Synthesis of biologically active heterocycles by domino reactions with SN2/Thorpe-Ziegler reaction step.

Synthesis ◽  
2021 ◽  
Author(s):  
Natalia Larionova ◽  
Anatoliy Mikhaylovich Shestopalov ◽  
Lyudmila Aleksandrovna Rodinovskaya ◽  
Andrey Zubarev

The review includes methods for the synthesis of five- and six-membered heterocycles and their annulated analogs. These methods are based on anionic domino reactions, which have a common step - SN2/Thorpe-Ziegler reaction. Data on the biological activity of these heterocycles are summarized.

Synthesis ◽  
2021 ◽  
Author(s):  
Stefan H. Bossmann ◽  
Raul Neri

AbstractIsoselenocyanates (ISCs) are a class of organoselenium compounds that have been recognized as potential chemotherapeutic and chemopreventative agents against cancer(s) and infectious diseases. ISC compounds are chemically analogous to their isosteric relatives, isothiocyanates (ITCs); however, they possess increased biological activity, such as enhanced cytotoxicity against cancer cells. ISCs not only serve as significant products, but also as precursors and essential intermediates for a variety of organoselenium compounds, such as selenium-containing heterocycles, which are biologically active. While syntheses of ISCs have become less difficult to accomplish, the syntheses of selenium-containing heterocycles are often difficult due to the use of highly toxic selenium reagents. Because of this, ISCs can serve as versatile reagents for the preparation of these heterocycles. In this review, the classical and recent syntheses of ISCs will be discussed, along with notable and recent synthetic work employing ISCs to access novel selenium-containing heterocycles.1 Introduction1.1 Selenium and Health2 Isoselenocyanates2.1 Preparation of Isoselenocyanates3 Selenium-Containing Heterocycles3.1 Notable Synthetic Work3.2 Recent Synthetic Work3.2.1 Synthesis of N-(3-Methyl-4-phenyl-3H-selenazol-2-ylidene)benzamide­ Derivatives3.2.2 Synthesis and X-ray Studies of Diverse Selenourea Derivatives3.2.3 Synthesis of Heteroarene-Fused [1,2,4]Thiadiazoles/Selenadiazoles via Iodine-Promoted [3+2] Oxidative Cyclization3.2.4 2-Amino-1,3-selenazole Derivatives via Base-Promoted Multicomponent Reactions4 Conclusion


2011 ◽  
Vol 6 (11) ◽  
pp. 1934578X1100601
Author(s):  
Karsten Krohn ◽  
Stephan Cludius-Brandt ◽  
Barbara Schulz ◽  
Mambatta Sreelekha ◽  
Pottachola Mohamed Shafi

Several biologically active alkaloids (1-4, 6), including a new quinazoline-6-carboxylic acid (1), were isolated from the medicinal plant Zanthoxylum rhetsa, an evergreen tree, native to subtropical areas. Whereas the pharmacological properties of the plant extract and single constituents have been widely tested, we now show that all of the metabolites have antialgal activities, all but 6 are antibacterial, and 6 and the reduction product 5 (derived from 4) are also antifungal.


1988 ◽  
Vol 8 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
E Lazar ◽  
S Watanabe ◽  
S Dalton ◽  
M B Sporn

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.


1991 ◽  
Vol 11 (7) ◽  
pp. 3603-3612
Author(s):  
S Marcus ◽  
G A Caldwell ◽  
D Miller ◽  
C B Xue ◽  
F Naider ◽  
...  

