Amides, 0-ketoSubject

Substituted malonates and (5-keto-esters have also been successfully used as pronucleophiles (Scheme 9.11) [25a, 36]. From P-ketoesters, approximately 1 1 mixtures of epimers are generally formed. Products derived from 2-alkenylmalo-nates have been subjected to Ru-catalyzed ring-closing metathesis to give cyclo-pentene derivatives in good yield [25a, 36]. With the ester-amide displayed in Scheme 9.11 as pronucleophile, 1 1 mixtures of epimers were also formed [44]. 

Treatment of a readily enolizable 1,3-dicarbonyl derivative with a mixture of diethylzinc and diiodomethane generates a 1,4-dicarbonyl by a chain extension process through the corresponding cyclopropanol derivative (equation 23) . Several enolizable starting materials such as / -ketophosphonates °, / -keto amides and amino acid skeletons have been subjected to these chain extension conditions. 

One problem of prime importance is the reliable determination of the number of residues of ,/3-unsaturated amino acids in proteins. Direct amino acid analysis subsequent to total hydrolysis of proteins is not feasible. The ,/3-unsaturated amino acids are subject to degradation with the formation of amide (ammonia) and -keto-acid. The numbers and types of ,/3-unsaturated amino acids in nisin (1) and subtilin (10) and in the fragments of the two peptides were, nevertheless, determined by amino acid analysis, only, however, after the addition of mercaptan across the double bonds of dehydroalanine and dehydrobutyrine (19). Using benzylmercaptan, the addition products are S-benzylcysteine (from dehydroalanine) and /3-methyl-S-benzylcysteine (from dehydrobutyrine). The two thioether amino acids are eluted from ion exchange columns of the amino acid analyzer free from interference by other amino acids... 

Azetidinone having a N-dehydroamino acid side chain, structurally related to the active penem and cephem antibiotics, was obtained by the standard phenylselenylation-oxidation-elimination reaction sequence [42], C-4-substituted aldehydes can also be subjected to a novel N- l-C-4 /S-lactam bond cleavage in the presence of 2-(trimethylsilyl)thiazole (TMST) to give enan-tiopure a-aUcoxy-y-keto amides (Scheme 12) as the major products [43]. 

Another approach for the total synthesis of anisomycin derivatives from (+)-tartaric acid has been reported via the N -benzyl tartarimide (95) (Scheme 11) [89]. Thus, (+)-tartaric acid was refluxed with benzyl amine in a xylene solution to give 95, which was subjected to reaction with the Grignard reagent of anisyl chloride in THF to give the keto-amide 96 in 55% yield. 

The synthesis of tetra-substituted ureas (1997JOC4155), amides (2000JOC8210), p-dicarbonyl compounds (2000JOC3679), and p-keto esters (2004JOC6617) are all examples of acylation by benzotriazolides and the subject of acylation at C-, N-, 0-, and S- centers has been thoroughly reviewed (2005SL1656). A few special examples follow, however, to illustrate the versatility of Bt methodology. 

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