METHOD OF PRODUCING (2RS)-2,5,7,8-TETRAMETHYL-2-[(4RS,8RS)-4,8,12-TRIMETHYLTRIDECYL]-CHROMAN-6-YL-N-[3-OXOLUP-20(29)-EN-28-OYL]-GLYCINATE Russian patent published in 2012 - IPC C07J53/00 C07J63/00 

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of biologically active substances, specifically to synthesis of (2RS)-2,5,7,8-tetramethyl-2-[(4RS,8RS)-4,8,12-trimethyltridecyl]-chroman-6-yl-N-[3-oxolup-20(29)-en-28-oyl]-glycinate (1) - a hybrid molecule combined from d,l-α-tocopherol (vitamin E) (2) and betulinic acid (3) through a bridge constructed from a glycine residue. The combination of α-tocopherol and betulinic acid can lead to mutual synergetic effect of the combined molecules or appearance of a hybrid compound with new biological activity. The invention involves reaction of α-tocopherol (2) with N-(benzyloxycarbonyl) -glycine (CBz-Gly), activated N,N'-dicyclohexyl carbodiimide (DCC) and para(N,N'-dimethylamino) pyridine (DMAP) in methylene chloride at room temperature for 2 hours in molar ratio α-tocopherol: CBz-Gly:DCC:DMAP, equal to 1:(1-1.5):(1-1.5):0.15, with extraction of the product (5) through column chromatography on silica gel with output of 82% and subsequent unblocking of the amino group via hydrogenolysis over a palladium catalyst in ethanol with output of 88% of d,l-α-tocopherol-glycinate (6) and involvement thereof in coupling with acyl chloride of betulinic acid (4), obtained directly before action of oxalyl chloride on betulinic acid. The coupling reaction is carried out in dry benzene, chloroform or methylene chloride at room temperature or boiling (primarily while boiling) for 1 hour, molar ratio acyl chloride (4): glycinate (6) equal to 1:(1-1.5). The reaction product is separated using column chromatography on silica gel. Output of the hybrid (1) is equal to 67-79% in terms of acyl chloride (4).

EFFECT: high output of end product.

1 cl, 6 ex