Synthesis of p-lactams

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Taggi AE, Hafez AM, Wack H, Young B, Ferraris D, Lectka T (2002) The development of the first catalyzed reaction of ketenes and imines catalytic, asymmetric synthesis of P-lactams. J Am Chem Soc 124 6626-6635... 

Hodous BL, Fu GC (2002) Enantioselective Staudinger synthesis of P-lactams catalyzed by a planar-chiral nucleophile. J Am Chem Soc 124 1578-1579... 

Use of an interesting enamine photooxidation reaction has teen made of in the synthesis of P-lactams from 2-azetidine carboxylic esters (6.19) 625>. 

Ratcliffe, R.W. and Reuther, W., Total synthesis of P-lactam antibiotics. I. a-Thioformamidodiethylphosphonoacetates, Tetrahedron Lett., 4645, 1973. 

Synthesis of p-lactam antibiotics from sugars (either as chiral auxiliary or chiron), describing the general methodology developed in 1990s by Chmielewski and based on [2 + 2] cycloaddition of isothiocyanides to sugar olefins, was also comprehensively reviewed.5... 

Scheme 6 Covalent chiral auxiliary-induced asymmetric synthesis of p-lactams...

Bossio R, Marcos CP, Marcaccini S, Pepino R (1997) A facile synthesis of P-lactams based on isocyanide chemistry. Tetrahedron Lett 38 2519-2520... 

Reviews including aspects of P-lactam chemistry are ketene-imine cycloaddition reactions <98CHE1222>, radical cyclization processes <98MI169>, combinatorial synthesis <98AJC875>, electrophilic cyclization of unsaturated amides <98T13681> and theoretical studies on the synthesis of P-lactams <98MI245>. 

The asymmetric synthesis of P-lactames is still of interest to many organic and pharmaceutical chemists because of the great importance of these antibiotics. A detailed... 

The enzymatic synthesis of P-lactam antibiotics from P-lactam nuclei 6-aminope-nicillanic acid (APA) and 7-aminodeacetoxycephalosporanic acid (ADCA) and appropriate side chain donors has been largely studied [75, 76]. 

An efficient synthesis of P-lactam with D-phenylglycine or its derivatives as a side chain can be accomplished only by using a kinetically controlled approach via acyl group transfer from an activated side chain donor, and D-phenylglycine can be used as ester, usually methyl (PGM) or ethyl (PGE), or as amide (PGA). As a... 

Scheme 13 Asymmetric synthesis of P-lactams by chiral auxiliary based on D-xylose derivative...

Scheme 18 Bifunctional Lewis acid/nucleophile catalyzed synthesis of P-lactams...

Scheme 22 Stereoselective synthesis of P-lactams using Mukaiyama s salt...

Chiral imines derived from D-(+)-glucose have allowed an asymmetric synthesis of p-lactams by the [2+2] cycloaddition with ketenes [85]. c/A-p-Lac tarns were formed with very high diastereoselectivity and the stereochemistry at the C-3 and the C-4 was established as 3S and 4R from the known absolute configuration of the sugar moiety (Scheme 24). 

A comprehensive study on the solid-phase synthesis of p-lactam compounds has been reported [102]. In situ generated ketenes reacted with aldimines, immobilized on commercially available solid supports, under mild conditions to generate libraries of p-lactams in good to very good overall isolated yields. Different p-lactam derivatives with various substituents at the C-3 and the C-4 position... 

Scheme 49 Solid-phase synthesis of P-lactams via ester enolate-imine condensation...

The synthesis of p-lactams enantiomerically pure, via a multistep Gilman-Speeter type reaction [139] has been reported to be carried out with chiral oxazo-lidinones [140]. Titanium tetrachloride mediated condensation with imine gave an intermediate p-amino acyloxazolidinone, the major diastereomer of which could readily be purified by Si02 chromatography. Silylation and fluoride catalyzed cyclization gave the final p-lactam (Scheme 53). 

In 2007, Boyer and coworkers developed a complete study of the parameters that can influence the selective synthesis of p-lactam or p-aminoester during Refor-matsky reaction between ethyl bromodifluoroacetate and various imines. It clearly appeared that by modifying the nature of the amine or the reaction conditions, it was always possible to inverse the p-aminoester/p-lactam ratio (Scheme 55). 

Scheme 56 Regioselective synthesis of P-lactams by cobalt-catalyzed ring expansion of aziridines...

Scheme 75 Synthesis of P-lactam system by photorearrangement of isoxazolium anhydrobase...

Scheme 76 Synthesis of P-lactam-containing dipeptide analogs...

Scheme 82 Asymmetric synthesis of P-lactams by base-promoted cyclization of P-amino esters...

Scheme 83 Synthesis of P-lactams by bromo-enamides radical cyclization...

Scheme 87 Stereoselective synthesis of P-lactams from amino acid derivatives...

Scheme 99 Synthesis of P-lactam by P-amino acid cyclization...

Scheme 101 Catalytic synthesis of P-lactam fused enediynes...

Scheme 104 Regio- and stereoselective synthesis of P-lactams by cycloaddition reaction...

Bruggink A (2001) Synthesis of P-lactam antibiotics. Kluver, Dordecht (The Netherlands)... 

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