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BY 4.0 license Open Access Published by De Gruyter (O) July 30, 2021

Crystal structure of (8R,10R,14R, Z)-2-((3–Fluoropyridin-4-yl) methylene)-12-hydroxy-4,4,8,10,14-pentamethyl-17-((R)-2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-3H-cyclopenta[a] phenanthren-3-one, C36H52FNO3

Mei Zhang, Qing-Guo Meng, Gui-Ge Hou, Sheng Jiang, Yong-Sheng Jin and Yue Gao

Abstract

C36H52FNO3, orthorhombic, P212121 (no. 19), a = 7.8016(7) Å, b = 13.1609(10) Å, c = 30.536(2) Å, V = 3135.3(4) Å3, Z = 4, R gt (F) = 0.0657, wR ref (F2) = 0.1435, T = 100 K.

CCDC no.: 2087492

The molecular structure is shown in the figure. Displacement ellipsoids are drawn at the 30% probability level. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.13 × 0.12 × 0.10 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.08 mm−1
Diffractometer, scan mode: SuperNova,
θmax, completeness: 25.0°, >99%
N(hkl)measured, N(hkl)unique, Rint: 14226, 5509, 0.095
Criterion for Iobs, N(hkl)gt: Iobs > 2 σ(Iobs), 3824
N(param)refined: 379
Programs: CrysAlisPRO [1], SHELX [2], [3], [4]

Table 2:

