Lipophilicity methyl groups

Methyl group (Section 2 7) The group —CH3 Mevalonic acid (Section 26 10) An intermediate in the biosyn thesis of steroids from acetyl coenzyme A Micelle (Section 19 5) A sphencal aggregate of species such as carboxylate salts of fatty acids that contain a lipophilic end and a hydrophilic end Micelles containing 50-100 car boxylate salts of fatty acids are soaps Michael addition (Sections 18 13 and 21 9) The conjugate ad dition of a carbanion (usually an enolate) to an a 3 unsatu rated carbonyl compound... 

The taste properties of the di-O-methylhexopyranosyl derivatives, like those of the corresponding deoxy sugars, are never sweet, and always bitter. As with the deoxy sugars, this is possibly the result of increased lipophilicity of the molecule. In sucrose, however, the presence of two methyl groups on the D-glucopyranosyl or the D-fructofuranosyl group does not seem to cause any marked bitterness (see Table XVIII). 

Tarzia et al. [69, 70] have recently reported the FAAH inhibitory activity of a series of alkylcarbamic acid aryl esters. The starting point for their studies was the known serine hydrolase inhibitor carbamyl (51) that had no activity at FAAH. Replacement of the small methyl group of carbamyl (51) with more lipophilic groups and, in particular, bulky lipophilic groups resulted in increased affinity at FAAH (Table 6.6). Exploration of replacements of the naphthyl moiety revealed that replacement with a biphenyl group resulted in improved affinity and in particular, the 3-biphenylyl group proved effective... 

In polar solvents, the structure of the acridine 13 involves some zwitterionic character 13 a [Eq. (7)] and the interior of the cleft becomes an intensely polar microenvironment. On the periphery of the molecule a heavy lipophilic coating is provided by the hydrocarbon skeleton and methyl groups. A third domain, the large, flat aromatic surface is exposed by the acridine spacer unit. This unusual combination of ionic, hydrophobic and stacking opportunities endows these molecules with the ability to interact with the zwitterionic forms of amino acids which exist at neutral pH 24). For example, the acridine diacids can extract zwitterionic phenylalanine from water into chloroform, andNMR evidence indicates the formation of 2 1 complexes 39 such as were previously described for other P-phenyl-ethylammonium salts. Similar behavior is seen with tryptophan 40 and tyrosine methyl ether 41. The structures lacking well-placed aromatics such as leucine or methionine are not extracted to measureable degrees under these conditions. 

We first attempted to make the ammonium salts more stable using steric hindrance. We prepared a variety of sterically encumbered ammonium salts via the sequence shown in Equation 2. Although we could prepare a vau iety of hindered tertiary amines, successful quaternlzatlons were achieved only with methyl groups. These salts were more stable to phenoxlde than n-Bu NBr by factors of 10-50, demonstrating that steric hindrance can ay a significant part in stabilization of phase transfer catalysts. However, none of these salts were more effective than n-Bu NBr as phase transfer agents, probably due to their less lipophilic nature, and we turned our attention to other systems. 

Initially, it was found that introducing a methyl group at the 1-position and a methyl or phenyl substituent at the 2-position of the indole ring in this series produced only small changes in activity, despite a marked increase in lipophilicity of the phenyl-substituted compounds Table 7.1). 

Structural features such as electrical charge, hydroxyl groups in the side-chains and amino atoms of the amide groups reduce the lipophilicity (increase the hydrophilicity) whereas additional methyl groups sitting on amino moieties or free positions on the benzene ring increase the fipophilicity. Biliary contrast agents with a free position have > 5. 

The PAL activity that is necessary for lignin formation occurs in the cytoplasm or bound to the cytoplasmic surface of the endoplasmic reticulum membranes. The cinnamic acid produced is probably carried on the lipid surface of the membranes, since it is lipophilic, and it is sequentially hydroxylated by the membrane-bound hydroxylases (47,50). In this way there is the possibility of at least a two-step channeling route from phenylalanine to p-coumaric acid. The transmethylases then direct the methyl groups to the meta positions. There is a difference between the transmethylases from angiosperms and those from gymnosperms, since with the latter... 

The lack of hydroxyl moieties and the introduction of a methyl group to the side chain makes the molecule more lipophilic and thereby increases its ability to enter the system after oral application and cross the blood-brain barrier. This is the case with indirect sympathomimetic drugs of the amphetamine type. The methyl substituent in the side... 

A lipophilic gel, namely, Sephadex LH-20, has found application in studies of partially acetylated dextrans. In describing a modified procedure for the replacement of the O-acetyl groups in such dextrans by O-methyl groups prior to acid hydrolysis and identification of the fragments (which indicates the distribution of the substituents in... 

The results in Table I agree with the postulated reaction mechanism. In most of cases two, isomeric pyridones 4 and 5 are formed. The structure of the N-substituent also contributes to the ratio of products, such as in the case of a series of 3-tcrt-butylpyridinium salts where the percentage of 2-pyridone decreases from 14% (N-methyl) to 0% if the N-methyl group is replaced by sterically larger and more lipophilic substituents R . Substituents like CO2H, COMe, COPh, and NOj result in the pyridone function being specifically introduced into the 6-position, so that only 5 can be obtained after Decker oxidation. Only one case (R = Me, R = CN) has been reported (7IJCS(B)131) in which traces of a 4-pyridone 6 were formed. 

N-1 Methyl group Increased lipophilicity shorter duration... 

Muller, N., When Is a Trifluoromethyl Group More Lipophilic Than a Methyl Group Partition Coefficients and Selected Chemical Shifts of Aliphatic Alcohols and Trifluor-oalcohols. J. Pharm. Sci., 1986 75, 987-991. 

The pharmacological efficacy of adamantane derivatives may be attributed to several factors. The high lipophilic character associated with high molecular weight hydrocarbons appears to be coupled with a highly precise and specific donor-receptor interaction between adamantane and the receptor proteins. Addition of methyl groups to the adamantane nucleus apparently destroys the precision with which the adamantyl group fits into the receptor site 346> 347). 

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