With Ester Side Chain

Suitable reagents have two amino groups separated by a carbon atom. One amino group makes a nucleophilic attack on the electrophilic carbon atom of the keto group, whereas the other, by adding to the carbonyl group of the ester substituent, forms a tetrahedral complex that starts the exchange of—NH2 for—OEt. 

2-Ethoxycarbonylcyclohexanone, refluxed with thiourea in ethanolic sodium methoxide ( ), furnished 2-thioxo-5,6,7,8-tetrahydroquinazolin-4-one in good yield.20 The same cyclohexanone and S-methylisothiuronium sulfate, in cold aqueous potassium hydroxide, gave a poor yield of 2-methylthio-5,6,7,8-tetrahydroquinazolin-4-one.21 

Similarly, 3-carbomethoxy-2-tetralone, when refluxed with guanidine carbonate in ethanol for 16 hr, provided a moderate yield of 2-amino-5,10- 

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As might be expected, a complex mixture of lactones corresponding to abstraction of a hydrogen atom from various sites along the methylene chain was obtained from the photolysis. The mixture of lactones was converted by dehydration, ozonolysis, and hydrolysis to a mixture of ketones. It was found that no functionalization occurs with ester side chains of less than nine carbon atoms. This is probably due to the inability of the carbonyl to approach any methylene closely enough to abstract a hydrogen. The data for side chains of nine carbons or greater is presented in Table 3.11. 

Philadelphia. This polymers, structurally a straight carbon skeleton with ester side chains, the esters being from quaternary ammonium substituted alcohols, are soluble in water, and the water solution has a viscosity of 2500 to 5000 centipoises in 5% aqueous solution at room temperature. Equivalent weight of the polymers based on the ammonium groups, are about 350-360 2)... 

Side group rotations become important in polymers with ester side chains, of which there are very many. Of technological significance is the low temperature transition in poly(methyl methacrylate). Another interesting conformation change is the boat-chair switch in cyclohexyl groups (Figure 5.5). 

Scheme 4 Possible combinations of two bifunctional components (AA + BB) and one monofunctional component in a Passerini-3CR, resulting in different repeat units (a) alpha-amide substituted polyesters, (b) alternating poly(ester-amide)s and (c) polyamides with ester side chains...

Antispasmodic activity, interestingly, is maintained even in the face of the deletion of the ethanolamine ester side chain. Reaction of anisaldehyde with potassium cyanide and dibutylamine hydrochloride affords the corresponding a-aminonitrile (72) (a functionality analogous to a cyanohydrin). Treatment with sulfuric acid hydrolyzes the nitrile to the amide to yield ambucet-amide (73). ... 

The transformation of the porphyrin intermediate 4 into a chlorin can be achieved after introduction of a C — C double bond into the 15-propanoate side chain of 4 to yield 5. The cyclization of 5 with participation of the 15-acrylic ester side chain under acidic conditions gives the chlorin 6 which is then transformed in a multistep reaction sequence into chlorophyll a. The driving force of chlorin formation from the porphyrin is believed to be the relief of steric strain at the sterically overcrowded porphyrin periphery which gives the desired trans arrangement of the propanoate side chain and the methyl group in the reduced ring. The total... 

However, upon dissolution, an epimerization of the anions can occur in the presence of acidic counter-ions. This is particularly true for 16a-16d [39]. The nature of the solvent (MeOH, CHCI3) plays a crucial role on the kinetics of epimerization and the position of the resulting equilibrium. For anions made with a 2R, 3R) tartaric backbone, a A configuration is always preferred in MeOH the selectivity, obtained after a slow equilibration, being independent of the nature of the ester alkyl chain (diastereomeric ratio (d.r.) 3 1). However, in chloroform, the A diastereomer is rapidly obtained and the selectivity is best if the ester side chain is sterically demanding (d.r. 2 1 to 9 1 from 16a to 16d) (Scheme 16). 

A methyl group can be placed on cobalt in dicyano[cobyrinic acid heptamethyl ester] when it is treated with excess methyl magnesium iodide (the ester side chains being converted into tertiary alcohol groups). The alkylation could also be achieved using lithium alkyls (176). Presumably this reaction would be successful with any corrinoid which is soluble in solvents compatible with Grignard reagents. 

Compression-molded devices of poly(N-palmitoyl hydroxyproline ester) (side chain length 16 carbons), poly(N-decanoylhydroxy-proline ester) (side chain length 10 carbons), and poly(JN-hexanoyl-hydrox roline ester) (side chain length 6 carbons) were prepared with dye contents of 1,5,10, and 20% of either -nitroaniline or acid orange. Release curves were obtained by placing the loaded devices into phospate buffer (pH 7.4) at 37 C. The amount of released dye was followed spectrophotometrically in the usual fashion. 

