Lactam 3-lactone

Silylketenes in formation of (3-lactones and (3-lactams 98JCS(P1)2105. Syntheses of (3-lactams, (3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

Gilley CB, Kobayashi Y (2008) 2-nitrophenyl isocyanide as a versatile convertible isocyanide rapid access to a fused y-lactam (3-lactone bicycle. J Org Chem 73 4198 204 Chen JJ, Golebiowski A, Klopfenstein SR, West L (2002) The universal Rink-isonitrile resin applications in Ugi reactions. Tetrahedron Lett 43 4083 085 Hulme C, Peng J, Morton G, Salvino JM, Herpin T, Labaudiniere R (1998) Novel safety-catch linker and its application with a Ugi/De-BOC/Cyclization (UDC) strategy to access carboxylic acids, 1, 4-benzodiazepines, diketopiperazines, ketopiperazines and dihydroqui-noxalinones. Tetrahedron Lett 39 7227-7230... 

Elucidation of the role of the 205 proteasome in protein degradation and as a target for cancer chemotherapy could not have been achieved without small molecule inhibitors, some of which have served strictly as research tools, while others have progressed through preclinical development and clinical trials.18,28,29 These molecules represent a variety of structural classes, including peptide boronic acids such as bortezomib and CEP-187 70,30 epoxyketones (e.g. carfilzomib)31 and the y-lactam-(3-lactone family of inhibitors (Figure 12.1). 

The structure of NPI-0052 offered unique substitutions about the y-lactam-(3-lactone ring system with functional groups that significantly enhanced its potency and potential for drug development, as highlighted in this account. 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Heterocyclic Compounds (see also Anhydrides, Aziridines, Epoxides, Episulfides, Imides, Lactams, Lactones)... 

Macrocyclic 14-membered lactams, lactones, and thiolactones 211 have also been prepared from 3-amino-l,2,5-thiadiazole-4-carboxylic acids 210 (Equation 47) <1996CHE975>. 

Intramolecular C-H insertion reactions of metal carbenoids have been widely used for the stereoselective construction of substituted lactams, lactones, cyclopentanones, benzofurans, and benzopyrans. Several excellent reviews have been published covering the general aspects of intramolecular C-H insertion by metal carbenoids.46,47 62 71 99-104 The following section highlights the major advances made since 1994, especially in asymmetric intramolecular C-H insertion. 

A particular mechanism of barbiturate ring opening has been observed for some barbiturates hydroxylated on the side-chain. The mechanism and relevance of this tautomeric lactam-lactone equilibrium are discussed in Chapt. 11. 

The most common cyclization reactions in drug metabolism proceed with elimination of a H20 molecule. These reactions produce lactams, lactones, cyclic Schiff bases, and even more-complex metabolites. 

The two antimigraine drugs proxibarbal and valofan (11.153 and 11.154, respectively, Fig. 11.19,a) attain lactam-lactone equilibrium, the mechanism of which is summarized in Fig. 11.19,b. In aqueous media, the proxibar-bal/valofan ratio increased linearly with pH, from 78 22 at pH 6.75 to 84 16 at pH 7.4. As for the two diastereoisomers of valofan, their cis/trans ratio remained constant and close to 63 37 in the pH range of 6-9 [164],... 

The range of monomers that can be incorporated into block copolymers by the living anionic route includes not only the carbon-carbon double-bond monomers susceptible to anionic polymerization but also certain cyclic monomers, such as ethylene oxide, propylene sulfide, lactams, lactones, and cyclic siloxanes (Chap. 7). Thus one can synthesize block copolymers involving each of the two types of monomers. Some of these combinations require an appropriate adjustment of the propagating center prior to the addition of the cyclic monomer. For example, carbanions from monomers such as styrene or methyl methacrylate are not sufficiently nucleophilic to polymerize lactones. The block copolymer with a lactone can be synthesized if one adds a small amount of ethylene oxide to the living polystyryl system to convert propagating centers to alkoxide ions prior to adding the lactone monomer. 

Copolymerizations between pairs of cyclic esters, acetals, sulfides, siloxanes, alkenes, lactams, lactones, /V-carboxy-a-amino acid anhydrides, imines, and other cyclic monomers... 

