Carboxylates, biological methylation

Pharmaceuticals and Agrochemicals. Thioglycohc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351 -19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

Finally, the quinoline ring can be methylated at the 3 position with retention of biologic activity. The starting quinoline is prepared by the same scheme as that used for the desmethyl compound by substituting the methylated oxosuccinate ester, S6, in the sequence. The initial quinoline carboxylate (87) is taken on to the dichloro compound (88) by the standard reactions. Condensation with the ubiquitous diamine (76) affords sontoquine (89)... 

Biological activity tests on organotin(lV) complexes with a potent antihypertensive agent, captopril[(2S)-l-[(2S)-2-methyl-3-sulfanyl propanoyl]pyrroli-dine-2-carboxylic acid cap], were carried toward the embryos of C. intestinalis. The main results obtained were as follows ... 

On the analogy of the physicochemical relation, one was led to define a biological Hammett equation which related the equilibrium constant of the drug-receptor complex to the electronic a parameters of the substituents (e.g. chlorine, bromine, methyl, ethyl, hydroxyl, carboxyl, acetyl, etc.) of the drug molecule. Since the equilibrium constant of a drug-receptor complex is reflected by the biological activity, this led to the first extrathermodynamic relationship in QS AR ... 

Wong and co-workers have prepared various quaternary cx-nitro-cx-methyl carboxylic acid esters by the palladium-catalyzed allylic alkylation of a-nitropropionate ester (Eq. 5.59). The products can be kinetically resolved by using cx-chymotrypsin and are converted into optical active a-methyl cx-amino acids. Such amino acids are important due to the unique biological activity of these nonproteinogenic a-amino acids.82... 

The PCBM methyl ester can be used for coupling amine-containing ligands after removal of the methyl group and activation of the carboxylate using a number of different reaction strategies. Hummelen et al. (1995) successfully coupled cholestanol and histamine to the fuller-ene-PCBM derivative (after acid chloride formation) for use in fabrication of photodetectors and biological studies, respectively. For specific applications of PCBM-fullerenes, see Shaheen et al. (2001), Brabec et al. (2001), Yu et al. (1995), Mecher et al. (2002), Meijer et al. (2003), van Duren et al. (2004), and Anthopoulos et al. (2004). 

The Ras proteins are synthesized as biologically inactive, cytosolic precursor proteins. They are then modified by several post-translational processing steps at the carboxyl terminal end and thereby converted into biologically active proteins localized at the plasma membrane. The cysteine of the C-terminal CAAX sequence (C is cysteine, A is generally an aliphatic amino acid, and X is methionine, serine, alanine, or glutamine) is first enzymatically S-farnesylated the AAX part is then cleaved off by a specific protease, and the free C-terminal cysteine is finally converted into a methyl ester (Scheme 1). 

Non-natural ACC derivatives have been synthesized in order to test their eventual biological activity. Thus, in alkyl-ACC derivatives the alkyl and carboxyl groups must be in trans positions to be metabolized by plant tissue [111a]. For instance, the trans-methyl-ACC 80 serves as a good inhibitor of ethylene... 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

Methyl-3,4-dihydro-2tf-pyrido[l,2-a]pyrimidin-2-one is used in fluorescence (chiral) derivatization of carboxylic acids in HPLC with different 2-substituted 2H-benzotriazoles 688 in the presence of 2-bromo-1-ethylpyridinium tetrafluoroborate at room temperature (89MI2, 89MI15). This sensitive method has proved useful for the determination of carboxylic acids (e.g., ibuprofen) in small amounts of biological samples (89MI2). 

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