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1-Hydroxytryptophans

Reduction of Nb-acetyl-L-tryptophan methyl ester ((S)-38, Scheme 7) with NaBH3CN/AcOH [19] provides Nb-acetyl-2,3-dihydro-L-tryptophan methyl esters (39a and 40a, 1.4 : 1) in 68% yield as a mixture of diastereomers. These diastereomers (39a and 40a) are easily separated with high performance liquid chromatography (HPLC). Their stereochemistries are de-

Scheme 7 Synthesis of (S)-Nb-acetyl-1-hydroxy- and -1-methoxytryptophan methyl esters termined as shown in Scheme 7 comparing each 1H - NMR spectrum with the known set of diastereomers of Nb-ferf-butoxycarbonyl-2,3-dihydro-L-tryptophan methyl esters (39b and 40b), whose absolute stereochemistries were determined by the Vranken group [20].

The tungstate method is successfully applied to both 39a and 40a resulting in the generation of the same product, Nb-acetyl-1-hydroxy-L-tryptophan methyl ester ((S)-41), in 69 and 67% yields, respectively [21]. The application to the mixture of diastereomers (39a and 40a) without separation gives (S)-41 (69%) as reported previously [22]. Subsequent treatment of (S)-41 with excess ethereal CH2N2 yields Nb-acetyl-1-methoxy-L-tryptophan methyl ester ((S)-42, 94%) [22]. Optical purity of (s)-42 is established to be more than 99% ee by its analysis using chiral column chromatography.

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