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

Atom x y z Uiso*/Ueq
C1 0.2876 (6) 0.7168 (3) 0.60218 (14) 0.0267 (11)
H1A 0.391895 0.711210 0.585065 0.032*
H1B 0.201292 0.674928 0.588127 0.032*
C2 0.2280 (6) 0.8262 (3) 0.60106 (14) 0.0271 (11)
C3 0.1648 (6) 0.8737 (3) 0.64248 (15) 0.0270 (11)
C4 0.1101 (6) 0.8075 (3) 0.68105 (13) 0.0245 (11)
C5 0.1568 (6) 0.6943 (3) 0.67499 (13) 0.0241 (10)
H5 0.063715 0.666078 0.657200 0.029*
C6 0.1523 (7) 0.6339 (4) 0.71757 (15) 0.0344 (12)
H6A 0.247982 0.654206 0.735862 0.041*
H6B 0.047317 0.649423 0.733223 0.041*
C7 0.1616 (7) 0.5208 (4) 0.70934 (15) 0.0367 (13)
H7A 0.061956 0.500185 0.692562 0.044*
H7B 0.157977 0.485487 0.737197 0.044*
C8 0.3249 (6) 0.4888 (3) 0.68446 (14) 0.0275 (11)
C9 0.3439 (6) 0.5559 (3) 0.64300 (14) 0.0237 (10)
H9 0.248135 0.535487 0.624201 0.028*
C10 0.3222 (6) 0.6738 (3) 0.64821 (14) 0.0234 (10)
C11 0.5050 (6) 0.5247 (3) 0.61719 (17) 0.0342 (12)
H11A 0.512165 0.565863 0.590916 0.041*
H11B 0.605323 0.539177 0.634859 0.041*
C12 0.5085 (7) 0.4125 (4) 0.60404 (16) 0.0360 (13)
H12 0.420024 0.400024 0.581915 0.043*
C13 0.4765 (6) 0.3444 (3) 0.64334 (15) 0.0272 (11)
H13 0.572895 0.354512 0.663464 0.033*
C14 0.3121 (6) 0.3757 (3) 0.66842 (14) 0.0262 (11)
C15 0.3062 (8) 0.2928 (4) 0.70371 (16) 0.0412 (14)
H15A 0.381189 0.309854 0.727964 0.049*
H15B 0.190522 0.284310 0.714747 0.049*
C16 0.3676 (6) 0.1958 (4) 0.68072 (15) 0.0355 (13)
H16A 0.271161 0.151548 0.674560 0.043*
H16B 0.447942 0.159411 0.699215 0.043*
C17 0.4566 (6) 0.2288 (3) 0.63713 (14) 0.0248 (11)
H17 0.373820 0.218237 0.613419 0.030*
C18 0.4772 (7) 0.5014 (4) 0.71648 (16) 0.0406 (14)
H18A 0.484252 0.570963 0.725801 0.061*
H18B 0.581699 0.482664 0.701979 0.061*
H18C 0.460133 0.458459 0.741503 0.061*
C19 0.4816 (6) 0.7281 (4) 0.66655 (17) 0.0336 (12)
H19A 0.581300 0.706522 0.650655 0.050*
H19B 0.494925 0.711423 0.696960 0.050*
H19C 0.467863 0.800246 0.663459 0.050*
C20 0.6169 (6) 0.1648 (3) 0.62624 (14) 0.0259 (11)
C21 0.7709 (6) 0.1363 (3) 0.55358 (14) 0.0278 (11)
C22 0.7212 (7) 0.0240 (3) 0.55536 (15) 0.0334 (12)
H22A 0.614124 0.014163 0.539798 0.040*
H22B 0.808645 −0.015991 0.540749 0.040*
C23 0.7014 (7) −0.0131 (3) 0.60216 (17) 0.0370 (13)
H23A 0.664489 −0.083511 0.602121 0.044*
H23B 0.810835 −0.009248 0.617123 0.044*
C24 0.5703 (6) 0.0516 (3) 0.62608 (16) 0.0314 (12)
H24A 0.560877 0.027979 0.656078 0.038*
H24B 0.459356 0.042988 0.612253 0.038*
C25 0.7660 (6) 0.1871 (4) 0.65689 (15) 0.0360 (13)
H25A 0.852674 0.136031 0.653322 0.054*
H25B 0.726081 0.186868 0.686630 0.054*
H25C 0.813223 0.252583 0.650055 0.054*
C26 0.7344 (7) 0.1796 (4) 0.50828 (15) 0.0427 (14)
H26A 0.614838 0.171870 0.501664 0.064*
H26B 0.801332 0.143779 0.486873 0.064*
H26C 0.764126 0.250339 0.507754 0.064*
C27 0.9583 (6) 0.1531 (4) 0.56523 (16) 0.0371 (13)
H27A 0.981809 0.224626 0.566207 0.056*
H27B 1.029718 0.121637 0.543501 0.056*
H27C 0.981740 0.123517 0.593348 0.056*
C28 0.1773 (7) 0.8549 (4) 0.72367 (15) 0.0385 (13)
H28A 0.299030 0.844937 0.725551 0.058*
H28B 0.122654 0.822938 0.748248 0.058*
H28C 0.152381 0.926278 0.723871 0.058*
C29 −0.0879 (6) 0.8160 (4) 0.68132 (15) 0.0298 (11)
H29A −0.120492 0.884406 0.688456 0.045*
H29B −0.134178 0.770291 0.702755 0.045*
H29C −0.131715 0.798728 0.652905 0.045*
C30 0.1515 (6) 0.3583 (4) 0.63932 (18) 0.0409 (13)
H30A 0.138679 0.287031 0.633559 0.061*
H30B 0.165081 0.394166 0.612156 0.061*
H30C 0.051609 0.383047 0.654253 0.061*
C31 0.2241 (6) 0.8849 (4) 0.56523 (16) 0.0308 (12)
H31 0.183236 0.950435 0.569761 0.037*
C32 0.2741 (6) 0.8621 (3) 0.52005 (14) 0.0264 (11)
C33 0.3199 (6) 0.9395 (3) 0.49219 (16) 0.0283 (11)
C34 0.3694 (6) 0.9244 (4) 0.44913 (16) 0.0331 (12)
H34 0.399698 0.980146 0.432114 0.040*
C35 0.3272 (8) 0.7547 (4) 0.45781 (16) 0.0429 (14)
H35 0.328042 0.689437 0.446141 0.051*
C36 0.2773 (7) 0.7658 (4) 0.50100 (16) 0.0366 (12)
H36 0.245824 0.709137 0.517320 0.044*
F1 0.3172 (4) 1.03671 (18) 0.50736 (9) 0.0384 (7)
N1 0.3748 (5) 0.8318 (3) 0.43148 (13) 0.0357 (10)
O1 0.1510 (4) 0.9668 (2) 0.64495 (11) 0.0365 (8)
O2 0.6732 (6) 0.3964 (3) 0.58506 (16) 0.0782 (16)
H2 0.692325 0.335271 0.583501 0.117*
O3 0.6564 (4) 0.1952 (2) 0.58156 (9) 0.0262 (7)

