Racemic and optically active tocopherol analogues with a modified side chain: Synthesis and biological activity (Review)

Abstract

Information on the synthesis and biological activity of natural and synthetic analogues of alpha-tocopherol with a modified side chain is systematized. These compounds are of interest as vitamin E metabolites, hydrophilic antioxidants, and precursors of drugs with combined pharmacological properties useful in therapy of pathological disorders caused by oxidative stress.

Synthesis of conjugates of lupane triterpenoids with chromane antioxidants and in vitro study of their influence on the production of nitrogen monoxide and on the arginase activity in activated macrophages

“…Hybrid compounds with a trimethylated chro mane fragment that showed themselves as efficient poly functional agents have been reported earlier. [18][19][20] In the present work, we obtained a number of acylates of betulin and betulinic and betulonic acids with pharma cologically significant analogs of α tocopherol and stud ied in vitro the influence of some of the hybrid compounds on the NO production stimulated by lipopolysaccharides (LPS) and on the activity of arginase in mouse peritoneal macrophages. We also estimated their cytotoxic effects on macrophages.…”

Enantioselective Total Synthesis of the Natural γ-Tocopherol Metabolite (S)-γ-CEHC [(S)-LLU-α]

“…initial liposoluble tocopherols. 8 They exhibit antiinflammatory and natriuretic action, being endogenous ligands. 9 Unlike other diuretics, γ-CEHC selectively promotes the excretion of sodium ions without affecting the potassium ions.…”

“…The study of racemic γ-CEHC ( 1 ) in vitro in various model oxidative reactions has shown that, by its high antioxidant properties, it is comparable with α-tocopherol, ascorbic acid, and Trolox, a cardioprotective short-chain tocopherol analogue . On the other hand, short-chain hydrophilic analogues of tocopherols, such as 1 , are water-soluble metabolites of Vitamin E possessing unique properties distinguishing them from the initial liposoluble tocopherols . They exhibit antiinflammatory and natriuretic action, being endogenous ligands .…”

Synthesis of triterpene acids conjugates with α-tocopherol synthetic analogs

“…Chromanylethanol (V) was obtained from trimethylhydroquinone and 4-methyl-5,6-dihydro-2H-pyran [23]. Hemisuccinate esters of alcohols IV and VI were synthesized by reactions of compounds III and V with excess succinic anhydride in the presence of catalytic quantity of SPIVAK et al R 1 = OH, R 2 = H, R 3 = OH (VII); R 1 + R 2 = O, R 3 = Cl (VIII); R 1 = OH, R 2 = H, R 3 = Cl (IX); R 1 = OAc, R 2 = H, R 3 = Cl (X); R 1 + R 2 = O (XIa, XId); R 1 = OH, R 2 = H (XIb); R 1 = OAc, R 2 = H (XIc); R = Bn (XIIa, XIIb), H (XIIc,XIId); n = 0 (IIa, XIa-XIc); 1 (XII a, XIIc), 2 (XIIb, XIId), 4 By reacting compounds IIa and IIb with chlorides of betulonic (VIII), betulinic (IX), and O-acetylbetulinic (X) acids [24] we synthesized conjugates XIa-XId with a bridge from the residues of hydrazine and tetramethylenediamine. The yields of "hybrids" after the purifi cation by column chromatography on SiO 2 attained 60-65%.…”

“…Nowadays great expectations are pinned on the creation of new drugs for prevention and treatment of these diseases from hybrid compounds where the pharmacophores of various biologically active substances are combined with fragment of any oxidant molecules [4][5][6]. Numerous studies show the promising application in these combinations of the natural lipophilic antioxidant α-tocopherol and its synthetic analogs [7][8][9][10][11][12][13][14].…”