New stereospecific synthesis of Tesaglitazar and Navaglitazar precursors

A new synthetic route of to pharmaceutical intermediates (S)-1a–b and (S)-14 is reported. The reaction pathway is based on the baker’s yeast-mediated reduction of the α-alkoxy cinnamaldehydes 9a–c to give the corresponding (S)-alcohols in good yields and excellent ee.

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(S)-2-Ethoxy-3-(4-methoxyphenyl)propan-1-olC12H18O3Ee = 99%[α]D20=+4.0 (c 3.52, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (S)

(S)-2-Methoxy-3-(4-methoxyphenyl)propan-1-olC11H16O3Ee = 95%[α]D20=-3.4 (c 1.16, EtOH)Source of chirality: baker’s yeast reductionAbsolute configuration: (S)

(S)-2-Allyloxy-3-(4-methoxyphenyl)propan-1-olC13H18O3Ee = 99.9%[α]D20=-2.9 (c 1.16, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (S)