Sultams, hydrolysis

The excess acidity method has been used to show that some reactions do have pure A2 mechanisms, for instance the hydrolysis of some benzohydroxamic acids,126,211 the hydrolysis of sultams,212 and the oxidation of lactic acid in... 

The chiral auxiliary of alkylated A-acylbornane-10,2-sultams can be liberated by the use of hydroperoxide-assisted hydrolysis using lithium hydroxide/hydrogen peroxide9 in tetrahydro-furan/water (see Section 1.1.1.3.3.4.2.1.). This furnishes the chiral acids 2 in very high optical purities, along with the auxiliary which can be recycled. Other mild methods are available20. 

The reversible formation of a monoanionic trigonal bipyrimidal mtennediate with hypervalent sulfur (325) has been supported in the alkaline hydrolysis of the /J-sultam (326).297 A second deprotonation by hydroxide takes place to give (327) before the... 

Theoretical studies of the hydrolysis of lV-benzyl-3-oxo-/5-sultam (115) showed that the activation energies for the pathways leading to the products of C-N and S-N cleavage for the uncatalysed hydrolysis were very similar. However, when a second water molecule was involved, cleavage of the C-N bond was preferred.115 In a review, the mechanisms of reactions of /5-sultams have been compared with those of /3-lactams, including their reactions with some serine enzymes.91... 

Some tricyclic 1,3-thiazetidines of type (51) are reported (95CPB63). Selective C-S bond cleavage of 3-aryl-fS-sultams (52) with ethylaluminium dichloride gives aryl ketones or aldehydes by a process involving 1,2-aryl shift, imine formation and hydrolysis of the imine (95TL245). 

Table 8 Second-order rate constants for hydroxide ion hydrolysis of /3-sultam and /3-lactam analogues...

This alkaline hydrolysis shows a rate term that is second order in hydroxide ion concentration, which is indicative of a stepwise mechanism involving a TBPI with a hypervalent sulfur atom. Reversible attack of the hydroxide ion on a /3-sultam generates a monoanionic TBPI-, which requires deprotonation by a second hydroxide ion before the intermediate can collapse to products. 

However, an ElcB-type process was reported as a novel mechanism for hydrolysis of a /3-sultam. In the case of the N-a -methoxycarbon y I /3-sultam, deprotonation of the acidic exocyclic hydrogen leads to the formation of a carbanion, which then undergoes a rate-limiting conversion to a ring-opened species with expulsion of a sulfinate anion. Then, hydrolysis of the imine species produces benzoyl formate as the principal product detected (Scheme 14) <2002CC772>. 

Table 9 Second-order rate constants for the carboxylic acid-catalyzed hydrolysis of A/-benzyl /3-sultam...

Table 12 Second-order rate constants for the alkaline hydrolysis of /V-benzoyl /3-sultams...

Conversion of the isolated A-TBDMS carboxylic acid 111 to the active ester and reaction with amino acid esters yielded after desilylation the /3-sultam peptides 112 and 113. Removal of the protecting groups was also possible with benzylic esters but attempted hydrolysis of alkyl ester groups resulted in hydrolysis of the /3-sultam ring. Catalytic hydrogenation of the benzyl esters afforded the N-silylated /3-sultam peptides 114 in quantitative yields (Scheme 34) <2004M979>. 

Human neutrophil elastase (HNE) is a serine containing enzyme which is one of the most destructive of proteolytic enzymes, being able to catalyze the hydrolysis of the components of connective tissue. It has been implicated in the development of diseases such as emphysema, cystic fibrosis, and rheumatoid arthrisis. /3-Sultams are excellent candidates for exploring the mechanism of sulfonation and possible inhibition of serine protease enzymes. A-Benzoyl... 

Similar acryloyl imidazolidinones have been used in the asymmetric 1,4-addition of organomagnesium compounds in the presence of a Lewis acid. The diastereoselectivity is variable and was found to be highly depending on the nature of all the reaction participants.227 A symmetric fumaramide, obtained from the camphor-derived Oppolzer sultam, adds Grignard reagents, yielding after hydrolysis monosubstituted succinic acids with up to 90% ee (Scheme 73).228... 

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