Application of Acyzol in the Context of Zinc Deficiency and Perspectives.

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.

Arabinogalactan propargyl ethers in the A3-coupling reaction with aldehydes and secondary cyclic amines.

A family of novel pharmacologically prospective carbohydrate polymer aminomethylpropargyl derivatives has been synthesized by CuI-catalyzed A3-coupling reaction of arabinogalactan propargyl ethers with aldehydes and secondary amines in DMSO at 23-65 °Ð¡. The arabinogalactan derivatives bearing phenyl, pyridinе, and furan moieties in combination with piperidyne, pyrrolidyne, morpholine fragments are prepared in up to 95 % yield and 0.3-2.0 degree of substitution. Conversion of the propargyl groups of the starting arabinogalactan ethers reaches in most cases 80-100 %. The non-catalyzed aminoalkylation (96-100 °Ð¡, degree of substitution up to 1.1) of propargylated AG proceeds both at the ethynyl and hydroxy centers to afford mainly the products of C-substitution. Some of the synthesized compounds and their hydrochlorination products show the pronounced bacteriostatic activity with respect to Gram-negative microorganism.

Pd-catalyzed cross-coupling of arabinogalactan propargyl ethers with 5-bromosalicylic acid.

New salicylate derivatives of arabinogalactan have been synthesized in up to 90% yield by cross-coupling of propargyl ethers of arabinogalactan with 5-bromosalicylic acid salts. The reaction proceeds in the presence of the catalytic system Pd(PPh3)4/PPh3 with CuBr (CuI), and piperidine or 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU) as a base in DMSO at 70-95 °Ð¡. The propargyl groups of the starting arabinogalactan ethers are converted into propinylsalicylate ones with 35 and 50% conversion depending on the nature of the base used. Degree of arabinogalactan substitution with propynyl salicylate fragments reaches 1.0 and 0.7 in the reactions with piperidine and DBU, respectively. In the case of piperidine, along with the main process, intensive unprecedented (for Sonogashira reaction) hydroamination of propargyl groups is also observed, followed by hydrolysis of unstable enamines. The products have been characterized by IR, 1Н and 13С NMR, UV spectroscopy as well as elemental analysis and gel permeation chromatography. Salicylate derivatives of arabinogalactan show high activity in prolonging the activated partial thromboplastin time (APTT), whereas neither the arabinogalactan nor propargyl ethers of arabinogalactan nor salicylic acid salts have obvious effects.

Arabinogalactan propargyl ethers: Au-catalysed hydroamination by imidazols.

A method for the synthesis of pharmacologically prospective arabinogalactan (AG) imidazole- and benzimidazole derivatives in a yield of up to 97 % via Au(III)-catalyzed hydroamination of AG propargyl ethers has been developed. It is found that in the presence of 5 mol% HAuC14 and 10-fold excess imidazole relative to the propargyl groups, the hydroamination successfully competes with cross-linking processes to afford products soluble in DMSO and aqueous HC1 solutions (degree of substitution of imidazolylpropenyl fragments 0.5-1.8, yield 62-97 %). It is established that under the conditions of hydroamination Au(III) is reduced to give mainly Au(0) and minor amounts of Au(I), which are contained in AG imidazole derivatives as particles of 190-640 nm in size. Hydrochlorides of Au-containing AG imidazole derivatives show high bacteriostatic activity with respect to test gram-positive microorganisms and thus confirming their prospects as new AG-derived bioactive agents.

Cross-coupling of propargylated arabinogalactan with 2-bromothiophene.

Novel pharmacologically prospective derivatives of arabinogalactan (a polysaccharide from larch wood) containing acetylenic and thiophene moieties have been obtained in up to 90% yield by cross-coupling of propargylic ethers of arabinogalactan with 2-bromothiophene. The reaction proceeds in the presence of the catalytic system Pd(Ph3P)4/CuBr/LiBr and piperidine in DMSO at 80-85°Ð¡. An advantageous feature of the synthesis is that it requires 5-25 times lesser catalytic loading than in common Sonogashira protocols thus making the reaction particularly beneficial to synthesize pharmaceutically-oriented polysaccharides.

Modification of arabinogalactan propargyl ethers by triazolyl functions.

Polysaccharide arabinogalactan (AG) has been modified by triazolyl functions via the copper-catalyzed 1,3-dipolar addition of azides to propargyl ethers. A range of new AG triazolo derivatives bearing benzyl, 4-vinylbenzyl, 1-naphthylmethyl, (1-vinylimidazol-2-yl)methyl, (1-ethylimidazol-2-yl)methyl, (1-vinylbenzimidazol-2-yl)methyl, allyl, carboxymethyl (as Na-salt) substituents is prepared by "one-pot" approach from organic azides generated in situ and AG propargyl ethers. The latter (degree of substitution 2.0-2.2) are converted into 1,2,3-triazolo AGs in DMSO/water mixture in the presence of CuSO4·5H2O/sodium ascorbate/Et3N in 82-94% yields and with 60-100% conversion.

Propargylation of arabinogalactan with propargyl halides--a facile route to new functionalized biopolymers.

New arabinogalactan propargyl ethers with degree of substitution (DS) up to 2.8 have been obtained by propargylation of arabino-3,6-galactan (AG) with propargyl bromide (PB) in the two-phase system 30-60% КОН aqueous solution/toluene in the presence of triethylbenzylammonium chloride (TEBAС) or without catalyst (ambient temperature, 1-24 h) in 20-87% yields. The highest yields have been reached using TEBAС as phase-transfer catalyst, though the non-catalytic version proves to be also efficient (DS 2.8, 70% yield). The propargylation of AG is less effective in the systems MОН (M=Na, K)/DMSO. DS of propargyl AG reaches 1.8 (70% yield) when propargyl chloride is used as propargylating agent, while with PB under the same conditions DS value does not exceed 0.4-0.6, the yields being 44-65%. Under the action of t-BuOK/DMSO system, the AG propargyl ethers have been isomerized to the corresponding unstable allenyl ethers. AG propargyl ethers with DS 2.0 have been almost exhaustively metallated with Ag2O/NH3 system to give AG-Ag acetylides derivatives with Ag/C≡C ratio equaling 0.95.