Amides, Lactams

MeOH, 1%HCI, orl 9THF, 1% HCl, >52-85% yield/This group was used to protect a /3-lactam amide nitrogen during deprotonation of the a-position. 

P-Lactamases are enzymes that hydrolyze the P-lactam ring of P-lactamantibiotics (penicillins, cephalosporins, monobactams and carbapenems). They are the most common cause of P-lactam resistance. Most enzymes use a serine residue in the active site that attacks the P-lactam-amid carbonyl group. The covalently formed acylester is then hydrolyzed to reactivate the P-lacta-mase and liberates the inactivated antibiotic. Metallo P-lactamases use Zn(II) bound water for hydrolysis of the P-lactam bond. P-Lactamases constitute a heterogeneous group of enzymes with differences in molecular structures, in substrate preferences and in the genetic localizations of the encoding gene (Table 1). 

Mechansims of proton transfer have been studied for many compounds, including the reactions of acids with lactams, amides with various bases, and amines with alkoxide bases. ... 

Conversion of Formaldehyde into (V-Chloromethyl Lactams, Amides, and Ureas... 

Note that penicillins and structurally related antibiotics are frequently deactivated by the action of bacterial -lactamase enzymes. These enzymes also contain a serine residue in the active site, and this is the nucleophile that attacks and cleaves the P-lactam ring (see Box 7.20). The P-lactam (amide) linkage is hydrolysed, and then the inactivated penicillin derivative is released from the enzyme by further hydrolysis of the ester linkage, restoring the functional enzyme. The mode of action of these enzymes thus closely resembles that of the serine proteases there is further discussion in Box 7.20. 

In the model cAPK with bound staurosporine inhibitor, the lactam amide group of the inhibitor functions as a bidentate hydrogen bond donor-acceptor... 

Scheme 6 Basic saponification of the P-lactam amide in compound 17...

Alternative to the acid hydrolysis of the p-lactam amide system is the base promoted saponification reaction. Robinson and Pluschke [64] have employed the LiOH-promoted hydrolysis of the bicyclic p-lactam 17 as a means to the synthesis of key diamino acid residue 18, employed in the preparation of a malaria-vaccine candidate, Scheme 6. 

Trialkyloxonium ions have been extensively used to carry out O-alkylation of lactams, amides, sulfoxides, oxo-sulfonium ylides, iV-alkylation of iV-heterocycles, 5-alkylation of thioethers, thioacetals, thioamides, and thiolactams.1,90 Although trialkyloxonium ions do not alkylate benzene or toluene directly, alkylations readily occur in combination with highly ionizing superacids such as HS03F-SbF5. This may indicate protosolvation of a nonbonded electron pair on oxygen in the superacid medium. 

Baldwin and Christie (18) have proposed that the origin of this difference almost certainly derives from a stereoelectronic factor. In 64 and 65, the Cg - S bond is more nearly orthogonal to the B-lactam amide plane than the C — S bons is, with respect to the thiazolidine amide plane (cf. 66). The Cg - S bond is therefore weaker than the CA - S bond and is preferentially cleaved. With tricyclic a-lactam 61, due to the five-membered ring, the C - S bond becomes more nearly orthogonal to the thiazolidine amide plane (cf. 67). As a consequence, the ordering of bond lability is reversed and the C — S bond is cleaved more readily. The stereoelectronically controlled step 61 63 has led to a stereospecific synthesis of a penicillin derivative from a peptide precursor. 

Dithiophosphonsaure-anhydride sind hervorragend zur Ubertragung von Schwefel auf Ester, Lactame, Amide, Hydrazide, Ketone und ahnlichc Carbonyl-Verbindungen geeig-net668-671. 

A15.1.1.7 Amides and Lactams. Amides (R—CO—NR2 ) are fairly stable in water, but the amide bond is cleaved on heating in the presence of strong acid or bases. Nominally, this cleavage produces an amine and a carboxylic acid (R—CO—NR2 -1- H2O -1- strong acid or base R—CO—OH + HN— R2 )-An example here is acetaminophen, where it is hydrolyzed to form acetic acid plus p-aminophenol [7]. Amide hydrolysis is irreversible in acid because of protonation of the amine product. 

KHMDS in THF. The product 305 was isolated (45% yield, EfZ 75125) after deprotection of the /3-lactam amide group. 

The formation of polyamides by ring-opening polymerization of lactams can proceed through several types of reversible transacylation reactions in which the lactam amide bond is cleaved while a polymer amide bond is formed, viz. 

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