DD205687A1 - PROCESS FOR PREPARING 1-0-ALKYL-3-0- (2,2,2-TRIFLUORETHYL) -GLYCERO-2-PHOSPHOCHOLINES - Google Patents

Abstract

THE INVENTION HAS THE OBJECT OF DEVELOPING A SUITABLE TECHNICAL APPLICABLE METHOD FOR PRODUCING THE FORMULA COMPOUNDS. The invention is directed to 1-0-ALKYL-3-0- (2,2,2-TRIFLUORETHYL) -GLYCERO-2-PHOSPHORIC ACID SS HALOGENAL CYLTERS WITH TRIMETHYLAMINE AT TEMPERATURES OF 40 TO 90 DEGREE CELSIUS 10 to 80 HOURS IN THE PRESENCE OF AN INNER SOLVENT HOW CHLOROFORM, ACETONITRILE AND ISO PROPANOL WERE IMPLEMENTED. THE QUARTAKY AMMONIUM HALOGENIDES PRODUCED ARE CONNECTED TO THE COMPOUNDS & IN ACCORDANCE WITH KNOWN METHODS. FORMULA &

Description

Dr. H. Brachwitz

Prof. Dr. P. long

Schildt

Dr. E. Hintsohe

"Process for the preparation of 1-O-alkyl-3-O- (2,2,2-trifluoroethiol ) -glomoero-2-pho3phocioliols"

Field of application of the invention

The invention relates to a process for the preparation of the 1-0-alkyl 1-3-0- (2,2,2-trifluoroethyl) -glyoero-2-phosphooholines of general formula I,

0H ₀ -OE

I ² ? «CH-OPO (OH,), - H (CH,),

I ö (-) ^{2Z 3 3}

CHOCHCS

in which E represents a long-chain saturated or unsaturated hydrocarbon residue with at least 8 carbon atoms, which may also be substituted калл. The compounds are closely related structurally to lecithin derivatives, which are found in numerous organisms and are of particular importance in biological processes. Field of application of the invention is the pharmaceutical or chemical industry.

Characteristics of the known technical solutions 1-O -alkyl-3-0- (2,2,2-trifluoroethyl) -glycero-2-phosphooholines of general formula I have not yet been described in the literature. It is only known that halogen-free O-acyl and di-O-alkyl-glycero-phosphocholines were synthesized by reacting O-acyl or di-O-alkyl glycero-phosphoric acid bromoethyl esters with trimethylamine

HIET and E. BEEOHTHOLD, Pharmacia Aota Helvetiae 22, 349 (1958), H. EIBL, D. ASHOLD, H.U. WELTZIHI, and 0. WBSTPHAL, Lisblegs Ann. Chem. 109, 226 (1967). ).

Aim of the invention

The object of the invention is to develop a suitable, technically applicable process for the preparation of 1-O-alkyl-3-0- (2,2,2-trifluoroethyl) -glycero-2-phosphocholines of general formula 1 га.

Presentation of the invention

The process according to the invention comprises reacting the 1-0-alkyl-3-0- (2,2,2-trifluoroethyl) -glycero-2-phosphoric acid-β-haloalkyl esters of the general formula II

CH ₀ -OE j * 0 СН-О -!> - О (сн ν-Σ И

I ОН CH ₂ -O-OH ₂ -CF ₃

in which E has the abovementioned meaning and X is Cl, 3r, J, is reacted with trimethylamine and the resulting quaternary ammonium halides are converted into the 1-0-alkyl-3-0- (2,2,2-trifluoroethyl) glycero 2-phosphocholines of general formula I, in which E has the meaning already mentioned, converted. The reaction of compound II is generally carried out with excess trimethylamine at temperatures between 40 and 90 ⁰ O over a reaction time between 10 and 48 Stands in the presence of inert solvents, preferably chloroform, acetonitrile and iso-propanol. The conversion of the first formed by the replacement of the halogen Σ in II quaternary ammonium halides in the compounds of type I is carried out according to known methods, for. By ion exchange or by treatment of II with silver acetate.

The compounds of the invention are biologically very active. For example, they inhibit the growth of Ehrlich-Ascitea-Tomor cells in vitro already Ъеі very low concentrations

 The invention will be illustrated by the following example.

Aasführangabe! Game

1-O-Hezadecyl-3-0- (2,2,2-trifluoroethyl) -glycero ^ -phosphocholine

(1, H = C ₁₆ H ₃₃ )

0.6 g (0.98 mmol) of 1-0-hexadecyl-3-0- (2,2,2-trifluoroethyl) glycero-2-phosphoric acid β-bromoethyl ester ClI, H "C-gH". Z = Br) are dissolved in 4.4 ml of chloroform. Bach addition of 7.3 ml of IBO-propanol, 7.3 ml of acetonitrile and 13.8 al 33% aqueous IrimethylaminlSsung the reaction mixture 24 is warmed to 50 ⁰ C heated. Thereafter, the solvent is concentrated and the residue is purified by column chromatography (100 g of Mallinchrodt silica gel, 100 mesh, eluent: chloroform / methanol / Аштопіак (25% aqueous bBsong), 65: 25: 3 v / τ / τ). From fractions 42 to 98 ( 8 ml each ) were added 0.43 g (73.2 % of theory ) of 1-0-hexadecyl-3-O- (2,2,2-trifluorotinyl) -glycero-2-one. phosphocholine (colorless crystals). F. 169-170 ° C (chloroform or acetone). Elemental Analysis: C ₂₆ H ₅₃ J ₃ HOgP (563.7)

Ber. C 53.69 H 9.53 1 2.41 Gef. C 53.35 H 9.44 H 2.39

Claims (1)

ErfindnngaaaBnrach Process aar Preparation of 1-0-alkyl-3-Q- (2,2,2-trifluoroethyl) -glycero-2-phosphocholines of general formula I, CH ₅ -OB IJ · θΗ-ο-ρ-ο (σΗ ₂ ) ₂ -Η (ΗΗ ₃ ) ₃ χ CH ₂ -O-CH ₂ -OK, in which R denotes a long-chain saturated or unsaturated hydrocarbon radical bit of at least 8 C atoms, characterized in that 1-0-Α1] 2 2 Ί-3-0- (2,2,2-ΐκΙί1αοΓ-ethyl) - glycero-2-phosphoric acid S-haloalkyl esters of general formula II, CH ₅ -OE
f S? CH-OPO (CHj) ₂ -X II in which R has the abovementioned meaning and X = Cl, Br, J, tri methylamine at temperatures of 40 to 70 ⁰ C, 10 to 48 hours in the presence of an inert solvent, preferably chloroform, acetonitrile and iso-propanol шпт and converting the resulting qaartären ammonium halides in the compounds I.