Methoxyacetate Esters

Carbonates are less reactive than esters towards basic hydrolysis owing to the reduced electrophilicity of the carbonyl afforded by the resonance deactivation by two oxygens. However, hydrolytic methods confer little advantage to carbonates as protecting groups and in general, the conditions that would attack esters may also attack carbonates. 

7 The Biocatalytic Approach to the Preparation of Enantiomerically Pure Chiral Building Blocks. Santaniello, E. Ferraboschi, P. Grisenti, P. Manzochi, A. Chem. Rev. 1992. 92, 1071. 

9 Enzymic Method in Preparative Carbohydrate Chemistry. David. S Aug. C Gautheron, C. Adv. Carbohydr. Chem. Biochem, 1991, 49, 176. 

10 Applications of Pig Liver Esterases in Asymmetric Synthesis. Zhu, L.-M. Tedford. M. C. Tetrahedron 1990, 46, 6587. 

11 Asymmetric Transformations Catalysed by Enzymes in Organic Solvents. Kli-banov, A. M. Acc. Chem. Res 1990. 2J, 114. 

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The lability of esters can be easily enhanced by substituting the a-position with electron-withdrawing groups. Thus, methoxyacetate esters hydrolyse approximately 20 times faster than simple acetates and phenoxyacetates hydrolyse 50 times faster. Evans and co-workers used ammonia in methanol to remove a methoxyacetate in the presence of two secondary acetate functions and two TES ethers from intermediate 341.1 en route to the marine antitumour agent Altohyrtin C [Scheme 4.341]. - Similarly, they used sodium carbonate in methanol to cleave a secondary methoxyacetate in the presence of two methyl... 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

Alkoxyalkanoate esters have been used as prodrugs to improve the oral bioavailability of antiviral agents such as (+)-cyclaradine (carbocyclic arabino-furanosyl adenine) [41]. (+)-Cyclaradine has been shown to be effective against herpes simplex virus in tissue culture at noncytotoxic concentrations. Two prodrugs of (+)-cyclaradine, namely, (+)-cyclaradine-5 -methoxyacetate (CM) and (+)-cyclaradine-5,-ethoxypropionate (CE) (Fig. 2), may be promising candidates... 

Coimnercially acceptable rates were obtained by using a methoxyacetic acid ester as the acyl donor, which is attributed to hydrogen bond formation with the ether oxygen in the active site of the enzyme [20]. As shown in Scheme 6.6, the process affords an amide of the reacting enantiomer together with the other enan-homer as the free amine. 

CN (1 S-< is)-methoxyacetic acid 2-[2-((3-(l H-ben7.imidazol-2-yl)propyl]methylamino]ethyl)-6-fluoro-l,2,3,4-tetrahydro-1-( 1 -methylethyl)-2-naphthalenyl ester dihydrochloride... 

APRON 2E APRON FL CG 117 CGA 48988 D,L-N-(2,6-DIMETHYLPHENYL)-N-(2 -METHOXYACET-YL)ALANINATE de METHYLE N-(2,6-DIMETHYL-PHENYL)-N-(METHOXYACETYL)-ALANINE METHYL ESTER N-(2,6-DIMETHYLPHENYL)-N-(METHOXY-ACETYL)-DL-AL, NINE METHYL ESTER METALAXIL... 

Methoxyacetates and phenoxyacetates serve as protecting groups in nucleoside synthesis. They are cleaved by aqueous ammonia 20 and 50 times faster respectively than acetic acid esters. In the aromatic series the p-nitrobenzoates often show the advantageous tendency to crystallize. 

Acylases have also been applied to the kinetic resolution of amines. Aminoacylase I from Aspergillus melleus was used for the resolution of a range of arylalkylamines and amino alcohols via acylation with methyl 2 methoxyacetate (Figure 14.13) [19]. Excellent chemoselectivity was also observed in all cases, as the amino group was preferentially acylated in the presence of a primary alcohol functionality. However, poor to moderate enantioselectivity was observed, with values <10. The best result (E = 9.3) was obtained with 1 aminoindane 10 during the conversion to ester 38. 

It has now been reported that the amidation of esters will be used by BASF in the industrial production of amines. A broad range of amines become available in their optically pure form by kinetic resolution using a lipase from Pseudomonas sp. DSM 8246 in the amidation of methoxyacetic acid ethyl ester (see Scheme 12.2-4)[7L... 

The completion of the total synthesis is described in Scheme 69. The Wittig reaction of 479 with LHMDS followed by addition of 466 afforded the desired (Z)-olefin 480 exclusively. Selective removal of methoxyacetate of 480 followed by oxidation and protection afforded TIPS ester 481. Introduction of the diene... 

Interaction of methyl 2-chloro-2-methoxyacetate and a benzene derivative gives the corresponding O-methylmandelic ester in yields of up to 90%, and... 

Glycosylation. The 1-O-methoxyacetoxyl group of sugar derivatives is replaced by a selected alkoxy unit in a catalyzed reaction. Actually, the ester group does not need to be present, as added methoxyacetic acid can be used as cocatalyst for the glycosylation of the sugars with alcohols. 

Transposition ofallylic methoxyacetates. Allylic methoxyacetates undergo re--rangement at room temperature on treatment with Eu(fod). Synfacial transfer of the ester rv up is observed. The rearrangement is efficient and not subject to steric hindrance, -ccause the metal coordinates with the tether atoms. 

Cleavage of methoxyacetates These esters undergo methanolysis in preference to... 

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