Structural analogues of the

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

New organocatalysts prepared by the Jacobsen group showed that alkylation of the final amide bond increased the enantioselection (Scheme 38, compare R2 = Me, 98% ee to R2 = H, 91% ee). Thus, the reaction performed with N-allyl benzaldimine and with the dimethylamide-ending thiourea (Scheme 38 with Ri = R2 = Me) gave up to 99% ee. This compound is a structural analogue of the urea depicted in Scheme 36 [148,152,154]. 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

The affinity of platinum(II) for N-donor ligands is well established. There are numerous examples in the literature of mono-, di-, and trinuclear platinum(II)-ammine and alkylamine complexes, most of which are structural analogues of the anticancer agent, mplatin (cis- PtCl2(NH3)2]), and the corresponding trans isomer. Selected novel complexes and synthetic methods are presented below. 

Hong and coworkers have investigated the cycloaddition chemistry of fulvenes with a wide variety of alkenes and alkynes in great detail [191]. As one example, the reaction of 6,6-dimethylfulvene with benzoquinone is shown in Scheme 6.92. Under microwave conditions in dimethyl sulfoxide (DMSO) at 120 °C, an unusual hetero-[2+3] adduct was formed in 60% yield, the structure of which was determined by X-ray crystallography. The adduct is a structural analogue of the natural products aplysin and pannellin and differs completely from the reported thermal (benzene, 80 °C) Diels-Alder cycloaddition product of the fulvene and benzoquinone (Scheme 6.92) [191]. 

Although hitherto no structural analogue of the complete heterodimetallic nickel-iron centre of [NiFe] hydrogenase has been reported, some compounds with similarities to the biological centre were recently synthesized using specially designed... 

As structural analogues of the phenothiazines, thioxanthenes (e.g., chlorprothixene, flupentixol) possess a central nucleus in which the N atom is replaced by a carbon linked via a double bond to the side chain. Unlike the phenothiazines, they display an added thy-moleptk activity. 

Tetradentate S N N S aminothiolato ligands found considerable interest since their complexes represent structural analogues of the neutral technetium(V) complex [TcO(ECD)] (H3ECD = A, A -l,2-ethylenediylbis-L-cysteine diethylester, (160) with R = = H,... 

A physiological mechanism of metabolic regulation via competitive inhibition by structural analogues of the substrate. 

And finally, to use the synthetic methods developed to prepare simplified structural analogues of the heliannuols that may retain allelopathic activity. 

Pharmacology Acamprosate is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of the amino acid neurotransmitter -aminobutyric acid and the amino acid neuromodulator taurine. 

Trimethoprim (Trimpex, Proloprim) is a structural analogue of the pteridine portion of dihydrofolic acid. It differs from the sulfonamides in that it acts at a second step in the folic acid synthetic pathway that is, it... 

Dysidea sp. from Bararin Island in the Philippines, has yielded the dysideaprolines A-F (341-346), proline-derived analogues of dysidenin (318). The barbaleucamides A (347) and B (348), which are structural analogues of the cyanobacterial metabolite barbamide, were also isolated. The structures were elucidated by NMR spectroscopic analysis. It is most probable that all of these compounds are derived from a symbiotic cyanobacterium found in close association with the Dysidea sp. [306]. 

FIGURE 13—30. Icon of acamprosate. A structural analogue of the amino acid taurine, acamprosate reduces the excitatory actions of glutamate at the NMDA—calcium channel complex. 

Twelve-residue peptides have been synthesized as structural analogues of the 63-74 fragment, which contains the Ca2+-specific binding site II. In one analogue, Phe-72 was replaced by tyrosine, and in the other Gly-66 was also substituted by serine. From the enhancement of Tb3+ emission, a 1 1 binding stoichiometry was confirmed, and association constants around 2x 10s dm3 mol-1 determined. NMR studies show that binding of La3+ induced considerable perturbation of the amide proton resonances of aspartate, tyrosine and glutamate residues.243... 

