Giuliana Pitacco

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.

A chemoenzymatic approach to the synthesis of enantiomerically pure aza analogues of paraconic acid methyl ester and both enantiomers of methyl β-proline

Abstract Enantiopure methyl esters of 1-alkyl-5-oxo-3-pyrrolidinecarboxylic acids were obtained by enzymatic resolution of the corresponding chiral racemic mixtures. A particularly favourable interaction, also supported by molecular mechanics calculations, was observed between the 1-benzyl derivative and α-chymotrypsin, for which the enantiomeric ratio, E , exceeded 200. The absolute configurations of the lactams were determined by means of CD spectroscopy. From the resulting enantiomerically pure (99% e.e.) ( S )-(+)-1-benzyl-3-pyrrolidinecarboxylic acid and methyl ( R )-(−)-1-benzyl-3-pyrrolidinecarboxylate, the methyl esters of (+) and (−)-β-proline were synthesised in 99% e.e. and 18 and 22% overall yield, respectively.

Vinylamines—XIV : Nitroalkylation of enaminic equilibrium mixtures

Abstract A rapid equilibrium is present in enaminic systems derived from 3-substituted cyclohexanones. Their reactions with β-nitrostyrene have been studied and the stereochemical implications discussed.

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.

Efficient chemoenzymatic synthesis of chiral pincer ligands.

Chiral, nonracemic pincer ligands based on the 6-phenyl-2-aminomethylpyridine and 2-aminomethylbenzo[h]quinoline scaffolds were obtained by a chemoenzymatic approach starting from 2-pyridyl and 2-benzoquinolyl ethanone. In the enantiodifferentiating step, secondary alcohols of opposite absolute configuration were obtained by a bakers yeast reduction of the ketones and by lipase-mediated dynamic kinetic resolution of the racemic alcohols. Their transformation into homochiral 1-methyl-1-heteroarylethanamines occurred without loss of optical purity, giving access to pincer ligands used in enantioselective catalysis.

Bicyclic 1,2-oxazine N-oxides. Different behaviour in ring fission between systems derived from 5- and 6-membered ring cyclic enamines

Abstract 1,2-Oxazine N-oxides derived from aminocyclohexenes open into the corresponding nitroalkylated trisubstituted enamines, whereas those derived from aminocyclopentenes give stable tetrasubstituted enamines. Both open-chain systems are easily hydrolyzed to the corresponding γ-nitrocycloalkanones.

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.

Octaline and decalone derivatives from a new annulation reaction in enamine field

Abstract An octaline system is obtained from the reaction between 2-cyclohexenyl-1-morpholino-ethene and β-nitrostyrene, carried out under kinetic control. By hydrolysis, it is converted to a 1-decalone derivative, which is also a kinetic control product. The stereochemical aspects of formation and equilibration of the products are examined.

Vinylamines—XV : Unusual stereochemical course in nitroalkylation of biased enaminic systems

Reactions between 1-nitropropene and 3-phenyl-, 3-t-butyl- and 4-t-butyl-cyclohexanone enamines are described. Both parallel and antiparallel attacks of the olefin on the substrates are possible.