Other examples are acetoacetates alkylamines and alkylhalides/acid halides ethers esters chloroformates ketones lactames lactones malonates mercaptanes and orthoesters in aliphatics catechol/hydroquinone/resorcinol, cresidines haloaromatics in aromatics and coumarines, cyanuric chloride, picolines, quinolines, and thiazoles in heterocylics. 

Several complexes with ligands related to amides, such as lactams, lactones and antipyrine (atp) have also been recorded (Table 77) apart from preparative and IR spectroscopic information, little is known about them. The precipitation of U02(NCS)2-3atp from aqueous acid in the presence of thiocyanate has been used as a method for the determination of uranium in minerals. 

Table 77 Some Complexes of Lactams, Lactones and Antipyrine (atp) with Dioxouranium(Vl) Compounds...

When the basic center is exocyclic, as in lactams, lactones, etc., the results can be interpreted in a straightforward way analogous to the argument given previously (Chapter 5) for biphenylene. Consider the series of lactams ... 

Heterocyclic compounds (see also Aziri-dines, Epoxides, Lactams, Lactones) Three-membered heterocycles (excluding epoxides and aziridines) Acetone-Potassium peroxomonosul-fate, 120... 

The applications of re-acidic chiral stationary phases include the resolution of a-blockers and /1-blockers, amines, arylacetamine, alkylcarbinols, hydantoins, barbiturates, naphthols, benzodiazapines, carboxylic acids, lactams, lactones, phthaldehydes selenoids, and phosphorus compounds. Hyun et al. [16] achieved a chiral resolution of a homologous series of iV-acyl-x-(l-naphthyl )cthylaminc on AA(3,5-dinitrobenzoyl-(i )-phenylglycine and N-(3,5 - dini tr o ben zoy I)-(,S ) -1 c u c ine CSPs. The authors used hexane-2-propanol (80 20, v/v) as the mobile phase. Similarly, the scope of re-basic CSPs comprises the chiral resolution of / -blockers, amino acids, amines, diamines, amino phosphonates, naphthols, benza-diazapines, carboxylic acids, hydroxy acids, dipeptides, tripeptides, diols,... 

Using the phthalimide/methylthioether-pair, a variety of photochemical transformations resulting in medium- and macrocyclic sulfur containing amines, lactams, lactones, and crownether analogues, respectively, with a maximum ring-size of 38 atoms have been described [26,27]. Scheme 10 summarizes some selected examples. 

Griesbeck et al. have developed the decarboxylative photocyclization (PDC) of phthalimido oo-alkylcarboxylates (15) as a versatile route to macrocyclic ring systems (16). The carboxylate serves as electron donor and C02 is eliminated during the course of the reaction. Applying this concept, the syntheses of medium- and macrocyclic amines, polyethers, lactams, lactones, as well as cycloalkynes were accessible but the limitations... 

The Ym vs. Nch2 curves belong to two types, similar but different. The first type, Fig. 6.7a, is identical in curvature for all polymer families containing only one functional group per repeating unit poly-oxides, -sulphides, -carbonates, -lactams, -lactones and -sulphones belong to this type. 

These methods parallel the syntheses just described for the five-membered rings. As indicated in structures 5158, standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans, and tetrahydrothiopyrans (53 Z = N, O, S) glutarimides, glutaric anhydrides, and glutaric thioanhydrides (55 Z = N, O, S) and -lactams, -lactones, and -thiolactones (58 Z = N, O, S) (Scheme 37). 

Some heterocycles have both nucleophilic and electrophilic atoms in their molecule. Thus they can be opened and polymerized by the anionic, cationic or coordination mechanisms. Examples are lactams, lactones, and cyclic siloxanes. Investigations of the mechanism of lactam propagation are complicated by the occurence of side reactions. In principle, the mechanism described in Chap. 3 by the schemes (55)—(57) and (71) is accepted. Anionic polymerization of cyclic esters consists, in most cases (see Chap. 4, Sect. 2.2) of repeated reversible attacks on the carbonyl carbon by the anion 0]-. From e-caprolactone, polyester chains grow according to [315]... 

In general, ketones are preferentially attacked by hydrazoic acid when both ketonic and carboxylic groups are present in the same molecule (c/. conversion of 152 to 153 in Scheme 28). Thus, treatment of the ketophenolic acid (159) with sodium azide in phosphoric acid chemo- and regio-selectively gives the lactam-lactone (160) as the sole product (equation 47). "... 

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