Chemoenzymic Synthesis of D-N-Boc-3,5- dihydroxy-4-methoxyphenylglycine

The authors describe an efficient synthesis of nonproteinogenic title amino acid I, an important building block in the synthesis of vancomycin-type antibiotics. The chirality was introduced by AMANO acylase-catalyzed enantioselective hydrolysis, and the overall yield of I was 36% starting from 3,5-bis(isopropoxy)-4-methoxybenzaldehyde. The efficiency of both protease- and acylase-catalyzed hydrolysis reactions depends significantly on the protecting groups used for the two phenoxy functions on the arom. ring. Besides the steric reason, the beneficial effect of the free hydroxy groups in compd. II may be attributed to hydrogen bonding donor properties as well as possible dipole-dipole interactions in the binding region of the enzyme. To the best of the author's knowledge, this the first time that the trifluoroacetyl group has been used as the acyl group in aminoacylase-catalyzed hydrolysis of amides, the main advantages being its easy prepn. and mild chem. hydrolysis. This synthetic route is amenable to the synthesis of I on a multigram scale. [on SciFinder (R)]


Published in:
Journal of Organic Chemistry, 63, 16, 5662-5665
Year:
1998
Keywords:
Note:
CAN 129:230961
34-2
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0022-3263
written in English.
9012-37-7 (Acylase) Role: CAT (Catalyst use), USES (Uses) (AMANO 30000; chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 9001-92-7 (Protease) Role: CAT (Catalyst use), USES (Uses) (Bacillus licheniformis P5459; chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 212758-04-8P Role: BPN (Biosynthetic preparation), BIOL (Biological study), PREP (Preparation) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 212758-02-6P Role: BPN (Biosynthetic preparation), RCT (Reactant), BIOL (Biological study), PREP (Preparation), RACT (Reactant or reagent) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 212758-06-0P; 212758-08-2P Role: BYP (Byproduct), PREP (Preparation) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 1916-07-0 (Methyl 3,4,5-trimethoxybenzoate); 2627-86-3; 171738-30-0 Role: RCT (Reactant), RACT (Reactant or reagent) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 171738-31-1P; 174146-47-5P; 212757-92-1P; 212757-95-4P; 212757-98-7P; 212758-01-5P; 212758-10-6P; 212758-12-8P; 212758-14-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin); 212758-03-7P Role: SPN (Synthetic preparation), PREP (Preparation) (chemoenzymic synthesis of protected [dihydroxy(methoxy)phenyl]glycine as building block for vancomycin)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


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