Carboxyl substituent

Because the integrity of the dihydrothiazine ring and its C-4 carboxyl substituent is crucial to useful antimicrobial activity, reactions involving this part of the cephalosporin molecule are usually undesirable. The possibilities for sulfur oxidation or alkylation, substitution at C-2 which is adjacent to both sulfur and a double bond, double bond isomerization and addition reactions, and the influence of a free carboxylic acid must all be considered in designing reactions to selectively modify other cephalosporin functionalities. 

Atractyligenin and its sulfated glucoside (actractyloside) are toxins which block the transport of ADP into mitochondria and which occur in the coffee bean. Atractyligenin was synthesized following a multistrategic retrosynthetic plan in which the disconnection of ring B was a major objective. Novel stereocontrolled processes were employed for the critical cyclization to form the tetracarbocyclic network and for introduction of the carboxylic substituent. 

Cyclizations, which failed to occur under thermal conditions, have been forced by using strong acids as solvent. Such cyclizations required careful temperature control in order to cyclize while maintaining the 3-carboxyl substituent. ... 

Since the FeCp(C6H6)+ unit is robust towards oxidation even in concentrated sulfuric acid, oxidation of alkyl substituents upon boiling in aqueous KMn04 solution can be achieved and leads to carboxylic substituents. The mesitylene complex can be oxidized to the mono-, di-, or tri-carboxylic add depending upon the reaction conditions. In the latter case, the decomplexed trimesic acid is obtained [106, 107] Scheme XXII ... 

However, the hydride reduction of FeCp(arene)+ salts [124, 125] gives [FeCp(r 5-cyclohexadienyl)] complexes [125, 126] (via an ET mechanism [127] for the directing effect of substituents see Refs. [126, 128-130]. The electrochemical reduction of the carboxylic substituents at an Hg cathode in water leads to the primary alcohol [131-133] Eq. (39) ... 

The molecular structure of this compound determined by X-ray diffraction analysis reveals a significant contribution of the resonance form b (Scheme 34) to the osmium alkenyl bond, which is improved by the presence of the carboxyl substituent.71... 

Using the alternating deposition of the amphiphiles with a carboxyl substituent and arachidic add, noncentrosymmetric LB films (hetero Y-type) were prepared, and molecular orientation and second-order optical nonlinearity in the LB films were evaluated with the linear dichroism [4] and the second-harmonic generation (SHG) measurements, respectively. The SHG measurement procedure is mentioned in the section 1.3. 

The antibodies can also act like entropy traps by stabilizing a particular conformation of a substrate that is favorable to the formation of the TS. It is the case of the antibody 1F7 catalyzing the transformation of chorismate into prephenate," which stabilizes, thanks to several hydrogen bonds and an ionic bond between an arginine (Arg H95) and a carboxylate substituent of the substrate, the conformation of the chorismate which will give rise to the TS in a chair conformation for this reaction (Figure 11). 

Figure 8. Tertiary phosphines with carboxyl substituents...

Two traditional methods have been used to Introduce a carboxyl substituent at C-5 of uracil. 0ns iasolves bromlnatlon at C-5, metalatlon via a lithium-halogen exchange, and finally quenching with carbon dioxide (32) to give the C-5 carboxylic acid. The... 

More powerful directing groups such as those based on amides and sulphonamides are successful with pyridines as with carboxylic rings, and will not be discussed separately. The enhanced acidity of pyridine ring protons makes the simple carboxylate substituent an ideal director of lithiation in pyridine systems . The pyridinecarboxylic acids 232-234 are deprotonated with BuLi and then lithiated with an excess of LiTMP all the substitution patterns are lithiated nicotinic acid 233 is lithiated in the 4-position (Scheme 113). The method provides a valuable way of introducing substituents into the picolinic, nicotinic and isonicotinic acid series. 

The VCD spectra of a series of chiral allenes have been recorded at the University of Minnesota using a dispersive VCD instrument (113). The spectrum of one of these compounds has been verified by FTIR-VCD (23). The molecules have a phenyl and a carboxyl substituent on opposite ends of the allene, and alkyl or hydrogen substituents in die remaining two positions. All the corresponding (S)-(+) enantiomers, 46, exhibit a single positive VCD feature and the (/ )-(-) enantiomers, 47, a negative VCD feature, at 1945 cm , with an anisotropy ratio of ca. 4 X 10 . 

A fairly general route to 1,2-dihydroazocines (64) is provided by the [2+2] cycloaddition of DMAD to 1,2-dihydropyridines (62) (74JCS(Pi)2496,77JOC2903). The reaction gives good yields of the dihydroazocine-6,7-dicarboxylates with N- alkyl, -aryl or functionally substituted removable protective groups. Other substituents can be present at C-3 or -4 in the pyridine, but carboxyl substituents at N-l or C-5 of the pyridine reduce the enamine character, and Diels-Alder addition of the acetylene occurs at the diene system. The [4.2.0] bicyclic intermediates (63) can be detected at -10 to 0°C by NMR warming to 20 °C causes complete conversion to (64). 

Cycloalkanes with carboxyl substituents are named as cycloalkanecar-boxylic acids. Unsaturated acids are named using the name of the alkene with -e replaced with -oic acid. The chain is numbered starting with the carboxyl group, a number designates the location of the double bond and Z or E is used. 

An approach that affords cyclohexyl rings, with single carboxylate substituents, and is suitable for the preparation of some carbahexopyranoses (pseudosugars) depends on the initial condensation of O-substituted pentoses in the aldehydo forms with dimethyl malo-nate to give atkenes [17]. Thus, 2,3,4-tri-0-benzyl-5-0-f-butyldiphenylsilyl-D-ribose 29 (Scheme 8) can be converted to the alkene 30 in 85% yield by application of the... 

Table C2.1.1 Common Amino and Carboxyl Substituents Used with Various Synthetic Amino Acid and Peptide Substrates for Peptidases...

Chiral Rh(II) oxazolidinones Rh2(BNOX)4 and Rh2(IPOX)4 (25a,b) were not as effective as Rh2(MEPY)4 for enantioselective intramolecular cyclopropanation, even though the steric bulk of their chiral ligand attachments (COOMe versus i-Pr or CH2Ph) are similar. Significantly lower yields and lower enantioselectivides resulted from dinitrogen extrusion from prenyl diazoacetate catalyzed by either Rh2(4.S -lPOX)4 or Rh2(4S-BNOX)4. This difference, and those associated with butenolide formation [91], can be attributed to the ability of the carboxylate substituents to stabilize the carbocation form of the intermediate metal carbene (3b), thus limiting the Rh2(MEPY)4-catalyzed reaction to concerted carbene addition onto both carbon atoms of the C-C double bond. 

Again toluene is a suitable starting material, with its methyl group serving as the source of the carboxyl substituent. The orientation of the substituents in the final product requires that the methyl group be retained until the final step. 

Figure 6 Examples of simplifying molecular structures for the purpose of speeding calculations on the models. The extraneous side chains in cephalosporins and gemcita-bine are replaced by smaller groups (not all hydrogens are shown explicitly). The point is to retain only those parts of the compounds that deal directly with the electronic questions being studied. Side chains do affect the chemical and biological properties of a compound, but would produce a more or less constant effect on the electronic structure of the model structure retained. In the cephalosporins, the 7-acylamido and 4-carboxylate substituents can be replaced by NH2 and H, respectively. Substituents at the 3 position of cephalosporins include H, CH3, Cl, acetoxymethyl, arylthiomethyl, etc.

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