Chiral monoacetates

Finally, prochiral bis(hydroxymethyl)phenylphosphine oxide 82 was desym-metrisized using either a lipase-catalysed acetylation (Method A) or hydrolysis of the corresponding diacetyl derivative 83 (Method B), to give the chiral monoacetate 84. Application of the two reverse procedures made it possible to obtain both enantiomerically enriched forms of 84 (Equation 40). ... 

The chiral monoacetates now available are useful multiple coupling reagents16-18 for syntheses of enantiomerically pure target molecules. They can be converted to nitroolefinic allylic esters, achiral or racemic analogues of which we have previously shown16-18 to combine sequentially with two (different) nucleophiles (see 1-2 in Scheme 1). 

Fig. 10 Enzyme-catalysed formation of chiral monoacetate synthons from meso-diacetate or meso-diol for chemo-enzymatic synthesis of monoterpenoid indole alkaloids...

The first enzymatic desymmetrizations of prochiral phosphine oxides was recently reported by Kielbasinski et al.88 Thus, the prochiral bis(methoxycarbonylmethyl)-phenylphosphine oxide 93 was subjected to the PLE-mediated hydrolysis in buffer affording the chiral monoacetate (RJ-94 in 72% ee and 92% chemical yield. In turn, the prochiral bis(hydroxymethyl)phenylphosphine oxide 95 was desymmetrized using either lipase-catalyzed acetylation of 95 with vinyl acetate as acyl donor in organic solvent or hydrolysis of 97 in phosphate buffer and solvent affording the chiral monoacetate 96 with up to 79% ee and 76% chemical yield. 

The asymmetric hydrolysis of (exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol, diacetate ester (37) to the corresponding chiral monoacetate ester (38) (Fig. 12B) has been demonstrated with lipases [61]. Lipase PS-30 from P. cepacia was most effective in asymmetric hydrolysis to obtain the desired enantiomer of monoacetate ester. The reaction yield of 75 M% and e.e. of >99% were obtained when the reaction was conducted in a biphasic system with 10% toluene at 5 g/liter of the substrate. Lipase PS-30 was immobilized on Accurel PP and the immobilized enzyme was reused (5 cycles) without loss of enzyme activity, productivity, or e.e. of product (38). The reaction process was scaled up to 80 liters (400 g of substrate) and monoacetate ester (38) was isolated in 80 M% yield with 99.3% e.e. The product was isolated in 99.5% chemical purity. The chiral monoacetate ester (38) was oxidized to its corresponding aldehyde and subsequently hydrolyzed to give chiral lactol (33) (Fig. 12B). The chiral lactol (33) obtained by this enzymatic process was used in chemoenzymatic synthesis of thromboxane A2 antagonist (35). 

A prochiral diol can be converted into enantiomeric compounds as shown by the example in Scheme 7.5. Catalyzed by a hydrolytic enzyme like a lipase, it can be enantioselectively acetylated by vinyl acetate in organic solvent to yield a mixture of monoacetates. The chiral monoacetates will be formed at unequal rates and also react further at unequal rates. It is usually anticipated that if kj > k2, then k4 > ky and, moreover, that the ratio ki/ki is constant throughout the reaction [4c],... 

Only a very few acyclic prochiral acylated diols have been subjected with moderate success to pig liver esterase-catalyzed hydrolysis with formation of the corresponding chiral monoacetates (1-3) (Table 11.1-4). For this kind of compounds, lipases are the hydrolases of choice. 

Chiral monoacetate esters 29 and 31 are key intermediates for total chemical synthesis of 32 (Baraclude), a potential drug for hepatitis B virus (HBV) infection [50-52]. Baraclude is a carboxylic analog of 2 -deoxyguanosine in which the furanose oxygen is replaced with an exocyclic double bond it was approved by the U.S. Food and Drug Administration (FDA) for treatment of HBV infection. 

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

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]. 

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