |
| C3–C4 – C5–O5 | –57.9(4) |
| C3–C2 – O2–C7 | 20.3(5) |
| C3–C4 – C5–C6 | –177.8(4) |
| O1–C1 – C2–O2 | –84.7(4) |
| C10–O1 – C1–O5 | –64.5(5) |
| C10–O1 – C1–C2 | 174.5(4) |
| C13–C12 – N1–C4 | –178.9(4) |
| O4–C12 – N1–C4 | 3.2(7) |
| O2–C2 – C3–O3 | –35.5(5) |
| O3–C3 – C4–C11 | 170.0(3) |
a Standard deviations in parentheses.
Table 4.
Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2 x 103) for compound 5a.
| Atom | x | y | z | U(eq) |
|---|---|---|---|---|
| C4 | 2055(3) | 4584(3) | 2104(4) | 40.0(9) |
| C3 | 1000(3) | 3989(3) | 1565(4) | 41.3(9) |
| H3 | 584(3) | 4240(3) | 1904(4) | 32(9) |
| C2 | 492(3) | 2871(3) | 1736(4) | 49.9(11) |
| H2 | 119(3) | 2682(3) | 2527(4) | 61(12) |
| C1 | 1188(3) | 2462(3) | 1702(4) | 49.8(10) |
| H1 | 1345(3) | 2398(3) | 826(4) | 35(9) |
| O5 | 2080(2) | 3080(2) | 2375(2) | 50.3(8) |
| C5 | 2622(3) | 4029(3) | 1829(4) | 45.5(10) |
| H5 | 2653(3) | 3957(3) | 917(4) | 63(13) |
| O3 | 1058(2) | 4084(2) | 241(3) | 46.9(7) |
| O2 | –175(2) | 2514(2) | 702(3) | 64.1(9) |
| C7 | 159(3) | 3280(3) | –236(4) | 52.6(11) |
| C9 | –614(4) | 3583(4) | –382(6) | 77(2) |
| H9A | –391(10) | 4110(16) | –985(21) | 105(23) |
| H9B | –721(16) | 3805(21) | 414(8) | 69(15) |
| H9C | –1221(7) | 3028(7) | –669(28) | 64(13) |
| C8 | 381(4) | 2933(4) | –1438(5) | 70.7(14) |
| H8A | 671(19) | 3471(7) | –2026(10) | 71(15) |
| H8B | –220(5) | 2405(14) | –1783(14) | 74(14) |
| H8C | 835(15) | 2700(18) | –1277(6) | 89(19) |
| O1 | 727(2) | 1546(2) | 2267(3) | 67.8(9) |
| C10 | 1284(4) | 1034(4) | 2189(6) | 81(2) |
| H10A | 892(12) | 374(11) | 2512(35) | 131(25) |
| H10B | 1879(15) | 1383(17) | 2676(30) | 113(24) |
| H10C | 1451(25) | 1004(26) | 1327(7) | 120(24) |
| C6 | 3657(3) | 4519(4) | 2355(5) | 63.7(13) |
| H6A | 4039(7) | 5170(9) | 2004(21) | 69(14) |
| H6B | 3960(8) | 4133(12) | 2143(24) | 74(14) |
| H6C | 3632(3) | 4566(19) | 3253(6) | 95(19) |
| C11 | 1959(3) | 4623(3) | 3498(5) | 46.1(10) |
| N2 | 1865(3) | 4602(3) | 4557(4) | 69.1(11) |
| N1 | 2592(2) | 5571(2) | 1576(3) | 40.1(8) |
| H4 | 3041(2) | 5687(2) | 1027(3) | 63(15) |
| O4 | 1834(2) | 6207(2) | 2705(3) | 57.6(8) |
| C12 | 2440(3) | 6313(3) | 1880(4) | 44.5(9) |
| C13 | 3050(4) | 7276(3) | 1223(5) | 63.2(13) |
| H13A | 2642(9) | 7384(19) | 644(37) | 184(42) |
| H13B | 3575(24) | 7261(15) | 772(41) | 138(27) |
| H13C | 3325(32) | 7801(5) | 1830(7) | 179(35) |
a Standard deviations in parentheses.
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MDPI and ACS Style
Koóš, M.; Steiner, B.; Gajdoš, J.; Langer, V.; Gyepesová, D.; Smrčok, L.; Ďurík, M. Crystal Structure of Methyl 4-Acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-ß-D-allopyranoside. Molecules 2000, 5, 219-226. https://doi.org/10.3390/50300219
AMA Style
Koóš M, Steiner B, Gajdoš J, Langer V, Gyepesová D, Smrčok L, Ďurík M. Crystal Structure of Methyl 4-Acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-ß-D-allopyranoside. Molecules. 2000; 5(3):219-226. https://doi.org/10.3390/50300219
Chicago/Turabian StyleKoóš, Miroslav, Bohumil Steiner, Ján Gajdoš, Vratislav Langer, Dalma Gyepesová, L'ubomìr Smrčok, and Marián Ďurík. 2000. "Crystal Structure of Methyl 4-Acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-ß-D-allopyranoside" Molecules 5, no. 3: 219-226. https://doi.org/10.3390/50300219
APA StyleKoóš, M., Steiner, B., Gajdoš, J., Langer, V., Gyepesová, D., Smrčok, L., & Ďurík, M. (2000). Crystal Structure of Methyl 4-Acetamido-4-cyano-4,6-dideoxy-2,3-O-isopropylidene-ß-D-allopyranoside. Molecules, 5(3), 219-226. https://doi.org/10.3390/50300219
