1- Azetidinone acetic acid

CjjHjoOioSi 115437-18-8) see Paclitaxel [(triethylsilyl)oxy]acetic acid ethyl ester (C oH220jSi) see Paclitaxel c -3-(triethylsilyloxy)-4-phenyl-2-azetidinone (Ci3H23N02Si) see Paclitaxel trifluoroacetic anhydride... 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

The synthesis of tazobactam from 6-APA (Scheme 6.15) proceeded via the 2- -(chloromethyl)penam ester (81 a), which was first prepared by Gottstein and co-workers [47] during the synthesis of 2-/S-(chloromethyl)-2-a-methylpenam-3a-carboxylic acid 1,1-dioxide (29). 6-APA (8) was converted to 6a-bromopenicillanic acid (77) by treatment with sodium nitrite and hydrobromic acid. Oxidation with peracetic acid in the presence of benzophenone hydrazone gave benzhydryl 6a-bromopenicillanate-l-oxide (78) and reduction with zinc and acetic acid gave benzhydryl penicillanate-1-oxide (79). The unsymmetrical azetidinone disulphide (80) was obtained by heating with 2-mercaptobenzothiazole reaction with copper (II) chloride... 

Many examples of the usual route to /S-lactams via imines and acid chlorides, ketens, or keten equivalents have appeared.These include syntheses of 3-[bis(alkylthio)methylenamino]-2-azetidinones, ° of spiro-azetidinones and bis-azetidinones, and the use of l-methyl-2-halogenopyridinium salts to activate carboxylic acids towards coupling with imines. A non-hazardous alternative route to 3-amido-2-azetidinones, avoiding the use of azidoacetyl chloride, involves the reaction of Schiff bases with salts of [(a-methyl-/3-methoxycar-bonyl)vinylamino]acetic acid, e.g. (20), in the presence of ethyl chloroformate, as shown in Scheme 5. Formaldimines can be generated from their trimers by treatment with Lewis acids immediately prior to reaction with acid chlorides, so allowing the formation of the nocardicin nucleus which is unsubstituted at C-4. ... 

Ha and Hart [78] introduced a new functional group conversion of the 4-styryl group in azetidinones of type 142 (Scheme 24). Namely, the trans isomer of 142, readily available from the lithium enolate 147 and the imine 141, was iV-deprotected and the resulting N-H azetidinone converted to the bromohy-drin 148. Dehalogenation and further Jones oxidation of the resulting diastereomeric alcohols 149 produced the ketone 150, which was transformed into the 4-acetic acid derivative 151 by Baeyer-Villiger oxidation. 

The penem system has always been assembled by late formation of the thiazoline ring. No attempt to obtain penems by closing the azetidinone ring as the last step has ever been reported, though this strategy is well documented on penicillins [3, 4]. Approaches based either on the dehydrative condensation of thiazoline acetic acids 4 or on ketene addition to thiazoles 5, reactions known to... 

The existence of an equilibrium between penicillin sulfoxide and the azetidinone sulfenic acid was first explored in 1969 and further substantiated by several groups (Cooper and Spry, 1972). The intermediate, however, had never itself been isolated. Indeed, an isolable sulfenic acid was a rare entity. Chou and co-workers (1974) observed that a mixture was obtained after an ethyl acetate solution of the sulfoxide (17) was refluxed and rapidly cooled. Separation, by fractional crystallization, yielded the starting sulfoxide (17) and a second compound identified as the sulfenic acid (19). Cyclization of 19 to the sulfoxide occurred readily (/1/2 3 hr at 38°C in chloroform). NMR data indicated that the structure of the sulfenic acid was best represented by isomer a rather than iso mer b. 

Appropriately substituted hydroxy amides and ureas can be used instead of diamines. Thus, acid-catalyzed cyclocondensation of iV-carbamoyl prolinols 137 (R1 = H, (CH2)3) (Scheme 27) with aldehydes RCHO (R = Ph, 2-MeOC6H4, 2-naphthyl, etc.) stereoselectively afforded a series of pyrroldine-fused oxadiazepinones 46 (Scheme 5) <1990CPB2627, 1990H(30)287, 1996LA927>. Similar heterocyclization of 4-(2-hydroxyethylthio)-2-azetidinone with acetone dimethyl acetal was used in the synthesis of azetidinone-fused oxathiazepanes of type 33 (X = S) (Figure 4) <1980JA2039>. 

The silver acetate-promoted 1,3-dipolar cycloaddition of nitrilimines with 3(/f )-pheny]-4(A )-cinnamoyl-2-azetidinone produced the major adduct, 4-(4,5-dihydro- (g) pyrazol-5-yl)carbonyl-2-azetidinones, with high stereoselectivity.70 The 1,3-dipolar cycloadditions of substituted 2,7-dime(liyl-3-thioxo-3,4,5,6-ici.rahydro-2//- 1,2,41 triazepin-5-one with iV-aryl-C-ethoxycarbonylnitrilimines are highly chemoselective, where the sulfur atom of the dipolarophile interacts with the carbon atom of the dipole.71 The enantioselective 1,3-dipolar cycloaddition of nitrile imines with electron deficient acceptors produces dihydropyrazoles in the presence of 10 mol% of chiral Lewis acid catalyst.72... 

Some reactions of munchnones occur via acylamino ketenes, the covalent valence tautomers of the betaines. The ketenes are intermediates in the thermolysis (see Scheme 22) and in the formation of azetidinones from imines (equation 69) they are thought to be involved in the aminolysis of the mesoionic compounds, which results in amides of a-acylamino acids, and in the formation of the benzodioxin (247) by the combined action of acetic anhydride and tetrachloro-o-benzoquinone on Af-benzoylalanine (equation 70). 

---