“…The choice of the cyanylating reagent has a critical effect on the course of the reaction (24,25). For the 8-diazo-flavins, in our hands, either sodium cyanide or cuprous cyanide alone were ineffective.…”
A high potential analog of riboflavin with a cyano function at the 8-position was synthesized by employing novel reaction conditions, starting from 8-amino-riboflavin. This was converted to the FAD level with FAD synthetase. The reduced 8-CN-riboflavin, unlike normal reduced flavin, has a distinctive absorption spectrum with two distinctive peaks in the near ultraviolet region. The oxidation-reduction potential of the new flavin was determined to be -50 mV, ϳ160 mV more positive than that of normal riboflavin. The 8-CN-riboflavin and 8-CN-FMN were found to be photoreactive and need to be protected from exposure to light. However such complications were not encountered with protein-bound flavins. The apoproteins of flavodoxin and Old Yellow Enzyme (OYE) were reconstituted with the 8-CN-FMN and apoDAAO was reconstituted with 8-CN-FAD. Spectral properties of the enzyme-bound neutral and anionic semiquinones were determined from these reconstituted proteins. In the case of 8-CN-FMN-OYE I, it was shown that the comproportionation reaction of a mixture of reduced and oxidized enzyme bound flavin is very rapid, compared with the same reaction with native protein, resulting in ϳ100% thermodynamically stable anionic semiquinone. In the case of 8-CN-OYE I, it was shown that the rate of reduction of the enzyme bound flavin by NADPH is ϳ40 times faster, and the rate of reoxidation of reduced enzyme bound flavin by oxygen is an order of magnitude slower than with the normal FMN enzyme. This is in accord with the high oxidation-reduction potential of the flavin, which thermodynamically stabilizes the reduced enzyme.
“…The choice of the cyanylating reagent has a critical effect on the course of the reaction (24,25). For the 8-diazo-flavins, in our hands, either sodium cyanide or cuprous cyanide alone were ineffective.…”
A high potential analog of riboflavin with a cyano function at the 8-position was synthesized by employing novel reaction conditions, starting from 8-amino-riboflavin. This was converted to the FAD level with FAD synthetase. The reduced 8-CN-riboflavin, unlike normal reduced flavin, has a distinctive absorption spectrum with two distinctive peaks in the near ultraviolet region. The oxidation-reduction potential of the new flavin was determined to be -50 mV, ϳ160 mV more positive than that of normal riboflavin. The 8-CN-riboflavin and 8-CN-FMN were found to be photoreactive and need to be protected from exposure to light. However such complications were not encountered with protein-bound flavins. The apoproteins of flavodoxin and Old Yellow Enzyme (OYE) were reconstituted with the 8-CN-FMN and apoDAAO was reconstituted with 8-CN-FAD. Spectral properties of the enzyme-bound neutral and anionic semiquinones were determined from these reconstituted proteins. In the case of 8-CN-FMN-OYE I, it was shown that the comproportionation reaction of a mixture of reduced and oxidized enzyme bound flavin is very rapid, compared with the same reaction with native protein, resulting in ϳ100% thermodynamically stable anionic semiquinone. In the case of 8-CN-OYE I, it was shown that the rate of reduction of the enzyme bound flavin by NADPH is ϳ40 times faster, and the rate of reoxidation of reduced enzyme bound flavin by oxygen is an order of magnitude slower than with the normal FMN enzyme. This is in accord with the high oxidation-reduction potential of the flavin, which thermodynamically stabilizes the reduced enzyme.
“…Subsequent palladium-catalyzed Suzuki−Miyaura coupling of 4 with phenylethynyl boronate derivatives, generated in situ under basic conditions with MeO-9-BBN, produced 5‘-phenylethynyl analogues in good yields (Scheme B). Many of the starting phenylacetylenic compounds are commercially available; others were generated via Sonogashira or Sandmeyer , conditions. The resulting coupled products 5a − k were then subjected to acidic hydrolysis of the methoxymethyl phenolic protecting group followed by basic saponification of the methyl ester to afford the desired 5‘-phenylethynyl GC-1 analogues 6a − k as outlined in Scheme B.…”
Selective thyroid hormone modulators that function as isoform-selective agonists or antagonists of the thyroid hormone receptors (TRs) might be therapeutically useful in diseases associated with aberrant hormone signaling. The most potent thyroid hormone antagonist reported to date is NH-3. To explore the significance of the 5'-p-nitroaryl moiety of NH-3 and understand what chemical features are important to confer antagonism, we sought to expand the structure-activity relationship data for the class of 5'-phenylethynyl GC-1 derivatives. Herein, we describe an improved synthetic route utilizing palladium-catalyzed chemistry for efficient access to a series of 5'-phenylethynyl compounds with varying size and electronic properties. We prepared and tested sixteen analogues for TR binding and transactivation activity. Substitution at the 5'-position decreased binding affinity, but retained TRbeta-selectivity. In transactivation assays, the analogues displayed a spectrum of agonist, antagonist, and mixed agonist/antagonist activity that correlated with electronic character in a Hammett analysis between sigma substituent value and TR modulation. Analogues NH-5, NH-7, NH-9, NH-11, and NH-23 displayed full antagonist activity with reduced potency compared to NH-3, indicating the nitro group is not required for antagonism. However, para-substitution with strong electron withdrawing properties on the 5'-aryl extension is important for antagonist activity, and antagonist potency-but not ligand receptor binding-was found to correlate linearly with the sigma values for the electron withdrawing substituents.
“…The textile industry has recently faced pressure to reduce the amount of electrolytes and colored wastewater released into the environment, thus stimulating research into ways to alleviate these concerns. These ideas include use of ion-exchange resins; solid−solid reactions; polyethylene glycol solvent; clay catalysts, polymers, or resins; or carbonic acid from water and CO 2 for catalysis. ,, 1 Alkylcarbonic Acid Formation and Proton Dissociation Equilibria…”
Despite widespread use, homogeneous acid catalysis has the drawback of requiring downstream neutralization, resulting in salt waste. Methylcarbonic acid is a self-neutralizing acid that forms in situ in methanol/CO 2 systems at mild pressures (10-47 bar) and then decomposes by depressurization. In the work presented here, methylcarbonic acid catalyzes the diazotization of aniline, which is either coupled with N,N-dimethyl aniline to form methyl yellow or reacted with iodide to form iodobenzene. The syntheses of methyl yellow and iodobenzene represent a class of industrially important reactions.
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