13- Lactam nitrogen

Cross-linked PVP can also be obtained by cross-linking the preformed polymer chemically (with persulfates, hydrazine, or peroxides) or with actinic radiation (63). This approach requires a source of free radicals capable of hydrogen abstraction from one or another of the labile hydrogens attached alpha to the pyrrohdone carbonyl or lactam nitrogen. The subsequently formed PVP radical can combine with another such radical to form a cross-link or undergo side reactions such as scission or cyclization (64,65), thus ... 

The Q and e values of VP are 0.088 and —1.62, respectively (125). This indicates resonance interaction of the double bond of the vinyl group with the electrons of the lactam nitrogen, whence the electronegative nature. With high e+ monomers such as maleic anhydride, VP forms alternating copolymers, much as expected (126). With other monomers between these Q and e extremes a wide variety of possibiHties exist. Table 14 Hsts reactivity ratios for important comonomers. 

The higher frequencies of the /3-lactam carbonyl absorption in fused systems has been attributed to increased inhibition of amide resonance as the /3-lactam ring becomes less planar (b-72mI50900 p. 303). For the 3-cephems (61) there is also the possibility of enamine resonance which could further reduce the ability of the /3-lactam nitrogen to contribute to amide resonance. 

The methoxy group on a /3-lactam nitrogen was cleaved by reduction with Li (EtNH2, r-BuOH, THF, —40°, 71 % yield). A benzyloxy group was stable to these cleavage conditions. ... 

The TBDMS derivative of a /3-lactam nitrogen is reported to be stable to lithium diisopropylamide, citric acid, Jones oxidation, and BH3-diisopropylamine, but not to Pb(OAc)4 oxidation. 

The benzyloxy group on a lactam nitrogen was cleaved by hydrogenolysis (H2, Pd-C) or by TiCl3 [MeOH, H2O, (NH4)2C03, Na2C03]. 

In addition to the intramolecular effects, steric factors are of considerable influence. The most usual one consists of steric hindrance to attack on the lactam nitrogen atom. Certain examples of this will be given. By comparison with uracil, it would be expected that uric acid (10) would be iV-methylated in the pyrimidine ring, but that in the imidazole ring 0-methylation should also be possible. However, the experiments of Biltz and Max show that all uric acid derivatives which carry a hydrogen atom in the 9-position are converted by ethereal diazomethane into l,3,7-trimethyl-8-methoxyxanthine (11). The following are examples uric acid and its 1-methyl, 3-methyl, 7-methyl, 1,3-dimethyl, 1,7-dimethyI, 3,7-dimethyl, and 1,3,7-trimethyl derivatives. Uric acid derivatives which arc substituted by alkyl groups in the 3- and 9-positions (e.g., 3,9-dimethyl-, 1,3,9-trimethyl-, and 3,7,9-trimethyl-uric acid)do not react at all with diazomethane, possibly because of insufficient acidity. Uric acids which are alkylated... 

DERIVATIVES OF DIBENZOLACTAMS A recurring theme in the present chapter has been the association of CNS activity with dibenzoheterocycles that bear a basic chain pendant from the central ring. As we have seen, considerable latitude exists as to the constitution of the central ring. The earlier volume in this series described the preparation of the antidepressant dibenzepin (90), in which the basic function is attached to a lactam nitrogen. 

The titanated bislactim ethers of cyclo(L-Val-Gly-) are added to nitroalkenes with high diastereo-selectivity (Eq. 4.60).SOa Michael addition of lactam bearing (S)-2-( 1-ethyl-1-methoxypropyl) pyrrolidine as auxiliary on the lactam nitrogen to nitroalkenes proceeds with high selectivity (de >96%, ee >96%).80b... 

The lactam 145, bearing a terminal triple bond, is transformed into the corresponding allene derivative 146 through a Crabbe reaction (Equation 7). Using Pd(PPh ()4 as the catalyst and in the presence of phenyl iodide, the corresponding indolizine is obtained. The lactam nitrogen atom is added to the central carbon atom of the allene... 

Penicillin and cephalosporin antibiotics are usually classed as P-lactam antibiotics, since their common feature is a lactam function in a four-membered ring, typically fused to another ring system. This second ring takes in the P-lactam nitrogen atom and also contains sulfur. In the case of penicillins, e.g. benzylpenicillin, the second ring is a thiazolidine, and in the cephalosporins, e.g. cephalosporin C, this ring is a dihydrothiazine. What is not readily apparent from these structures is that they are both modified tripeptides and their biosyntheses share a common tripeptide precursor. 

Moody and Rahimtoola reported a short synthesis of staurosporinone (293) without the use of protecting groups at the indole or the lactam nitrogen (761,762). This route involves an intramolecular Diels-Alder reaction of the pyrano[4,3- 7]indol-3-one 1325 and a subsequent cyclization by nitrene insertion. The pyrano[4,3-l7]indol-3-one 1325 was obtained in four steps from ethyl indol-2-yl... 

While a hydroxymethyl group has been succesfully used to temporarily block the lactam nitrogen of halopyridazin-3(2//)-ones such as 191 for Suzuki reactions <2003TL4459>, and the resulting aryl-2-hydroxymethylpyridazin-3(2//)-ones have been immediately deprotected in situ via a base-induced or thermal retro-ene reaction (Equation 39), two recent reports show that Suzuki reaction on unprotected substrates like 5-chloropyridazin-3(2//)-one 192 is feasible (Scheme 47) <2005JME6004, 2006JME2600>. 

Biotin (8.49), a thiophene-lactam, occurs in yeast, liver, kidney, eggs, vegetables, and nuts. It functions as a cocarboxylase in a number of biochemical reactions. It binds COj in the form of an unstable carbamic acid on one of the lactam nitrogens. The carbamate carboxyl is then donated easily. 

In contrast to the synthesis of bicyclic azetidinones containing a carboxyl group on the atom adjacent to the lactam nitrogen (see Section 5.12.3.4), few examples are reported in which bicyclic azetidinones without this carboxyl group are prepared from azetidinone precursors. One unique approach, however, utilized a free radical ring closure to obtain 6-oxa-l-azabicyclo[5.2.0]nonan-9-one (116) in modest yield (81TL2689). 

Lactam antibiotics are natural or semisynthetic compounds whose basic nuclear structure consists of a -lactam ring coupled to a thiazolidine (five-membered) or a dihydrothiazine (six-membered) ring to form the penicillin or cephalosporin nucleus, respectively. To those nuclei, various side chains that determine most of the properties of the different -lactams are attached. All members of this group of antibiotics are readily attacked at the -lactam nitrogen by nucleophilic reagents such as hydroxyl ions, alcohols, and primary amines, as well as by secondary amines. They are also susceptible to electrophilic attack at both the... 

Lactam Nitrogen Substitutions, Ring Opening Reactions. 174... 

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