Lactones, hydrolysis transesterification

Recently, Maeda and coworkers utilized the (S, S) -le-catalyzed asymmetric alkylation of phenylglycine-derived Schiffbase 42 (R1 = Ph) for the stereoselective synthesis of a 4-hydroxy-2-phenylproline framework [27]. After hydrolysis and transesterification, the resulting (S)-49 was derivatized to its N-tosylate 50. Subsequent treatment of 50 with Br2 in CH2C12 resulted in the formation of y-lactone 51 with high diastereos-electivity this was then treated with NaH in methanol to give essentially pure (2 S,4R)-4-hydroxy-2-phenylproline derivative 52 in 80% yield from 50 (Scheme 5.25). 

The hydrolase-catalyzed reactions utilized most for the selective transformation of such substrates are hydrolysis (Schemes 11.1-1, 11.1-2, 11.1-4, 11.1-5 and 11.1-11), acylation (transesterification) (Schemes 11.1-3, 11.1-6 and 11.1-11) and alcoholysis (transesterification) (Schemes 11.1-7,11.1-8 and 11.1-15). Hydrolase-catalyzed esterification of an alcohol with a carboxylic acid, although highly useful in some casesl6Z, has been utilized to a lesser extent. Catalysis of formation and cleavage of the C-O bond of an ester or lactone by pig liver esterase, most lipases, a-chymotrypsin and subtilisin, which are all serine hydrolases, involves the following steps (Scheme... 

In 1982, Evans reported that the alkylation of oxazolidinone imides appeared to be superior to either oxazolines or prolinol amides from a practical standpoint, since they are significantly easier to cleave [83]. As shown in Scheme 3.17, enolate formation is at least 99% stereoselective for the Z(0)-enolate, which is chelated to the oxazolidinone carbonyl oxygen as shown. From this intermediate, approach of the electrophile is favored from the Si face to give the monoalkylated acyl oxazolidinone as shown. Table 3.6 lists several examples of this process. As can be seen from the last entry in the table, alkylation with unactivated alkyl halides is less efficient, and this low nucleophilicity is the primary weakness of this method. Following alkylation, the chiral auxiliary may be removed by lithium hydroxide or hydroperoxide hydrolysis [84], lithium benzyloxide transesterification, or LAH reduction [85]. Evans has used this methology in several total syntheses. One of the earliest was the Prelog-Djerassi lactone [86] and one of the more recent is ionomycin [87] (Figure 3.8). 

Each step of an isolation procedure requires confirmatory thin layer chromatographic (TLC) analysis to determine if isolation artifacts are produced (Fig. 3). Unwanted reactions include enzymatic and chemical hydrolysis during water extraction, esterification or lactonization of acidic saponins when using alcohol solvents, hydrolysis or transesterification of labile ester functions, and cyclopropane cleavage during acidic hydrolysis [10]. 

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