Aminobenzoic acids structure

Common Name N-Benzoyl-L-tyrosyl-p-aminobenzoic acid Structural Formula ... 

Bacteria require p-aminobenzoic acid to biosyn thesize folic acid a growth factor Structurally sul fanilamide resembles p-aminobenzoic acid and is mistaken for it by the bacteria Folic acid biosynthesis IS inhibited and bacterial growth is slowed suffi ciently to allow the body s natural defenses to effect a cure Because animals do not biosynthesize folic acid but obtain it in their food sulfanilamide halts the growth of bacteria without harm to the host... 

A chance observation made some time prior to the full structural elucidation of cocaine in fact led to one of the more important lasses of local anesthetics. It was found that the simple ethyl e. ter of p-aminobenzoic acid, benzocaine (25), showed activity. 1-. a local anesthetic. It is of interest to note that this drug, I 1rst introduced in 1903, is still in use today. Once the struc-iiire of cocaine was established, the presence of an alkanolamine iiiniety in cocaine prompted medicinal chemists to prepare esters "I aminobenzoic acids with acyclic alkanolamines. Formula 26 11 presents the putative relationship of the target substances with cocaine. 

The following molecular model is a representation of para-aminobenzoic acid (PABA), the active ingredient in many sunscreens. Indicate the positions of the multiple bonds, and draw a skeletal structure (gray = C, red = O, blue = N, ivory - H). 

The reaction of 2-aminobenzoic acid hydrazidcs with ortho esters gives 4-methyl-3//-1,3,4-benzotriazepin-5(4//)-ones 17 or 4-methyl-l//-l, 3,4-benzotriazepin-5(4//)-ones 18, depending on the structure of the hydrazide. Selected examples are given.359 11 360 361... 

Thus, in the first case, if the amine is o-aminobenzoic acid, an explosive diazonium salt with a zwitterion structure is obtained ... 

Figure 1.13 High-resolution STM image (50 nm x 50 nm, bias -1.14V, tunneling current 6.1 nA) showingthe faceted structure ofp-aminobenzoic acid on Cu(l 1 0). (Reprinted with permission from Ref. [47], Copyright 2003, Elsevier.)...

The reaction with m- and p-aminobenzoic acids results in the formation of 1,5,3,7-diazadiphosphacyclooctane (155), possessing the structure of a double betaine [Eq. (119)]. These compounds were obtained from bis(hydroxymethyl)phenylphosphine (89IZV1340). 

Changes in the pteridine ring affect the contacts between DHFR and the p-aminobenzoic acid (PBH) moiety. PBH maintains van der Waals contact with Phe31 in all four structures (1, 3, 5 and 6) with contact distances ranging within 0.4 A of one another. Contact is also observed with Leu54 in all four structures with distances ranging from 3.0 A to 2.8 A. Only in... 

Type 2 (see p. 370) is obtained by coupling diazotized aminobenzoic acid onto acetoacetarylide. The resulting acid is converted into the acid chloride and condensed with an aromatic diamine (see structure in the appendix). 

In contrast to humans, bacteria have the biochemical ability to synthesize folic acid from simpler molecules. Here we have a clear biochemical difference between human beings and infectious organisms that we can exploit to our benefit. The reaction catalyzed by an enzyme known as dihydropteroate synthetase, in which a complex heterocycle is linked to p-aminobenzoic acid, is key. Now recognize the structural similarity between sulfanilamide, or other sulfonamides, and p-aminobenzoic acid ... 

Given this structural similarity, it should not be surprising to learn that sulfanilamide competes with p-aminobenzoic acid for a binding site on the surface of dihydropteroate synthetase. Put another way, sulfanilamide binds to the enzyme where p-aminobenzoic acid should bind but no reaction occurs. The consequence is that a step in folic acid biosynthesis is disrupted and the bacterial cell is deprived of adequate folic acid. Nucleic acid synthesis, among other things, is disrupted, leading to a cessation of cell growth and division. The human immune system can mop up what remains. No similar consequences befall the human host since it cannot make folic acid in the first place and must get an adequate supply of this vitamin in the diet. 

