Acetic acid derivatives structure

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

I he potent antiinflammatory action exerted by many aryl acetic acid derivatives has led to the continued exploration of this class. It is apparent from a consideration of the structures of compounds that have become prominent that considerable structural latitude is possible without loss of activity. 

The unexpected 1,5-benzothiazepine derivatives 135, with an exocyclic substituted double bond at the 4-position, were obtained in moderate yields (e.g. 135, R = 4-Me, 51%) on reaction of 134 with the aminothiol 136 in acetic acid. The structure of the products was confirmed by detailed ID and 2D NMR experiments <06H(68)1319>. 

Nabumetone is the only nonacid NSAID in current use it is converted to the active acetic acid derivative in the body. It is given as a ketone prodrug that resembles naproxen in structure (Figure 36-1). Its half-life of more than 24 hours (Table 36-1) permits once-daily dosing, and the drug does not appear to undergo enterohepatic circulation. Renal impairment results in a doubling of its half-life and a 30% increase in the area under the curve. 

An alternative synthesis of ( )-a- and ( )--y-lycoranes (57 and 93) commenced with the 2-oxocyclohexyl acetic acid derivative 114 obtained by the alkylation of the enamine derived from 113 (Scheme 10) (116). Refluxing the oxime of 114 with zinc dust in glacial acetic acid afforded a mixture of the lactams 115, 116, and 117 in an approximate ratio of 4 6 3. The structure of 115 was verified by catalytic hydrogenation to give the lactam 118, which had previously been converted to ( )-a-lycorane (57). When the lactam 116 was subjected to sequential catalytic hydrogenation, hydride reduction, and Pictet-Spengler cyclization, ( )-y-lycorane (93) was obtained. A more efficient route to ( )-a-lycorane (57) involved refluxing the ketone 114 first with benzylamine in xylene and then with 87% formic acid to furnish the unsaturated lactam 119. 

Acetic Acid Derivatives and Related Substances (indometacin, diclofenac, sulindac, etodolac, aceclofenac) and structural analogue (lumiracoxib)... 

Decarbonylations of furfuraldehyde to furan continue to be of commercial interest and various new catalysts have been recommended.253 Decarboxylations are still occasionally useful,254 and the selective decarboxylation of furan-3,4-dicarboxylic acid to furan-3-carboxylic acid is said to be much improved by omitting any solvent.255 The easy decarboxylation of furan acetic acid derivatives is formulated in structure 139, although the acidic conditions need not preclude ring opening.2553... 

Furthermore, If carboxylic acid salts are generated in the reaction, these can react with the 5-carbonyl of an NCA to generate a carboxylic acld-carboxyllc acid chain end. As has already been shown by Mlwa and Stahman (64), such structures have acylatlng capability. The formation of hydantoln acetic acid derivatives from NCA s in DMF solution Is a rather favorable process (65) and this Is therefore also a likely source of acylatlng capability In the systems studied by Pegglon. 

Semisynthetic Penicillins. Just as the independent lines of inquiry of Dubos, Waksman, and the Oxford group converged to open the antibiotic era, the period of semisynthetic penicillin discoveries was initiated by a similar convergence. As an outgrowth of the early observation that the chemical nature of the penicillins produced by fermentation was influenced by the composition of the growth medium, the preparation of biosynthetic penicillins was accomplished by adding substituted phenyl-acetic acid derivatives (and related structures) to penicillin fermentations. By this method Behrens and co-workers at the Eli Lilly Co. had by 1948 prepared some 30 penicillins modified in the acyl moiety (64). 

Since, in general, only monosubstituted acetic acid derivatives served as penicillin biosynthetic precursors, one of the prime structural variations made feasible for the first time by partial synthesis was that of di-and trisubstitution at the a-position of the acyl substituent. All of the semisynthetic penicillins which have become important in medical practice are in fact disubstituted at the carbon a to the amide carbonyl. Such... 

Tolmetin sodium is a NSAID, which decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis. It is indicated in the treatment of chronic and acute rheumatoid arthritis and osteoarthritis and juvenile rheumatoid arthritis. Tolmetin and ketoroiac are structurally related heteroaryl acetic acid derivatives with different pharmacological features. Diclofenac is a phenylacetic acid derivative that was developed specifically as an antiinflammatory agent. 

Tolmetin and ketorolac are structurally related heteroaryl acetic acid derivatives with different pharmacological features. Diclofenac is a phenylacetic acid derivative that was developed specifically as an anti-inflammatory agent. 

Treatment of the < -arylhydrazono-3-thiazoline-2-acetic acid derivatives (141 R=H,Me,Et,6Bu,R1=H,Me,Ar=Ph,2,4,6-MegCgH2) with an alkali metal hydroxide (Lil/pyridine/DMF or lithiumpropane thiolate) effects rearrangement to the 2-aryl-6-thia-2,3,8-triazabicyclof3.2.1]-oct-3-en-4-carboxylates(142). An X-ray crystal structure showed the product (R=Me,R1=H,Ar=Ph) to exist as (142) in the solid. However, in solution an equilibrium between (142) and (143) occurs. Alkylation and acylation occur only through (143)1". A large number of mono-,di-,tri-,or tetraalkyl-A -thiazolines have been synthesised... 

The activity of several thiazolidine acetic acid derivatives of type (XLIII) against herpes virus in tissue culture has been reported [187] and structure activity relationships discussed [188], The most active of these compounds Me 1... 

Branched-chain sugar spirolactones 26 and 27, potential inhibitors of ATPase, have been derived in very high yields from isoxazolines 24 and 25, respectively by treatment with aqueous acetic acid. The structure of 26 was confirmed by X-ray crystallography (see also Chapters 10 and 21). 

Plant hormone biosynthesis and metabolism are influenced and modified, too, as already mentioned, by a large number of typical secondary plant constituents of quite different structures (Eef. 5, 6). For instance, it has been shown that some oi-disubstituted acetic acid derivatives are active both as antiauxins and as inhibitors of the biosynthesis of cyclic terpenoids. Thus, some more simple model compounds synthesized by ourselves, for example substituted a-phenoxy-isobutyrio acids, are not only competitive auxin inhibitors but they are also able to inhibit both the gibberellin and sterol biosynthesis. The same is true for some well known plant growth retardants, such as CCO or AMO 1618, which are inhibitors of gibberellin biosynthesis both in plants and in Fus ium moniliforme, but at the same time they are inhibiting and modifying also the biosynthesis of steroids in the respective organisms as well as in animal in vitro systems (Eef. 29) ... 

Amides such as 60 are viewed structurally as a combination of an amine and an acid, so there is an amine name and an acid name however, amides are treated differently than esters. For primary amides, an -NH2 group is attached to the carbonyl (two hydrogens on N see 60 Ri=R =H) the name of the acid is changed by replacing the oic acid with the word amide. Two examples in Table 16.3 are butanamide 67 and the ethanoic acid (acetic acid) derivative 68. Amide 67 is a butanoic acid derivative in which OH has been replaced by NH2 and the named is butanamide. The lUPAC name of 68 is ethanamide, but as a derivative of acetic acid, its common name of acetamide is used more often. 

---