3-Amino-p-lactams

Monosubstituted-5(4//)-oxazolones behave differently upon reaction with imines. Here, 4-methyl-2-phenyl-5(4/7)-oxazolone 196 (Ri = Ph, R2 = Me) reacts with imines derived from 2-furancarboxaldehyde or 2-thiophenecarboxaldehyde to give 3-amino-p-lactams 197. On the other hand, 196 reacts with chlorosul-fonyl isocyanate in a [2 + 2] cycloaddition to give dioxazabicycloheptanones 198 as shown in Scheme 7.60. ... 

P-lactams from Arnstein tripeptide derivatives had not yet been carried out (Fig. 40). The intramolecular Pummerer-type cyclization of the closely related (fi)-Am-stein tripeptide analogues with SKA predominantly gave the cw-P-lactams and the (S)-Arnstein tripeptide analogues gave a mixture of cis and trans P-lactams.59a It is noteworthy that cw-P-lactams were preferentially obtained from the (/ )-substrate considering the fact that the 3-amino-P-lactam moiety of naturally occurring... 

Significant progress has been made in the development of asymmetric syntheses of the biologically important 3-amino-p-lactams from homochiral ketene precursors.High levels of diastereoselection have been observed with chiral 1,3-oxazolidinones. Thus (4/ )-phenyloxazolidylacetyl chloride, readily prepared from (S)-phenylglycine, reacts with N-benzylaldimines in the presence of tri-ethylamine to yield die cis 3-lactams in high diastereoisomeric excesses (Scheme IS). ... 

Lactams. This N-(cyanomethyl)amine reacts with lithium ester enolates to afford 4-unsubstituted p-lactams in 60-75% yield (equation I). This reaction is generally applicable to N-(cyanomethyl)amines. 3-Amino-p-lactams can be ob-... 

Van Koten and coworkers prepared zinc ester enolates of IV-protected a-amino esters from the corresponding lithium enolates and allowed them to react with imines at low temperature to obtain trans-3-amino-P-lactams, often with high stereoselectivity as shown in Scheme 19. Interestingly, the authors interpreted their results in terms of an internally chelated zinc-oxygen bonded enolate (37). 

The synthesis of monocyclic 3-amino-P-lactams by the photolytic reaction of imines with pentacarbonyl[(dibenzylamino)carbene]chromium(0) was developed by Hegedus and co-workers [74]. These reactions are closely related to the previously described [2 -h 2]-cycloaddition reactions in that they are thought to involve attack of the imine nitrogen on a photogenerated, metal-bound ketene, followed by ring closure (Scheme 15). In a synthesis of a nocardicin precursor, optically active imine trimer 122 was photolyzed with carbene complex 123 providing a 46% yield of a 1 1 diastereomeric mixture of lactams... 

Compound 136 can be transformed to the 3,4-trans isomer 138, which has the same configuration as ( + ) thienamycin, according to the procedure described by Chiba and coworkers in related structures [74]. The method involved oxidation of the hydroxyl group in 136 with activated manganese dioxide with concomitant isomerization at C-3, followed by K-selectride reduction of the resulting methyl ketone 137. Zinc enolates of iV,iV-disubstituted a-aminoacid esters have also been recently utilized for the synthesis of 3-amino P-lactams [75]. 

Asymmetric synthesis of 3-amino p-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

Chiral ketene fragments have proven to offer more general utility in the quest for enantioselective Staudinger reactions. In particular, ketenes containing the Evans oxazolidinone have proven to offer high diastereoselectivities in the synthesis of 3-amino-P-lactams. The ease of preparation of the carboxylic acid precursor, the low cost of the auxiliary, and the facile unmasking of the 3-amino group from the auxiliary all... 

The synthesis and biological evaluation of various p-lactams as anticancer agents have been demonstrated by Banik et al. [28]. The anticancer activities of these compounds have prompted them to study the synthesis of pyrroles bound to the P-lactams 4 and 5. They identified an expeditious synthetic method for the preparation of pyrroles fused with p-lactams by the reaction of 3-amino p-lactams with acetonylacetone in the presence of catalytic amounts (5 mol%) of molecular iodine at room temperature (Scheme 10.3). 

CO)sCr=CHNBzli- (cf. 11, 400-401). This carbene, like typical Fischer carbenes, undergoes a photolytic addition to imines to give mixtures of cis- and trans-3-dibenzylamino-p-lactams in fair to good yield. The products are convertible into 3-amino-2-azetidinones.1 2 4 5... 

Ring opening of p-lactams at C2-C3 with application in peptide synthesis was first reported on a-keto p-lactams 126 ([116] for applications of a-keto p-lactams, see [117]), Scheme 42. These p-lactams, readily available via oxidation of 3-hydroxy p-lactams 125, undergoes a Baeyer-Villiger reaction upon exposure to m-CPBA and affords /V-carboxy a-amino acid anhydrides (NCAs) 127 [118]. Shortly after, it was discovered that a more direct, one pot route to these NCAs is feasible by treatment of 3-hydroxy p-lactams with a solution of commercial bleach... 

Optically active p-lactones are readily prepared by ketene-aldehyde cycloaddition using 72 as the chirality inducer.The products are excellent precursors of p-amino acids. The [2 + 2]cycloaddition of ketenes and imines in the presence of 0-benzoylqui-nine leads to numerous ciT-2,3-disubstituted p-lactams. ... 

A mixture of diastereomeric azides EjZ) in fast equilibrium (III, Fig. 19) has been obtained by treatment of 3-alkenyl-3-bromoazetidin-2-ones with NaNs [291]. The subsequent hydrogenation and the following protection with CBz derivatives afforded 3-(2 -amino)-p-lactams as single diastereomers (IV, Fig. 19). 

The use of iV-trialkylsilylimines can be advantageous, since the protecting A -substituent can easily be cleaved from the f amino acid esters produced. The reaction of mono- or disubstituted ketene silyl acetals with A -trimethylsilyl-benzylideneamine in the presence of 10 mol% of 1 gives the corresponding P-amino acid esters in good yield (eq 3) (5). p-Lactams have also been synthesized in moderate yield by in situ treatment of the intermediate with MeMgBr(eq 3) (J). 

The selective acid-induced removal of sulfinyl protecting group from the N-sulfinyl-l -amino-dioxolan-4-ones 91 provided the corresponding 1 -aminodioxolan-4-ones 92 (Scheme 3.34) [69]. The base-induced cychzation in the unprotected dioxolan-4-one 92 has been reported to afford the corresponding chiral tetrasubstituted 3-hydroxy-p-lactams 93 in good yields and excellent diastereoselectivity. 

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