Donald Woods discovered that sulphonamides exerted their action by inhibiting an enzyme used by bacteria to synthesise folic acid. The compound 4-aminobenzoic acid is the precursor for folic acid, and is structurally similar to sulphonamide. Bacteria that were unable to synthesise folic acid were unable to achieve de novo synthesis of purines for their DNA and RNA synthesis and hence could not proliferate. Such competitive inhibitors, which mimicked normal metabolites, became known as antimetabolites (many are used in cancer chemotherapy. Chapter 21). 

Figure 15.1 Structure of pterin. In the folates, pterin is linked to 4-aminobenzoic acid through at methylene bridge at posirion 6.

Mammals must obtain their tetrahydrofolate requirements from their diet, but microorganisms are able to synthesize this material. This offers scope for selective action and led to the use of sulfanilamide and other antibacterial sulfa drugs, compounds that competitively inhibit the biosynthetic enzyme (dihydropteroate synthase) that incorporates p-aminobenzoic acid into the structure (see Box 7.23). 

Tetracaine Tetracaine, the 2-diethylaminoethyl ester of 4-butylaminobenzoic acid (2.1.6), is also structurally analogous to procaine, in which the amino group of the benzene ring is replaced by a butylamine radical. The methods for its synthesis are the same as the above-mentioned methods for procaine or chloroprocaine, with the exception of using 4-butylaminobenzoic acid in place of 4-aminobenzoic acid. There is also a proposed method of synthesis that comes directly from procaine (2.1.1). It consists on its direct reaction with butyric aldehyde and simultaneous reduction by hydrogen using a palladium on carbon catalyst [6]. 

Sulfanilamide, whose structure is similar to the structure of p-aminobenzoic acid, competes with p-aminobenzoic acid for inclusion in the folic acid molecule. In short, by taking the place of p-aminobenzoic acid, it interferes with the biosynthesis of folic acid. As a result, the misled enzymes construct a false molecule of folic acid, which is not able to carry out the vital function of true folic acid. 

Sulfanilamides are antibiotics that serve as structural analogs of para-aminobenzoic acid (PABA), a substrate In the formation of folic acid by many bacteria. Substitution of the sulfanilamide compound In place of PABA In the reaction prevents formation of the critical coenzyme folic acid. 

Para-aminosalicylic Acid (PAS), like the sulfonamides (see Chapter 44), is a structural analogue of p-aminobenzoic acid (PABA). It is a folate synthesis antagonist that interferes with the incorporation of PABA into folic acid. PAS is bacteriostatic, and in vitro, most strains of M. tuberculosis are sensitive to a concentra-... 

In principle every compound with an amino and a carboxy group can be used for such purpose ranging from simple co-amino acids [e.g., 5-aminopentanoic acid (6-aminovaleric acid) (1, n = 3)]1541 or 6-aminohexanoic acid (e-aminocaproic acid) (1, n = 4)]135,57,4 791 and related derivatives of 3-aminobenzoic acid 14801 or more sophisticated structures. A few examples (1-6) are shown in Scheme 28. Numerous cyclic turn mimetics have been developed in the past years and for details on this subject the reader is directed to Vol. E 22c, Section 12. To explore the rigidification introduced by nonnatural amino acids or equivalent structures into cyclic peptides, a careful NMR conformational analysis is required, since frequently the so-called p-turn mimetics do not enable such turns to be established, conversely other secondary structure elements may be induced.14811... 

Problem 18.37 Deduce the structures of the azo compounds that yield the indicated aromatic amines on reduction with SnCl2 (a) p-toluidine and p-NH2-N,N-diMeaniline, (b) I mol of 4,4 -diaminobiphenyl and 2 mol of 2-hydroxy-5-aminobenzoic acid. -4... 

To date, over 10 000 structural analogues of sulphanilamide, the parent of all sulpha drugs, have been synthesized and used in the SAR studies. However, only about 40 of them have ever been used as prescribed drugs. Sulpha drugs are bactereostatic, i.e. they inhibit bacterial growth but do not actively kill bacteria. These drugs act on the biosynthetic pathway of tetrahydrofolic acid, inhibit dihydropteroate synthetase and mimic the shape of PABA (para-aminobenzoic acid). 

The basic formulas of the sulfonamides and their structural similarity to p-aminobenzoic acid (PABA) are shown in Figure 46-1. Sulfonamides with varying physical, chemical, pharmacologic, and antibacterial properties are produced by attaching substituents to the amido group (-S02-NH-R) or the amino group (-NH2) of the sulfanilamide nucleus. 

---