Enantioselective hydrolysis monoacetate

Irreversible Transesterification. A new preparation of chiral glycerol acetonide (2,2-dimethyl-l,3-dioxolane-4-methanol) involving an enantioselective hydrolysis of 2-0-benzylycerol diacetate to the (R)-monoacetate catalyzed by a lipoprotein lipase (47) has recently been developed. In an effort to prepare the (S)-enantiomer, we have used the aforementioned irreversible transesterification reaction using isopropenyl acetate as an acylating reagent, which upon reaction gives acetone as a... 

ENANTIOSELECTIVE HYDROLYSIS OF CiS-3,5-Dl ACETOXYCYCLOPENTENE (1 R,4S)-(+)-4-H YDROXY-2-CYCLOPENTENYL ACETATE (4-Cyclopentene-1,3-diol, monoacetate, (1R-c s)-)... 

Enantioselective hydrolysis catalyzed by lipase B from C. antarctica desymmetrized a meso diacetate to the chiral monoacetate. 

D. R. Deardorff, C.Q. Windham, C.L. Craney, Enantioselective hydrolysis of as-3,5-diacetox-ycyclopentene (lR,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate - (4-cyclopentene-l,3-diol, monoacetate, (IR-cis)-), Org. Synth. 73 (1996) 25-35. 

Tanake et al. [253] demonstrated the enzymatic synthesis of the sugar moiety of carbocyclic nucleosides required for the total synthesis of (-)-aristeromycin 150. Using lipase from Rhizopus delamar the enantioselective hydrolysis of mei o-l.S-bis(acetoxymethyl)-2-traw5 -alkylcyclopentane (151,152) was carried out to prepare the chiral monoacetate (153,154) in more than 96% e.e. (Fig. 53). The chiral monoacetate was also used in the synthesis of optically active 11-deoxyprostaglandins [254]. 

Diols such as the optically active 1,1 -binaphthyl-2-2 -diol (BINOL) have been used as versatile templates and chiral auxiliaries in catalysts employed successfully in asymmetric synthesis. The application of enzymes in the enantioselective access to axially dissymmetric compounds was first reported by Fujimoto and coworkers.83 In aqueous media, the asymmetric hydrolysis of the racemic binaphthyl dibutyrate (the ester) using whole cells from bacteria species afforded the (A)-diol with 96%ee and the unreacted substrate (A)-ester with 94% ee at 50 % conversion. Recently, in non-aqueous media, lipases from Pseudomonas cepacia and Ps. fluorescens have been employed in the enantioselective resolution and desymmetrization of racemic 6,6 -disubstituted BINOL derivatives using vinyl acetate.84 The monoacetate (K)-73 (product) was obtained in 32-44 % chemical yields and 78-96% ee depending on the derivatives used. The unreacted BINOL (S)-72 was obtained in 30-52 % chemical yield and 55-80% ee. 

Acetylcholine esterase-catalyzed hydrolyses have been reported only for a small number of prochiral diacetates (Table 11.1-8). However, several of secondary monoacetates, which are valuable synthetic building blocks, have been obtained with high enantioselectivity (2-6 and 11) by using this enzyme. Acetylcholine esterase should be considered for the hydrolysis of diacetates which are not substrates for lipases and pig liver esterase. 

Unsaturation in the alkyl chain frequently leads to the monoacetate of a higher ee value as exemplified with 16 and 17. Comparison of the enantioselectivities of the hydrolysis of diacetates to the corresponding monoacetates is often complicated by the lack of information on the amount of diol formed. The later arises from the hydrolysis of the monoacetate that may proceed under enantiomer differentiation, and thus the ee value of the monoacetate will be a composite of two enantioselective processes. Interestingly, upon changing the configuration of the double bond of the substituent R from ( ) to (Z) the enantiotopic group recognition by pig pancreas lipase inverts, as demonstrated by the monoacetates 8 and 9 as well as 11 and 12 (Table 11.1-10). 

A series of alkyl, alkoxy or acylamino 1,3-proanediol derivatives substituted in 2-position have been subjected to lipase-catalyzed acylation, and the monoacetates (1-12, 19, 20, 23-38, 40-42) were obtained with moderate to high enantiomeric excess (Table 11.1-17). For the monoacetates 1-12, reactions with and in ethyl acetate are usually slower than those with and in vinyl acetate. As in the hydrolysis of the corresponding diacetates, much higher selectivities were recorded with the yet unidentified carboxyl esterase from crude pig pancreas lipase. An excellent lipase for the enantioselective acylation of 3-benzyloxy-l,3-propane diol is Pseudomonas fluor-escens lipase, which gives high selectivity with vinyl acetate, isopropenyl acetate and ethyl acetate. By carrying the acylation further, to a certain extent to the diacetate, the enantiomerically pure monoacetate should be obtainable. 

Enzymatic hydrolysis of (la,2p,3a)-2-[(benzyloxy)methyl]-4-cyclopenten-l,3-diol diacetate has been demonstrated by Griffith and Danishefsky to obtain the corresponding monoester using acetylcholine esterase from electric eel [53,54]. We have described the enantioselective asymmetric hydrolysis of (la,2p,3a)-2-[(benzyloxy) methyl]-4-cyclopenten-l,3-diol diacetate 28 (Figiu-e 16.7) to the corresponding (h-)-monoacetate 29 by lipase PS-30 from Pseudomonas cepacia and pancreatin. A... 

In 1993, Overman achieved the first enantioselective total synthesis of (—)-strychnine using the optically pure monoacetate (+)-36, which was prepared by the enzymatic hydrolysis of 35 (70,71), as a starting material (Scheme 5). The key reaction in this synthesis is the cationic aza-Cope-Mannich rearrangement, which was previously developed by Overman et al. for the syntheses of various alkaloids, such as akuammicine (72-76), to assemble the CDE core ring system. The... 

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