Crystal structure of (8R,10R,14R,Z)-12-hydroxy-2-((6-methoxypyridin-2-yl)methylene)-4,4,8,10,14-pentamethyl-17-((R)-2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-3H-cyclopenta[a]phenanthren-3-one–water (2/1), C₃₇H₅₆NO_4.5

Source of material

(8R,10R,14R)-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 (100 mg, 0.22 mmol) and 6-methoxy-2-pyridinecarboxaldehyde (30.0 mg, 0.22 mmol) were dissolved in 1.4 mL methanol. After adding 0.72 mL of 25% NaOH aqueous solution, the reaction system was opalescent. The reaction system was stirred at room temperature for 5 h. The response endpoint was detected by thin layer chromatography (TLC). When the reaction was stopped, a moderate amount of water was added to the container and the mixture was extracted with ethyl acetate (twice). The combined organic phase was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, filtered, reduced pressure concentration, yellow solid is obtained. The crude product was purified by silica-gel thin layer chromatography (petroleum ether: ethyl acetate = 3/1, v/v). The single crystal of the target compound was obtained by recrystallization with ethyl acetate solution.

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) = 0.93 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. Almost the whole organic molecule shows a disorder, which limits the significance of all bond lengths and angles. The figure shows only one of the two overlayed models.

Comment

Ginseng is a traditional Chinese medicinal plant, which has been widely used for the treatment of heart failure [4, 5] and various tissue damages under cellular and environmental stress. Ginseng is effective in improving blood circulation and brain function, enhancing immune function, preventing diabetes, as well as having anti-cancer, anti-inflammatory [6, 7] and antibacterial properties. Ginsenosides are the major active components of ginseng responsible for pharmacological actions. Ginsenoside are divided into two groups according to their glycosidic structures: dammarane and oleanane. There are two types of dammaranes: protopanaxadiol (PD) type [8, 9] and protopanaxatriol type sharing a tetrahydrofuran ring and a dammarane skeleton. Moreover, the conformation of the compound will have a certain influence on the biological activity [10]. Our group has done a lot of research work on panaxadiol derivatives [11] and panaxatriol derivatives [12], and obtained molecular data based on crystal structures [13, 14]. The title compound is a PD derivative. It is possible to modify the structure of ginsenoside which is an important saponin in ginsenoside.

Single-crystal structure analysis reveals that the title compound contains one drug molecule and one half of a water molecule in the asymmetric unit (cf. the Figure). Except for the substituents on C(2), the structure of the title compound is the same as that of panaxadiol. In the crystal structure, the pyridine ring has a planar conformation, and the other six membered rings except the ring with the keto group which has a chair conformation. The bond lengths and angles are all in the expected ranges.