Patrizia Nitti

Acetic acid bacteria as enantioselective biocatalysts

Acetic acid bacteria (five strains of Acetobacter and five strains of Gluconobacter) were used for the biotransformation of different primary alcohols (2-chloropropanol and 2-phenylpropanol) and diols (1,3-butandiol, 1,4-nonandiol and 2,3-butandiol). Most of the tested strains efficiently oxidized the substrates. 2-Chloropropanol and 1,3-butandiol were oxidized with good rates and low enantioselectivity (enantiomeric excess = 18-46% of the S-acid), while microbial oxidation of 2-phenylpropanol furnished (S)-2-phenyl-1-propionic acid with enantiomeric excess (e.e.) >90% with 10 strains. The dehydrogenation of 2,3-butandiol was strongly dependent on the stereochemistry of the substrate; the meso form gave S-acetoin with all the tested strains, the only exception being a Gluconobacter strain. The formation of diacetyl was observed only by using R,R-2,3-butandiol with Acetobacter strains. Oxidation of 1,4-nonandiol gave γ-nonanoic lactone in one step, although with moderate enantioselectivity. 2002 Elsevier Science B.V. All rights reserved.

Microbial bioreductions of γ- and δ-ketoacids and their esters

Abstract A series of yeasts were used in the bioreductions of aliphatic and aromatic γ- and δ-ketoacids and esters to investigate the preparation of enantiomerically pure γ- and δ-lactones through the intermediacy of their corresponding γ- and δ-hydroxyacids and esters. Bioreduction of ethyl 4-oxononanoate 2a with Pichia etchellsii afforded the γ-nonanolide (+)- 5a with 99% e.e., while Pichia minuta proved to be the best choice for the bioreduction of ethyl 2-oxocyclohexylacetate 2e , which afforded cis -(−)- 5e and trans -(−)- 5e with 98 and 99% e.e., respectively. Reduction of 3-(2-oxocyclohexyl)propionic acid 3e with Pichia glucozyma gave predominantly the corresponding δ-lactone trans -(−)- 6e with 94% e.e., whose absolute configuration was determined by means of CD spectroscopy.

Carbo- and heterocyclization reactions of 2-(4-morpholinyl)-1-phenylpropene and nitroolefins

Abstract The title enamine may exist in two double bond isomers. Both forms react with the nitroolefins under different conditions to afford, after hydrolysis, regioisomeric ℘-nitroketones. ℘-Dicarbonyl compounds are isolated from the hydrolysis at pH 2 of the 1,2-oxazine N-oxide systems, which in some cases have also been separated.

Synthesis of all stereoisomers of cognac lactones via microbial reduction and enzymatic resolution strategies

Abstract Both enantiomers of the diastereomeric cognac lactones have been synthesised using enzyme assisted reactions in the enantiodifferentiating step. This was accomplished by bakers yeast reduction of their precursors 3-methyl-4-oxononanoic acid and ester and by enzymatic hydrolysis of the latter. An inhibition of hydrolases by the products was observed. Trans -(+)-, trans -(−)-, cis -(+)- and cis -(−)-cognac lactones having 99, 88, 88 and 99% e.e., respectively, were thus obtained. Their CD spectra have also been studied.

Highly diastereoselective synthesis of cyclic nitronic esters from 1-(4-morpholinyl)-1-phenylpropene with nitroolefins

Abstract 1,2-Oxazine N-oxide derivatives could be obtained as pure isomers from the title reagents. In methanol, they opened into the corresponding Michael-type adducts, as single double bond diastereoisomers. Hydrolyses of both the systems were also highly diastereoselective, leading to ℘-diketones in the former case and to ℘-nitroketones in the latter.

Enantiomerically pure tetrahydro-5-oxo-2-furancarboxylic esters from dialkyl 2-oxoglutarates

Abstract Enantiomerically pure tetrahydro-5-oxo-2-furancarboxylic esters can be prepared either by enzymatic resolution of the racemic γ-lactones themselves or by bioreduction with bakers yeast of dialkyl 2-oxoglutarates and subsequent cyclization of the resulting dialkyl 2-hydroxyglutarates. The best results were obtained by the former route, by which the desired compounds were isolated in high enantiomeric excess. Bioreductions were less satisfactory. In fact the hydroxyester intermediates were initially formed as racemic mixtures and their final enantiomeric enrichment was reached by asymmetric destruction, occurring in the bioreaction medium, however at the same time large amounts of alkyl 4-hydroxybutanoates were formed as side products.

Bicyclic γ-butyrolactones. Relation between conformation of the lactone ring and chiroptical properties

Abstract The CD curves of a set of condensed γ-butyrolactones have been investigated. A simple correlation between the sign of the Cotton effect (CE) and the configuration of C α can be deduced from the resulting data.

A facile route to (+)- and (–)-trans-tetrahydro-5-oxo-2-pentylfuran-3-carboxylic acid, precursors of (+)- and (–)-methylenolactocin

The enantioselective synthesis of the title γ-lactone intermediates is easily achieved by employing Porcine pancreas lipase catalysed hydrolysis of the corresponding esters as the key step.

Synthesis of enantiomerically pure bicyclic condensed δ-lactones via microbial reduction and enzymic resolution strategies

Abstract The formation of enantiopure δ-lactones condensed with alicyclic rings has been achieved either by reduction with bakers yeast of the corresponding δ-keto esters and δ-keto acids or by enzymic resolution of the former compounds. The absolute configurations of the lactones were determined by means of CD spectroscopy, using the correlation method.

Baker's yeast reduction of cyclic δ-ketoesters: synthesis and chiroptical properties of condensed δ-lactones

Abstract Enantiomerically pure condensed δ-lactones have been prepared from the corresponding δ-ketoesters by the use of Saccharomyces cerevisiae . The reactions were not only highly enantioselective but also highly diastereoselective, provided the bakers yeast was preincubated at 50°C for 30 min. Interestingly, and contrary to what is usually found, the use of nutrients inhibited the bioreductions. The relative configurational assignments have been made by means of NMR, while the absolute configurations and conformations of the lactone rings were attributed by means of CD studies.