Carboxylic acid derivatives, functional groups among

Another consequence of the reactivity differences among carboxylic acid derivatives is that only esters and amides are commonly found in nature. Acid halides and acid anhydrides undergo nucleophilic attack by water so rapidly that they can t exist in living organisms. Esters and amides, however, are stable enough to occur widely. All protein molecules, for example, contain amide functional groups. 

The oxidation of aldehydes (alkanals) and ketones (alkanones) has been reviewed extensively [1-3], and there are compilations based on reagent types [4-8] and oxidation methods for most functionalized compounds including those having carbonyl groups. Books [9, 10] and comprehensive review articles [11-16] on carboxylic acids and their derivatives also provide important background information on the oxidation of carbonyl compounds. This account will focus exclusively on the synthesis of carboxylic acid derivatives. After a brief summary of the well-estabHshed methods, new directions in oxidative transformations of carbonyl compounds will be described. Among these, in particular, catalytic [17, 18] and asymmetric versions will be emphasized. 

Carboxylic acids are easily converted to a variety of acid derivatives. Each derivative contains the carbonyl group bonded to an oxygen or other electron-withdrawing element. Among these functional groups are acid chlorides, esters, and amides. All of these groups can be converted back to carboxylic acids by acidic or basic hydrolysis. 

Among these, in particular, the acetate [17] and the silyloxyl [31] derivatives are often used as the protecting groups for the hydroxyl (alcohol) function. For example, polymers of 2-acetoxyethyl vinyl ether are readily transformed into a polyalcohol, poly(2-hydroxyethyl vinyl ether), by alkaline hydrolysis [17]. Due to the polar pendant functions, the polymers are of course hydrophilic and often water-soluble, and serve as hydrophilic segments in so-called amphiphilic polymers, as will be discussed later (Sections III.D and VI.B.5). Other important protecting groups include the malonate [23] and the imides [29,30], which lead to polymeric carboxylic acids and amines, respectively (Scheme 1). 

Direct derivatives of carboxylic acids are different functional groups which maintain an acidic proton and a hydrogen bond acceptor (the carbonyl) in order to have similar specific interactions with the receptor. Among the most common direct derivatives can be listed the hydroxamic acids (R—CO— NH—OH), the acylcyanamides (R—CO— NH—CN) and the acylsulfonamides (R—CO— NH—SO2—R ) (Table 15.11). 

Recently, Lazo and co-workers reported a combinatorial library of PTPIB inhibitors based on a pharmacophore derived from the structure-activity relationships for several natural product inhibitors of PSTPases such as oka-daic acid, microcystins and calyculin A [425, 426], The pharmacophore model involved a carboxylate, a non polar aromatic group and hydrogen-bond acceptors and donors and was used as a platform for functional group variation. Among the 18 library compounds generated by parallel solid-phase chemistry, a non-competitive inhibitor for PTPIB was identified (library 41, Kj=0.85 jiM) [425] and as well a serine/threonine phosphatase inhibitor (library 42, IC50 < 100 /iM) [426],... 

The amino acids are among the most important molecules of biochemical interest, since they constitute the building blocks of peptides and proteins. Most of their outstanding properties are due to th6 amphoteric nature which derives from the presence, in their structure, of two functional groups of different polarity (the amino, NH2 and the carboxyl, COOH, groups). These group are also responsible of the existence of two tautomeric forms, neutral (NT) and zwitterionic (ZW) forms. 

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