Lactams stereoselective synthesis

The stereoselective synthesis of classical trinems (fused tricyclic systems having the azetidin-2-one nucleus fused through the N-C4 bond) <98MI347> and the chemistry of non-classical polycyclic P-lactams have been reviewed <00T5743>. 

A highly stereoselective synthesis of ( )-deplancheine has been developed (121), utilizing a photocyclization process for the preparation of enelactam 181, which was reduced by zinc in acetic acid to lactam 182. In the latter, the double bond was shifted to the 19,20 position stereoselectively with an E geometry by the use of nonacarbonyldiiron catalyst to supply 159, previously synthesized and transformed to ( )-7 by Winterfeldt et al. (112). 

Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim S-H, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FYF, Long BH, Vite GD. (2000) A novel application of a pd(0)-catalyzed nucleophilic substitution reaction to the regio- and stereoselective synthesis of lactam analogues of the epothilone natural products. J Am Chem Soc 122 8890-8897. 

Since the migrating group retains its configuration, the use of enantiomerically enriched oximes provides a direct entry to enantiomerically pure lactams. These lactams may be used as a key building block for the synthesis of diverse compounds. Westermann and Gedrath applied this strategy to the stereoselective synthesis of enantiomerically pure o-.a-disubstituted a-amino acids (equation 135), bicyclic lactams and the spirocyclic framework of Histrionicotoxins (equation 136). 

This article aims to review the development in stereoselective synthesis of spiro-(5-lactams and their biological evaluation as well as applications in various fields. 

Scheme 36 Stereoselective synthesis of Ai-phenylsulfonyl-spiro-(3-lactams...

These results prompted them to attempt the stereoselective synthesis of the IV-phenylsulfonyl substituted spiro- (3-lactams 150, 151 (Scheme 36) from the N-(phenylmethyIe ne )be n ze nesulfonamide and the ketene valence tautomer of the bicyclic mesoionic compounds such as (2 S,4/ )-4-acetyloxy or benzoyloxy-IV-acyl-prolines 149 in the presence of acetic anhydride [109]. The presence of the stereocenter in position 4 of the cyclic amino acid 149 was found to be sufficient to ensure complete stereoselectivity on the spiranic C-4. 

In connection with these results, and as an extension of their studies toward the reactivity of new bicyclic mesoionic compounds and their usefulness in the synthesis of condensed heterocycles, they further reported the stereoselective synthesis of spiro-(3-lactams 153, 154 (Scheme 36) by reactions of imines with mesoionic compounds or ketenes generated from A-acyl-thiozolidine-2-carboxylic acids 152 [110]. 

Scheme 51 Stereoselective synthesis of spiro-(3-lactams using D-(+)-glucose derived chiral ketenes...

Deshmukh et al. [134] have investigated the use of D-(+)-glucose derived chiral ketenes in the stereoselective synthesis of spiro-(3-lactams 226-227. The D-(+)-glucose acid chloride 224, serving as a ketene precursor, in the Staudinger cycloaddition reaction with appropriate imines 225 afforded the diastereomeric mixture of spirocyclic-(3-lactams 226-227 in 70 30 ratio, respectively. This reaction has cleanly produced only two diastereoisomers instead of theoretically possible four... 

In conclusion, the CAI activity of spiro-(3-lactams, their antiviral and antibacterial properties, their potential as efficient (3-tum nucleators and (3-tum mimetics, and their application as synthons for a,a-disubstituted (3-amino acids motivated synthetic and medicinal chemists to design novel spirocyclic (3-lactams. Several approaches to the stereoselective synthesis of spiro-(3-lactams have been described in this review. However, ketene-imine cycloaddition (Staudinger Reaction) shows much versatility for the access to diversely functionalized spiro-(3-lactams. In addition, we have developed a facile route to novel spiro-(3-lactams by using... 

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

The stereoselective synthesis of bis-(3-lactams grafted macrocycles has been described [109]. Macrocyclic imine and phenoxy acetyl chloride in the presence of triethylamine produced a diastereomeric mixture of cis macrocyclic bis-(3-lac-tams (Scheme 36) by the Staudinger reaction. 

Scheme 52 Stereoselective synthesis of (3-lactam inhibitor of the serine protease prostate-specific antigen...

Scheme 70 Stereoselective synthesis of (3-lactams by photochemical rearrangement...

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

A new protocol for the stereoselective synthesis of (i-lactams [213] has been reported to be performed by a conrotatory ring closure of l-halo-3-aza-4-alkyl-l, 3-dienes, previously prepared by Staudinger methodology, (for the synthesis and chemistry of /V-silyl imines see [214] for [2+2] cycloaddition of /V-silyl imines and ketenes see [215]) in refluxing toluene (Scheme 96). 

Scheme 96 Stereoselective synthesis of 3-unsubstituted P-lactams by conrotatory ring closure of 1,3-diene derivatives...

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

Scheme 110 c -Stereoselective synthesis of [S-lactams by catalytic systems... 

Moreover, using the same starting materials, they have reported the regio- and stereoselective synthesis of enantiopure or racemic benzofused tricyclic (3-lactams such as benzocarbapenems and benzocarbacephems (III and IV, Fig. 17) via intramolecular aryl radical cyclization [287]. 

The same authors have also investigated the stereoselective synthesis of unsym-metrically disubstituted azetidin-2-ones (V, Fig. 21) by using Lewis acid mediated functionalization of (3-lactams with various active aromatic substrates [298],... 

In the present review the ring systems containing one heteroatom are considered first, except for P-lactams which are given a special section at the end. Interest in azetidines continues to be stimulated by the discovery of the potentially useful trinitro derivative. The requirements for the stereoselective synthesis of substituted oxetane are being explored and derivatives of aluminium are useful in the stereoselective routes to oxetanones. The preparation and subsequent pyrolysis of oxetanones is suggested as an alternative to the Wittig route to olefins. Stereoselective routes to thietanes and thietane 1 -oxides are mentioned. 

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