Source of material

The title compound was synthesized by three-step chemical reactions in turn. First, ginsenoside of stems and leaves (GSL) was degraded by 10% sulfuric acid ethanol solution and purified by silica gel column chromatography. After recrystallization in ethyl acetate and CH2Cl2, the pure white crystalline product panaxadiol (PD; systematic name: (3S, 5R,8R,9R,10R,12R,13R,14R,17S)-4,4,8,10,14-pentamethyl-17 -((R)-2,6,6-trimethyltetra-hydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta[a] phen-anthrene-3,12-diol)-was obtained. Second, panaxadiol and PCC were dissolved in 25 ml dichloromethane(methylene chloride) solution and stirred for 4 h at room temperature. The product 3-oxo-panaxadiol was purified by silica gel column chromatography. Finally, in a representative experiment 0.72 mL (25%) of sodium hydroxide aqueous solution was added dropwise to the mixture of 3-oxo-panaxadiol (100 mg; 0.218 mmol) and 3-fluoropyridine-4-formaldehyde (0.022 ml; 0.218 mmol) in 1.4 mL methanol and stirred at room temperature for 2.5 h. The in process-control was monitored by silica gel thin layer chromatography (TLC, 254 nm), the developing solvent is petroleum ether and ethyl acetate. When the reaction was finished, the reaction system was extracted twice with appropriate amount of water and ethyl acetate, and the third time with brine and ethyl acetate. The crude yellow oil was obtained by vacuum distillation of the organic phase and the title compound was purified by silica gel column chromatography. Suitable crystals of the title compound were obtained by recrystallization in ethyl acetate system and dried under vacuo at 65 °C for 5 h.

Experimental details

The H atoms were placed in idealized positions and treated as riding on their parent atoms, with d(C–H) = 0.97 Å (methylene), d(C–H) = 0.98 Å (aromatic), d(C–H) = 0.96 Å (methyl), d(C–H) = 0.93 Å (alkenyl) and d(O–H) = 0.82 Å (–OH). The absolute configuration was derived from the synthesis and the configuration of the educts.

Comment

Ginsenoside are divided into two groups according to their glycosidic structures: dammarane and oleanane. There are two types of dammaranes: protopanaxadiol type [5, 6] and protopanaxatriol type sharing a tetrahydrofuran ring and a dammarane skeleton. Because these ginsenosides and their derivatives have a wide range of biological activities, such as anticancer, enhancing myocardial function [7], anti-inflammatory [8] and analgesic, their synthesis and biological activities have attracted extensive attention. At the same time the conformation of the compound will have a certain influence on the biological activity [9]. Our laboratory has done a lot of research work on panaxadiol derivatives [10, 11] and panaxatriol derivatives [12], and obtained crystal structures [13] with good data. The title compound is a PD derivative. It is possible to modify the structure of ginsenoside which is an important saponin in ginsenoside [14].

Single crystal X-ray structure analysis of the title compound revealed that the substituents are at on C(2), the structure of the title compound is similar to that of panaxadiol. In the crystal structure, the pyridine ring is planar, and the other six membered rings except the ring with the keto group have chair conformation. The bond lengths and angles are all in the expected ranges [12].


Corresponding author: Yue Gao, Department of Lab Teaching, School of Pharmacy, Naval Medical University, Shanghai, 200433, P. R. China, E-mail:

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81473104, 81773563, 81573585

Funding source: Science Foundation

Award Identifier / Grant number: 13ZJZ06

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the National Natural Science Foundation of China (No. 81473104, 81773563). Meanwhile, this work was also supported by National Natural Science Foundation of China (Grant no. 81573585) and other Science Foundation (No. 13ZJZ06).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-06-17
Accepted: 2021-07-19
Published Online: 2021-07-30
Published in Print: 2021-12-20

© 2021 Mei Zhang et al., published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.