The coupling reagent PyBOP is widely used for the synthesis of different peptides and their amides, particularly for carboxamides of glycopeptide antibiotics of vancomycin or teicoplanin groups. The amidation reaction of the peptide core of the glycopeptide antibiotic eremomycin (I) with highly reactive amines in the presence of PyBOP is usually not accompanied by the formation of side products. However, the amidation of I with bulky amines (e.g., decyl amine and adamantyl amine) in the presence of PyBOP and Et3N or di-(i-Pr)2EtN (pH - 8.5) yielded N-unsubstituted carboxamide of eremomycin (Ia) as an admixture. The reaction of (I) or vancomycin (II) with an excess of PyBOP and Et3N (pH - 8.5) without addition of an amine or ammonia gave a mixture of products which contained higher amounts of the corresponding N-unsubstituted carboxamides (-20%). The structures of the samples of Ia and vancomycin amide (IIa) were proved by 1H NMR and ESI MS methods and confirmed by comparing with the authentic samples.

The synthesis of bis(indol-1-yl)maleimides and polycondenced diazepines[1,4], which contain various functional groups and are the analogs of biologically active indolo[2,3-а]carbazoles, is described. Functional groups were introduced directly into diazepine and bis-indolylmaleimide molecules via eletrophilic substitution reactions using precursors containing such functional groups.

The main achievements in the development of methods for the design of semisynthetic antibiotics of a new generation belonging to the group of polycyclic glycopeptides directed against infections caused by multidrug-resistant bacteria and dangerous human and animal viruses are reviewed. The review is focused on the results obtained at the Gauze Institute in the area of chemical modification of natural antibiotics (eremomycin, vancomycin, teicoplanin, etc.) directed toward modification of their antibacterial and/or antiviral activity. A special emphasis is placed on the study of the mechanisms of action of these antibiotics, which could be the basis of a rational approach to their chemical modification involving the transformation of the inner binding pocket and the peripheral regions of the molecules that participate in the formation of their complexes with targets. The study of the recently discovered antiviral activity of modified glycopeptide antibiotics is also discussed. A possibility of obtaining new highly active anti-HIV-1 and anti-HIV-2 preparations on the basis of hydrophobic derivatives of the aglycones of glycopeptide antibiotics was demonstrated. New semisynthetic derivatives of antibiotics that exhibit a high antibacterial activity in vivo, have good pharmacological characteristics, and are promising for practical use are described.

Ascorbigen, a natural product, is an indole derivative of L-ascorbic acid. Its effect on postnatal development and antibacterial resistance of the small intestine was studied on newborn mice. Ascorbigen was administered to 3-5-day old mice in a dose of 100 mg/kg orally every day for 7-10 days. 30 minutes before the last administration of the drug clinical isolates of Staphylococcus aureus or Escherichia coli were administered intragastrically to the young mice. The animals were killed in 24 hours and the frequency of the isolation of the microbes from the blood, spleen, kidneys and liver was developed. The oral use of the drug normalized the intestinal microflora, provided a reliable decrease of the bacteria isolation from the blood, spleen, kidneys and liver and prevented the animal death. The morphological examination showed that ascorbigen significantly increased the number and activity of the Paneth cells in the gland crypts, the goblet cells in the villi and mononuclear cells in the selfplate of the intestine mucous membrane vs. the intact control.

The influence of ascorbigen (ASG), which is a component of cruciferous vegetables, on the mucous tunic of small intestine and immune system organs in normal mice and mice, received cyclophosphamide (Cy), was evaluated by morphological examination. A significant increase of number of Paneth cells in the crypts and goblet cells in the villi was found in mice, received ASG per os in daily dose of 100 mg/kg for 14 days. The amount of eosinophylic granules in Paneth cells and their sizes also sharply increased. Germinative centers arose in lymphoid follicles of lymph nodes. ASG accelerated the processes of the damage reparation of a small intestine mucous tunic, caused by the single dose of 200 mg/kg Cy intraperitoneally. ASG administration after Cy as well as before it prevented atrophy of lymphoid tissue in lymphoid organs.