Lactams spirocyclic

Raghunathan has disclosed a synthesis of spiropyrrolidines 143 based on the Grigg triethylamine protocol (Scheme 2.38).64 The structurally complex spirocycles are formed in a single step, in high yield from simple starting materials. This protocol was extended to the synthesis of (3-lactam spirocyclic compounds.65... 

In a related reaction, treatment of spirocyclic oxaziridines with MnCl(TPP), where TPP = m o-tetraphenylporphyrinate (2 — ), or photolysis leads to a lactam. 

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). 

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

Novel Aspects on the Preparation of Spirocyclic and Fused Unusual p-Lactams... 

Keywords p-Lactams Cycloadditions Fused-rings Metals Spirocycles... 

Preparation of Spirocyclic-P-Lactams with Nonclassical Structure. 4... 

In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition [15-21] to gene activation [22], Systems containing one carbon atom common to two rings, spirocyclic compounds, represent an important structural organization. Spirocyclic p-lactams (Fig. 3) behave as p-tum mimetics [23-26] as well as enzyme inhibitors [27, 28], they are precursors of a,a-disubstituted p-amino acids [29-32], and the spiranic p-lactam moiety is present in chartellines and chartelamides [33-38], a family of marine natural products. Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described [38],... 

Scheme 1 Preparation of spirocyclic P-lactams through Staudinger reaction...

---