We have undertaken total synthesis of the Saccharomyces cerevisiae a-factor (NH2-YIIKGVFWDPAC[S-farnesyl]-COOCH3) and several Cys-12 analogs to determine the significance of S-farnesylation and carboxy-terminal methyl esterification to the biological activity of this lipopeptide mating pheromone. Replacement of either the farnesyl group or the carboxy-terminal methyl ester by a hydrogen atom resulted in marked reduction but not total loss of bioactivity as measured by a variety of assays. Moreover, both the farnesyl and methyl ester groups could be replaced by other substituents to produce biologically active analogs. The bioactivity of a-factor decreased as the number of prenyl units on the cysteine sulfur decreased from three to one, and an a-factor analog having the S-farnesyl group replaced by an S-hexadecanyl group was more active than an S-methyl a-factor analog. Thus, with two types of modifications, a-factor activity increased as the S-alkyl group became bulkier and more hydrophobic. MATa cells having deletions of the a-factor structural genes (mfal1 mfa2 mutants) were capable of mating with either sst2 or wild-type MAT alpha cells in the presence of exogenous a-factor, indicating that it is not absolutely essential for MATa cells to actively produce a-factor in order to mate. Various a-factor analogs were found to partially restore mating to these strains as well, and their relative activities in the mating restoration assay were similar to their activities in the other assays used in this study. Mating was not restored by addition of exogenous a-factor to a cross of a wild-type MAT alpha strain and a MATaste6 mutant, indicating a role of the STE6 gene product in mating in addition to its secretion of a-factor.


1991 ◽  
Vol 11 (7) ◽  
pp. 3603-3612 ◽  
Author(s):  
S Marcus ◽  
G A Caldwell ◽  
D Miller ◽  
C B Xue ◽  
F Naider ◽  
...  

We have undertaken total synthesis of the Saccharomyces cerevisiae a-factor (NH2-YIIKGVFWDPAC[S-farnesyl]-COOCH3) and several Cys-12 analogs to determine the significance of S-farnesylation and carboxy-terminal methyl esterification to the biological activity of this lipopeptide mating pheromone. Replacement of either the farnesyl group or the carboxy-terminal methyl ester by a hydrogen atom resulted in marked reduction but not total loss of bioactivity as measured by a variety of assays. Moreover, both the farnesyl and methyl ester groups could be replaced by other substituents to produce biologically active analogs. The bioactivity of a-factor decreased as the number of prenyl units on the cysteine sulfur decreased from three to one, and an a-factor analog having the S-farnesyl group replaced by an S-hexadecanyl group was more active than an S-methyl a-factor analog. Thus, with two types of modifications, a-factor activity increased as the S-alkyl group became bulkier and more hydrophobic. MATa cells having deletions of the a-factor structural genes (mfal1 mfa2 mutants) were capable of mating with either sst2 or wild-type MAT alpha cells in the presence of exogenous a-factor, indicating that it is not absolutely essential for MATa cells to actively produce a-factor in order to mate. Various a-factor analogs were found to partially restore mating to these strains as well, and their relative activities in the mating restoration assay were similar to their activities in the other assays used in this study. Mating was not restored by addition of exogenous a-factor to a cross of a wild-type MAT alpha strain and a MATaste6 mutant, indicating a role of the STE6 gene product in mating in addition to its secretion of a-factor.


1948 ◽  
Vol 87 (5) ◽  
pp. 445-455 ◽  
Author(s):  
Walther F. Goebel ◽  
Peter K. Olitsky ◽  
Arturo C. Saenz

The action of periodic acid on two biologically active proteins, crystalline ribonuclease and pneumococcus Type III immune globulin, and on the virus of Western equine encephalomyelitis has been studied. The biological activity of the two proteins and the pathogenic action of the virus were destroyed by the reagent; the specific antigenicity of the immune globulin was retained, however, but that of the equine virus was lost. The bearing of these reactions on the chemical alteration of the respective substances has been discussed.