Another interesting example of C-C bond formation can be found in reports from Li and co-workers who, in 2004, described the preparation of an MIP with peroxidase-like activity capable of dimerising the homovanillic acid (HVA) (73) [49]. In this case a polymer was prepared by using the HVA substrate, instead of a TSA, as a template and a haemin unit as catalytic centre (74). The polymerisation was carried out in the presence of acrylamide and vinyl-pyridine in order to add extra functionalities aiding substrate recognition. The imprinted polymer showed an enzyme-like activity, as confirmed by adherence to the Michaelis-Menten saturation model, and it was inhibited by ferulic acid (75), a structural analogue of the substrate, which is also capable of inhibiting the natural peroxidase. 

Different cyclization reactions of ort o-ami no-substituted benzothiazepinones 54 lead to tricyclic derivatives 55, containing imidazole (X = CR), 1,2,3-triazole (X = N), or tetrahydropyrazine (X = CH2CH2) rings (Equation 3). These compounds are structural analogues of the anti-HIV product thiobenzimidazolone (TIBO) <1999EJM701>. 

E. Van der Eycken et al. explored a microwave-assisted Suzuki-Miyaura reaction to generate structural analogues of the apogalanthamine family... 

The thiosulfate ion, S2 O2- "3, is a structural analogue of the sulfate ion where one oxygen atom is replaced by one sulfur atom. The two sulfur atoms of thiosulfate thus are not equivalent. Indeed, the unique chemistry of the thiosulfate ion is dominated by the sulfide-like sulfur atom which is responsible for both the reducing properties and complexing abilities. The ability of thiosulfates to dissolve silver halides through complex formation is the basis for their commercial application in photography (qv). 

A classic example of competitive inhibition is the inhibition of succinate dehydrogenase by malonate, a structural analogue of succinate. Competitive inhibitors are usually structural analogues of the substrate, the molecule with which they are competing. They bind to the active site but either do not have a structure that is conducive to enzymatic modification or do not induce the proper orientation of catalytic amino acyl residues required to affect catalysis. Consequently, they displace the substrate from the active site and thereby depress the velocity of the reaction. Increasing [S] will displace the inhibitor. 

Smith MC, Barclay JE, Cramer SP, Davies SC, Gu W-W, Hughes DL, Longhurst S, Evans DJ (2002) Nickel-iron-sulfur complexes approaching structural analogues of the active sites of NiFe-hydrogenase and carbon monoxide dehydrogenase/acetyl-CoA synthase. Dalton Trans. 2641-2647... 

Meuleman DG, Hobbelen PM, Van Dinther TG et al. (1991) Antifactor Xa activity and antithrombotic activity in rats of structural analogues of the minimum antithrombin III binding sequence discovery of compounds with a longer duration of action than the natural pentasaccharide. Semin Thromb Hemost 17 (Suppl 1) 112—117 Millet J, Theveniaux J, Brown NL (1994) The venous antithrombotic profile of naroparcil in the rabbit. Thromb Haemost 72(6) 874—879... 

These reactions occur well without the enzyme (Chapter 36) but the enzyme accelerates this reaction by ah out a 106 increase in rate. There is no acid or base catalysis and we may suppose that the enzyme binds the transition state better than it binds the starting materials. We know this to be the case, because close structural analogues of the six-m embered ring transition state also bind to the enzyme and stop it working. An example is shown alongside—a compound that resembles the transition stale but can t react. 

Numerous oxo-molybdo-bis(dithiolene) and oxo-tungsto-bis(dithiolene) complexes have been synthesized and characterized as potential structural analogues of the active sites of the dimethyl sulfoxide reductase (DMSOR) and aldehyde oxidoreductase (AOR) families of mononuclear Mo and W enzymes [see Fig. 16 and Chapter 10 in this volume (50)]. The available IR and Raman data for the Mo and W complexes are summarized in Tables VII and VIII,... 

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