5-lactone base pairing

All of the hydroxyacid metabolites also exist in their corresponding inactive lactone forms. After base hydrolysis to convert lactones to active inhibitors, about 80% of the total enzyme inhibitory activity in human plasma is accounted for by these four lactone/hydroxyacid pairs. 

Abbreviations used in this chapter bp, base pairs FAD, flavine adenine dinucleotide GLO, L-gulono-y-lactone oxidase ODS rat, osteogenic disorder Shionogi rat UDPGT, uridine diphosphate glucuronosyl-transferase. 

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

It should be pointed out that capillary GC is more suitable for the separation of some volatile enantiomers in a complex matrix, such as essential oils, where high peak capacity and hence high column efficiency is required [69, 70]. Approximately 50 components including enantionmers in the natural peppermint oil were separated using a GC method [70]. Eight pairs of volatile lactone emantiomers were resolved by GC with a y-cyclodextrin-based column [71]. 

The Michael addition of nucleophiles to coumarins catalyzed by solid bases provides an interesting approach to the synthesis of 4-substituted 3,4-dihydrocumarins, because with the conventional Michael catalysts the alkaline hydrolysis of the 8-lactone predominates (Scheme 44). Results were obtained when the Michael addition of diethyl malonate to coumarin was catalyzed by the activated Ba(OH)2 292). An unusual 1,2-addition-elimination process at the C = 0 bond was observed. The mechanism of this reaction was explained on the basis of the microcrystalline structure of the catalyst. It was suggested that the rigid coumarin molecule interacts with the Ba ions through the lone-pair electrons of both oxygen atoms of the... 

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