Affordances biology

Hydroxybenzofuran-5-carbaldehydes 682 can react with carbethoxymethylenetriphenyl-phosphorane 683 to afford biologically active furanocoumarins 684 in high yield. The reaction proceeds via Wittig reaction of the phosphorane 683 with the aromatic aldehyde to form the intermediate cinnamate, which then undergoes isomerization of the double bond and lactonization to furnish the desired furanocoumarins 684 (Scheme 165) <1995T3087>. 

As with the three polymeric examples, bipyridine ligands have been incorporated into polypeptides at the chain end, in the backbone, and as attached substituents. Specifically, a bipyridine has been coupled to either the amino or acid terminus of polypeptides to afford biological macroligands. For example, the 4,4 -dicarboxylic acid bipyridine was coupled to two 14-unit o-helices in order to analyze the conformation of the parallel structures.272 A triple-helical synthetic metallo-protein was formed through metal-templated self-assembly of a bipyridine unit with a 15-residue peptide substituted in the presence of metal ions.273... 

The hypervalent iodine-induced direct intramolecular cyclization of a-(aryl)alkyl-p-dicarbonyl derivatives 305 affords biologically important spirobenzannulated compounds 306 (Scheme 3.125) [366]. 

The Pictet-Spengler reaction is an important reaction involving condensation of an unsubstituted or substituted tryptamine 145 with an aldehyde RiCHO, usually in the presence of a Bronsted acid to afford an iminium ion 146 which undergoes intramolecular cyclization to afford biologically important tetrahydro- 3-carboline (147). Although the cyclization affords the C-2 adduct, the initial F-C product is the spirocyclic C-3 adduct, which... 

With a range of alkyl- and arylamines, various epoxides were successfully ring-opened using very low loadings of Al(OTf)3 (eq 10). Simple extraction of the catalyst into water made it reusable for the reaction up to three times without a decrease in efficiency.The solvent-free aminolysis of various epoxides by 2-picolylamine has been achieved with Al(OTf)3 as a key step for the synthesis of ionic liquids. Piperazines successfully opened terminal epoxides using Al(OTf)3 through SN2-type mechanism on the less hindered carbon atom to afford biologically active /3-amino alcohols derivatives. ... 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

Bl) The metrics effect is very significant in special theoretical examples, like a freely joined chain. In simulations of polymer solutions of alkanes, however, it only slightly affects the static ensemble properties even at high temperatures [21]. Its possible role in common biological applications of MD has not yet been studied. With the recently developed fast recursive algorithms for computing the metric tensor [22], such corrections became affordable, and comparative calculations will probably appear in the near future. 

There is a voluminous literature on the subject of amoebicidal agents, which is summarised up to 1932 by Fischl and Schlossberger. Recent work includes the clinical comparison by Manson-Bahr of a number of possible substitutes for emetine, the introduction of improved methods for the biological testing of potential amoebicides of which the papers by Jones and by Goodwin, Hoare and Sharp afford examples, and work... 

The oxygen atom in these molecules can in many cases be dispensed with as well substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. Friedel-Crafts acylation of the n-butyl ether of thiophenol with benzoyl chloride gives the corresponding benzophenone. Reduction of the ketone (15) followed by... 

Performance of an imaginary 1,2-shift on the benzhydrol antihistamines, that is, attachment of the side chain directly to the benzhydryl carbon while leaving the hydroxyl group intact, affords a series of molecules with markedly altered biologic activities. 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

Replacement of one of the phenyl groups by an alkyl group of similar bulk, on the other hand, alters the biologic activity in this series. Alkylation of phenylacetonitrile with isopropyl bromide affords the substituted nitrile, 136. Treatment of the anion prepared from 136 with strong base with 2-dimethylamino-l-chloropropane gives isoaminile (137). It is of note that alkylation of this halide, isomeric with that used in the early methadone synthesis, is apparently unaccompanied by isomer formation. Isoaminile is an agent with antitussive activity. 

Acylation of a sulfonamide on the amide nitrogen serves to remove the sometimes objectionable taste of these drugs. Reac-I ion of intermediate, 154, with acetic anhydride followed by reduction of the nitro group affords acetyl methoxyprazine (156). The last, which has much the same biologic action as Mie parent compound, is used for oral administration in syrups. 

A heterocyclic ring may be used in place of one of the benzene rings without loss of biologic activity. The first step in the synthesis of such an agent starts by Friedel-Crafts-like acylation rather than displacement. Thus, reaction of sulfenyl chloride, 222, with 2-aminothiazole (223) in the presence of acetic anhydride affords the sulfide, 224. The amine is then protected as the amide (225). Oxidation with hydrogen peroxide leads to the corresponding sulfone (226) hydrolysis followed by reduction of the nitro group then affords thiazosulfone (227). ... 

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