1951 ◽  
Vol 41 (3) ◽  
pp. 577-591 ◽  
Author(s):  
A. B. M. Whitnall ◽  
W. M. McHardy ◽  
G. B. Whitehead ◽  
F. Meerholz

“Gammexane” and DDT, have many advantages over arsenic as tick killing agents. “Gammexane” dips have been used successfully to control the one host arsenic-resistant blue tick, B. decoloratus (Koch) but these dips have not been fully investigated for the control of two- and three-host ticks. The control of the three-host bont tick, A. hebraeum, a vector of “heartwater”, a disease of cattle, sheep and goats, is of great economic importance to South Africa. Larvae and nymphs seem to occur on cattle to a lesser degree than adults, but each stage shows a definite preference for particular sites on the host. For this reason, control measures have to be mainly directed against the adult stage. The effect of “Gammexane”, DDT and arsenical dips, and combinations of these, has been investigated, by making weekly counts of adults on treated and untreated groups of animals. Dipping has been compared with spraying, and the results have been examined in the light of chemical analyses and biological tests with the same samples. The experiments were spread over two consecutive years.Preliminary experiments indicated that all treatments markedly reduced numbers of male bont ticks on the cattle. Weekly arsenical treatments with 0·16 per cent. As2O3 either by dipping or spraying did not reduce the numbers of females, nor did a composite dip-wash of 0·16 per cent. As2O3 and 50 p.p.m. gamma isomer. Dipping in 50 p.p.m. gamma isomer gave slightly better results against females than the above treatments. Encouraging results were obtained by spraying cattle with freshly diluted wash containing 50 p.p.m. gamma isomer, but dipping in 100 p.p.m. also gave satisfactory results. The relative ineffectiveness of dipping as compared with spraying, was found to be due to the loss of biological activity of hexachlorocyclohexane in dipping tanks, where complicating pollution factors appeared.The results of the preliminary experiments were largely confirmed by the second series. Males always outnumbered females in collections where the ticks were removed week by week from cattle. The collections were taken to represent the rate at which cattle became re-infested, and formed a basis on which to gauge the effectiveness of treatments. Males increased in numbers week by week on other untreated control groups of cattle, and eventually greatly outnumbered the females. This suggested that males remained on the hosts longer, and were recorded more than once in the consecutive weekly counts.All treatments reduced the numbers of males. Weekly treatments in 0·16 per cent. As2O3 did not reduce the numbers of females, nor did it prevent them from engorging. Some females laid after removal from cattle so treated but the eggs were sterile, whilst females in a similar state of engorgement, removed from untreated animals, laid fertile eggs. Arsenical treatments should thus eventually control bont ticks.All “Gammexane” treatments appeared more effective than the arsenical treatments. Fresh dilutions of dispersible pastes and powders in the form of sprays gave better results than dipping in the same preparations at comparable concentrations. This was due to a loss in biological activity of the hexachlorocyclohexane as the washes became dirty with use in dipping tanks. This factor makes chemical determinations of dip-washes, based on total hydrolysable chlorine, of little value, unless these data are correlated with some suitable biological test. The addition of 0·03 per cent, copper sulphate in the wash did not prevent the loss of biological activity.Oil emulsion dips, which were known to show a drop in the gamma isomer content with use in dipping tanks, were kept at the desired concentration and biologically active by adding fresh dip each week. In such cases both dip- and spray-washes gave satisfactory results when used at 100 p.p.m. gamma isomer. A combination of 50 p.p.m. gamma isomer and 0·16 per cent. As2O3 used as a dip-wash was not satisfactory in reducing the number of bont ticks, and little better than a fresh spray of 50 p.p.m. gamma isomer alone. The striking results given by a combination of a dispersible powder spray of 50 p.p.m. gamma isomer and 0·1 per cent. p,p′ DDT might be due to persistent action or repellent effect.Arsenic is a stable substance and has been used for many years in dipping tanks to control ticks. It has disadvantages and in the case of the bont tick many females remained attached to the hosts when treated weekly in arsenic, although the engorged females laid sterile eggs. “Gammexane” preparations when used at 100 p.p.m. gave satisfactory results. These preparations, however, lost their biological activity in dipping tanks, and the best results were obtained when they were applied to cattle as fresh sprays.


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