Phenyl isoserines

The reaction of silyl ketene acetal addition to nitrones has been used for the synthesis of optically active (2S,3S)-benzoyl- and /V- oc-phenyl isoserine (636a) of isoxazolidine nucleoside-analog of thymine polyoxine C(636b) and of... 

R,3S)-p-Phenyl-isoserine methyl ester (4.35 g, 22 mM) is dissolved in dry THF (100 ml) and the flask cooled to 0°C. To the mixture is added t-butyl isocyanate (2.8 ml, 25 mM). TLC after 15 min shows some starting material left so additional isocyanate (0.5 ml) is added. TLC after 1 h shows no starting material so the solvent is concentrated under reduced pressure to give the N-(t-butylaminocarbonyl)-p-phenyl isoserine methyl ester. 

The use of lipase-catalyzed ester hydrolyses or transesterification reactions has led, interestingly, to an efficient method for synthesizing the N-benzoyl-(21 ,3S)-3-phenyl isoserine moiety, the C-13 side chain of taxol. The Mucor miehei lipase proved to be uniquely suited for the stereospecific transesterification of racemic methyl fra s-/l-phenyl glycidate. Further improvement of this reaction led to the choice of an isobutanol-hexane mixture (1 1 vol/vol) as the... 

Sharpless catalytic asymmetric aminohydroxylation (AA) provides a direct and efficient route to the taxol side chain as well as a number of other natural products and synthetic ligands. The required asymmetry of the taxol side chain was controlled by (DHQ)2-PHAL, and hydroxyla-tion was achieved with potassium osmate (K20s02(0H)4). Various N-haloamide salts were investigated, and yields and percentage ee were good to excellent under different conditions. For example, reaction of methyl cinnamate under Sharpless catalytic AA conditions gave (2R,3S) N-tosyl-3-phenyl isoserine 7.3.1 in 82% ee in 69% yield. Compound 7.3.1 was then converted to the taxol side chain acid in two steps in good yield (262). 

Recently, Ueno et al used the chiral zirconium catalyst 7.4.4 for asymmetric induction. Thus, reaction of imine 7.4.5 and silyl enol ether 7.4.6 in the presence of 10 mol% S-IAA gave the desired phenyl isoserine derivative 7.4.7 in 94% ee and 95% yield. The a-hydroxy-phenylamine which was required for the catalytic asymmetric induction was then cleaved oxidatively using CAN after being converted to an a-methoxy-phenylamine derivative. Aqueous hydrolysis of the resulting aminoester 7.4.8 yielded the amino acid quantitatively, which was benzoylated to give the taxol side chain (269). 

Hydroxy - 2 - amino - 2-phenylpropionic Acid (2-Am ino- 2-plienyI-lactic acid, 2-phenyl-isoserine)... 

Patel, R.N., Banerjee, A., Howell, J.M., Mcnamee, C.G., Brozozowski, D., Mirfakhrae, D., Nanduri, V., Thottathil, J. K., and Szarka, LJ. (1993) Microbial synthesis of (2R,3S)-(—)-N-benzoyl-3-phenyl isoserine ethyl ester - a taxol side-chain synfhon. Tetrahedron Asymmetry, 4, 2069-2084. 

Patel RN, Banerjee A, Hawell JM, MCNarnee C, Brozozowski D, Mirfakhrae D, Nanduri V, Thottathil JK, Szarka LJ. Microbial synthesis of (2/ ,35)-(—)-iV-benzoyl-3-phenyl isoserine ethyl ester-a taxol side-chain synthon. Tetrahedron Asymm. 1993 4 2069-2084. 

O-Methyl-tyroain-methyleeter 14 II 380. N-Methyl-tyioam.methylestar 14 I 666. O.N-Dimetnyl-tyroain 14 I 669. (f.Phenyl-senn-dthyleater 14II387. jS-Fhenyl-isoserin-athyleater 14 n 389. 

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