The authors concluded that the side reactions normally observed in amine-initiated NCA polymerizations are simply a consequence of impurities. Since the main side reactions in these polymerizations do not involve reaction with adventitious impurities such as water, but instead reactions with monomer, solvent, or polymer (i.e., termination by reaction of the amine-end with an ester side chain, attack of DMF by the amine-end, or chain transfer to monomer) [11, 12], this conclusion does not seem to be well justified. It is likely that the role of impurities (e.g., water) in these polymerizations is very complex. A possible explanation for the polymerization control observed under high vacuum is that the impurities act to catalyze side reactions with monomer, polymer, or solvent. In this scenario, it is reasonable to speculate that polar species such as water can bind to monomers or the propagating chain-end and thus influence their reactivity. 

An effect similar to that of cetyltrimethylammonium bromide micelles can be realized through the use of microgels with trimethylamino side-chain function and this may then allow solid supported microgels to be used in a continuous reaction. Evans et al. (1995) have utilized microgels incorporating 2-tetradecyl dimethyl amino/ethyl methacrylate bromide, which solubilizes aryl laurate esters in an aquous solution and catalyses the alkaline hydrolysis. 

For the sake of clarity, the resonances belonging to the individual groups have been isolated from the data and presented in tables III and IV. Table III shows the resonances associated with the side chain (carbons 16-19). Examination of the data reveals that each side chain presents a unique set of resonances (Table III). For example, resonances at 6 166.5, 136.8, 126.5 and 18.3 uniquely describe the side chain associated with elegin (XII), repdiolide (XIV) and epoxyrepdiolide (VII), i.e., a side chain ester with a double bond between C-17 and C-18. Likewise for each of the other three side chains one can completely describe them on the basis of their 33c-NMR spectra alone. 

Biodegradable polyurethanes have been proposed and studied before (9-72). The difference in our study is the inclusion of a phosphoester linkage instead of the commonly used polyester component. This seems to provide more flexibility as the side chain of the phosphate or phosphonate can be varied. For controlled drug delivery applications, drugs can be linked to this site to form a pendant delivery system. Moreover, for certain medical applications, fast degradation rate is obtainable by the introduction of these hydrolyzable phosphoester bonds. With the LDI based polyurethanes, drugs or other compounds of interest can also be coupled to the ester side chain of the lysine portion. 

Figure 6.2 The trifunctional reagent sulfo-SBED reacts with amine-containing bait proteins via its NHS ester side chain. Subsequent interaction with a protein sample and exposure to UV light can cause crosslink formation with a second interacting protein. The biotin portion provides purification or labeling capability using avidin or streptavidin reagents. The disulfide bond on the NHS ester arm provides cleavability using disulfide reductants, which effectively transfers the biotin label to an unknown interacting protein.

In contrast, with penicillins, cephalosporins, and monobactams where the substituents are cis to each other across the C3 - C4 bond, clockwise rotation can occur without conflict with protein side chains, and will leave the path open for the water molecule to attack and hydrolyze the ester group in B (Scheme 10). Thus, czs-substituted monobactam, as well as penicillins and cephalosporins are rapidly hydrolyzed by class C enzymes (Scheme 10). If this rotation could be prevented by a suitable structural modification, the access of the water molecule to the ester bond will be blocked, which would result in increased stability of the acyl-enzyme complex. 

A-Aroyloxy-A-benzyloxybenzamides 28, with variation on the ester side chain... 

A second method of activating the acid for esterification (see Section 7.6) is as the mixed anhydride. The mixed-anhydride reaction had been employed decades ago for preparing activated esters. However, it was never adopted because of its unreliability and the modest yields obtained. The method was fine-tuned (Figure 7.12), after reliable information on the properties of mixed anhydrides was acquired (see Section 2.8). Tertiary amine is required for esterification of the mixed anhydride to occur. The method is generally applicable, except for derivatives of asparagine, glutamine, and serine with unprotected side chains. The base also prevents decomposition that occurs when the activated derivative is a Boc-amino acid (see... 

The spacer arm length between the hapten and the carrier is in the range of 6 to 8 A, which should eliminate any steric interference with carrier side chains. According to the protocol described by Schultz the haptens were coupled to BSA and KLH via A-(3-dimethylaminopropyl)-A -ethylcarbodiimide or the N-hydroxysuccinimide ester at pH 5.5 in water. Other coupling strategies include substitution with diazonium salts and reductive amination. The ratio of hapten-carrier range between 8 and 15 haptens per carrier. 

The nucleophile will be the enolate anion from ethyl acetoacetate, which attacks the P-carbon of the electrophile, generating an addition complex that then acquires a proton at the a-position with restoration of the carbonyl group. The product is a 8-ketoester with an ester side-chain that has a... 

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

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