PL228421B1 - 1'-[(3,7-Dimethyl-3-vinylocta-6-enyl)]-2'-hydroxy-sn-glycero-3'-phosphocholine and method for obtaining it - Google Patents

Description

The present invention relates to 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3'-phosphocholine of formula 1 as shown in the drawing.

The invention also relates to a method for the preparation of 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3'-phosphocholine of formula 1.

The invention may find application in the cosmetics and pharmaceutical industries as well as in the treatment of neoplastic diseases.

The aim of the invention was to develop a method for the preparation of a new lysophosphatidylcholine containing a 3,7-dimethyl-3-vinylocta-6-enoic acid molecule at the sn-1 position of phosphatidylcholine, which in this case acts as an active carrier; biologically isoprenoidic acid, facilitating its penetration into living cells.

From the application of the invention, P. 418652, a phosphatidylcholine is known containing two 3,7-dimethyl-3-vinylocta-6-enoic acid molecules simultaneously in the sn-1 and sn-2 positions of phosphatidylcholine. On the other hand, from the description of the invention P. 418945 there is known phosphatidylcholine containing a palmitic acid molecule in the sn-1 position and a 3,7-dimethyl-3-vinylocta-6-enoic acid molecule in the sn-2 position.

There is no known lysophosphatidylcholine containing 3,7-dimethyl-3-vinylocta-6-enoic acid only at the sn-1 position.

The essence of the invention is the 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3'-phosphocholine shown in the drawing and the method of its preparation.

The essence of the method of obtaining lysophosphatidylcholine with a molecule of 3,7-dimethyl-3-vinylocta-6-enoic acid is that a mixture of sn-glycero-3-phosphocholine (GPC) and dibutyltin oxide (DBTO) dissolved in anhydrous 2-propanol is subjected to reaction with 3,7-dimethyl-3-vinylocta-6-enoic acid chloride, also dissolved in propan-2-ol, in the presence of triethylamine (TEA). The mixture is stirred for at least 1 hour at the reflux temperature of the solvent, and then the resulting product is isolated and purified by column chromatography.

The method according to the invention is explained in more detail using an exemplary embodiment.

P r z k ł a d 1

To a round bottom flask containing 8 cm ^{3 of} 2-propanol was added 300 mg (1.16 mmol) of dried sn-glycero-3-phosphocholine (GPC) and 290 mg (1.17 mmol) of dibutyltin oxide (DBTO) and the mixture heated at the boiling point of the solvent for 1 hour. After this time, the reaction mixture is cooled and 242 mg (2.4 mmol) of triethylamine (TEA) and 515 mg (2.4 mmol) of 3,7-dimethyl-3-vinylocta-6-enoic acid chloride dissolved in 4 cm ^{3 are added.} anhydrous 2-propanol. The suspension is vigorously stirred at room temperature under N2 atmosphere for 1 hour. After this time, the reaction mixture was filtered under reduced pressure on a Schott funnel through a celite pad, and then the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using a solvent mixture of CHCl3: MeOH: H2O, 65: 25: 4 (v / v / v) as the eluent. 162 mg (0.37 mmol) of 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-3-glycero-3'-phosphocholine are obtained with a yield of 32% in greasy form of> 98% purity (by HPLC).

The spectroscopic data of the obtained compound are as follows;

¹ H NMR (600 MHz, CDCl / CDaOD 2: 1 (v / v)), 5: 0.91 (s, 6H, CHs-11 (A), the CH-11 (B)), 1.17-1.21 (m, 4H , CH2-4 (a), CH2-4 (B)), 1.35, 1.44 (two s, 12H, CH3-8 (A), CH3-8 (B), CH3-12 (A), CH3-12 ( B)), 1.68 (m, 4H, CH2-5 (A), CH2-5 (B)), 2.12-2.17 (two d, J = 13.8 Hz, 4H, AB system, CH2-2 (A) , CH2-2 (B)), 2.99 (s, 18H, -N (CH3) 3 (A), -N (CH3) 3 (B)), 3.38 (m, 4H, CH2-3 (A), CH2 -3 (B)), 3.63-3.66 (m, 2H, one of CH2-3 '(A), one of CH2-3' (B)), 3.66-3.73 (m, 4H, H-2 '(A ), H-2 '(B), one of CH2-3' (A), one of CH2-3 ') (B)), 3.83-3.91 (two m, 4H, CH2-1' (A), CH2 -1 '(B)), 4.01-4.06 (m broad, 4H, CH2-a (A), CH2-a (B)), 4.74 (d, J = 18.0 Hz, 2H, one of CH2-10 (A), one of CH2-10 (B)), 4.81 (d, J = 10.8 Hz, 2H, one of CH2-10 (A), one of CH2-10 (B)) 4.84 (t, J = 7.2 Hz, 2H, H-6 (A), H-6 (B)), 5.92 (dd, J = 18.0, 10.8 Hz, 2H, H-9 (A), H-9 (B)) ; ^{1 3} C NMR (151 MHz, CDCl 3 / CD 3 OD 2: 1 (v / v)) 5: 16.86, 24.93 (C-8 (A), C-8 (B), C-12 (A), C-12 (B)), 22.40 (C-11 (A), C-11 (B)), 22.43 (C-5 (A), C-5 (B)), 38.75 (C-3 (A), C- 3 (B)), 40.35, 40.38 (C-4 (A), C-4 (B)), 44.48, 44.50 (C-2 (a), C-2 (B)), 53.67 (t, J = 3.6 Hz, -N (CH3) 3 (A), -N (CH3) 3 (B)), 58.64 (d, J = 4.9 Hz, C-α (A), C-α (B)), 64.37 ( C-1 '(A), C-1' (B)), 66.09 (m, C-β (A), C-β (B)), 66.55 (d, J = 5.7 Hz,

PL 228 421 Β1

C-3 '(A), C-3' (B)), 68.36 (d, J = 6.5 Hz, C-2 '(A), C-2' (B)), 111.71 (C-10 (A), C-10 (B)), 123.93 (C-6 (A), C-6 (B)), 130.95 (C-7 (A), C-7 (B)), 144.94 (C- 9 (A), C-9 (B)), 171.75 (C-1 (A), C-1 (B));

³¹ P NMR (243 MHz, CDCl3 / CD3OD 2: 1 (ν / ν)) δ: -0.04;

(α, β) - indicates choline-derived signals

Claims (2)

1. 1 '- [(3,7-Dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3'-phosphocholine, Formula 1 shown in the drawing. Method for the preparation of 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3-phosphocholine, characterized in that the 3,7-dimethyl-3-acid chloride -vinylocta-6-ene is reacted with sn-glycero-3-phosphocholine and dibutyltin oxide in the presence of triethylamine, the reaction is carried out in anhydrous 2-propanol and the suspension is stirred for at least one hour, then the resulting 1 '- [(3,7-dimethyl-3-vinylocta-6-enyl] -2'-hydroxy-sn-glycero-3'-phosphocholine.