Sintese de (R)-(-)-ariletanolaminas via redução microbiologica utilizando-se fermento de pão (Saccharomyces cerevisiae) na criação do centro quiral

AUTOR(ES)

Margarete Marques

DATA DE PUBLICAÇÃO

1991

RESUMO

This work describes the synthesis of (R)-(-)-Arylethanolamines which present sympathomimetic properties and form an important class of biologically active compounds. The initial step of this work was the creation of the asymmetric center, by microbiological reduction of derivatives of acetophenone (ArCOCH2X where X= CI or N3) using baker s yeast (Saccharomyces cerevisiae), which was carried out by three differents procedures: Method A - with addition of sucrose. Method B - without addition of sucrose or ethanol. Method C - bioreduction in organic systems (water and solvent). The (-) - b-ethanolamines were prepared by two different synthetic routes. In the first synthetic route ArCOCH2CI ( where Ar= phenyl or substituted phenyl at positions 3 , 4 or 5 , with OH) was first reduced by baker s yeast. In this manner, a-chloroacetophenone (40) was reduced to (R)-(-) -2-chloro-1 -phenylethanol ( 41) with a chemical yield of 74%. This halohydrin underwent epoxidation in basic medium (NaOH) forming (R)-(+)-styrene oxide (17) with a chemical yield of 89%. This epoxide was then reacted with several different amines such as dimethylamine, 2-aminopyridine and aIso ammonia. In this manner, the pharmaceutical products (-)-ubine hydrochloride ((-)-N,N-dimethyl-b-hydroxy-b-phenethylamine hydrochloride) (42), (-) phenyramidol (2-(b-hydroxy phenethylamino)-pyridine) (43) and (-)-phenylethanolamine ((-)-1-phenyl-2-aminoethanol) (5) were obtained. In an attempt to obtain phenolic arylethanolamines from 3 -hydroxyacetophenone (44), the phenolic hydroxyl was first protected by reaction with benzyl chloride to produce 3 -benzyloxyacetophenone (45). The microbiological reduction of 45 gives the alcohol 46. The chlorination of 45 at the a position was carried out with hexachloro-2,4-cyclohexadienone to obtain the compound 50 which was reduced by baker s yeast to produce the chlorohydrin 51. However, this reaction was not reproducible. In the second synthetic route a-azidoacetophenone (62) was reduced by baker s yeast to the corresponding azidoalcohol (19) with a chemical yield of only 24%. The compound 19 was hydrogenated to obtain (R) -(-)-phenylethanolamine (5).

ASSUNTO(S)

processos quimicos

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