Ramón Liz

Enantioselective bioreduction of β-keto sulfones with the fungus Curvularia lunata

Abstract β-Keto sulfones bearing bulky groups are reduced with high enantioselectivities to the corresponding optically active β-hydroxy sulfones by the fungus Curvularia lunata CECT 2130; the cells can be re-used without loss of their catalytic activity.

FUNGAL AND BACTERIAL REGIOSELECTIVE HYDROXYLATION OF PYRIMIDINE HETEROCYCLES

Abstract The bacterium Rhodococcus erythropolis is employed to hydroxylate the anxiolytic lesopitron, and this bacterium, together with Agrobacterium sp. and the fungus Beauveria bassiana , are used to extend the field of hydroxylation of heteroaromatic compounds to a series of unexplored pyrimidines. Of all the substrates investigated, only the carbamate 11a is regioselectively hydroxylated by B. bassiana at the C-5 position of the pyrimidine ring; in contrast, the bacteria are able to regioselectively oxidize, when free, the C-2 and/or C-4 positions of the pyrimidine moiety of all the substrates 1a – 12a , up to a maximum of two oxidations.

Enantioselective reduction of β-keto amides by the fungus Mortierella isabellina

Abstract Incubations of the fungus Mortierella isabellina NRRL 1757 with 3-oxo-3-phenylpropanamide, 3-oxobutanamide and with some of their N -alkyl derivatives afford the corresponding ( S )-3-hydroxyamides, usually in high chemical yields and enantiomeric excesses.

Regioselective and Stereospecific Synthesis of Enantiopure 1,3-Oxazolidin-2-ones by Intramolecular Ring Opening of 2-(Boc-aminomethyl)aziridines. Preparation of the Antibiotic Linezolid†

The amide moiety of several enantiopure unactivated 1-aryl- or 1-alkylaziridine-2-carboxamides were reduced and then N-Boc-protected to afford enantiopure 2-(Boc-aminomethyl)aziridines, which were further converted into enantiopure 5-(aminomethyl)-1,3-oxazolidin-2-ones by means of a stereospecific and fully regioselective BF3.Et2O-promoted intramolecular nucleophilic ring opening. One of these oxazolidinones was transformed into the antibiotic linezolid through a CuI-catalyzed N-arylation reaction at its carbamate moiety.

Synthesis of substituted 2-aminopent-4-enals and 2-amino-3-(2-furyl)propanals via[3,3]- and [1,3]-sigmatropic shifts of β-allyloxyenamines

The presence of an amino substituent at the 2-vinyl position in substituted allyl vinyl ethers facilitates low-temperature rearrangements through [3,3]- or [1,3]-sigmatropic shifts, which lead to the aminoaldehydes (3) and (5), respectively.

Catalytic and non-catalytic addition of aromatic amines to terminal acetylenes in the presence of mercury(II) chloride and acetate

The addition of aromatic amines to terminal acetylenes in the presence of catalytic amounts of mercury(II) chloride gives imines, enamines, and 1,2,3,4-tetrahydroquinoline derivatives; mercury(II) acetate shows considerably less catalytic activity and may be used for the non-catalytic preparation of imines, enamines, NN′-disubstituted acetamidines, and NN-disubstituted acetamides.

Enantiopure trans-3-arylaziridine-2-carboxamides: preparation by bacterial hydrolysis and ring-openings toward enantiopure, unnatural D-α-amino acids.

Several racemic trans-3-arylaziridine-2-carboxamides were prepared and then resolved by Rhodococcus rhodochrous IFO 15564-catalyzed hydrolysis. The resulting enantiopure (2R,3S)-3-arylaziridine-2-carboxamides are adequate substrates to undergo fully stereoselective nucleophilic ring-openings at the C-3 ring position to finally yield enantiopure, unnatural d-α-aminocarboxylic acids. Experimental evidence is provided that suggests the fate of the (2S,3R)-3-arylaziridine-2-carboxylic acids concomitantly formed during the resolution processes. In this context, the similar bacterial resolution of racemic 1-arylaziridine-2-carboxamides and -carbonitriles, previously investigated by our research group, has been partially re-examined.

Synthesis and structural study of new highly lipophilic 1,4-dihydropyridines

A new series of 1,4-dihydropyridines (1,4-DHPs) endowed with ester groups bearing long and functionalised alkoxy chains at the C3 and C5 positions of the nitrogen ring have been prepared from the corresponding β-keto esters which were in turn prepared by a lipase catalysed transesterification reaction. The structural study has been carried out by X-ray crystallography and theoretical calculations at the semiempirical (AM1), ab initio (HF/6-31G*) and B3LYP/6-31G* levels and reveals that the long alkyl chains do not have any influence on the required geometry of the 1,4-DHPs for biological activity. However, these chains have a strong impact on the lipophilicity and, therefore, they could be used to gain a better control of the duration of the pharmacological action.

Oxidative alkyl- and aryl-aminomercuriation of prop-2-ynyl alcohols. Synthesis of N-substituted α-iminoketones, α-di-imines, and α-aminopropionamidines

Addition of primary aliphatic or aromatic amines to prop-2-ynol (1a), 1-phenylprop-2-ynol (5a), and oct-1-yn-3-ol (5b) in the presence of mercury(II) acetate leads to the precipitation of metallic mercury and the formation of the corresponding oxidation products. The oxidation of alcohols (5a) and (5b) in the presence of aromatic amines leads to α-aminoketones (6), whereas α-di-imines (7) are obtained from aliphatic amines. The reaction of alcohol (1a) and aliphatic amines yields α-di-imines (2); in contrast, α-di-imines (2) or α-aminoamidines (3) can, alternatively, be synthesized from aromatic amines. A mechanism involving the mercury(II) acetate-promoted addition of an amine to a carbon–carbon triple bond and an allylic oxidation, followed by the successive formation of α-iminoketones, α-di-imines, and α-aminoamidines is proposed.

Hydrazinomercuriation of terminal alkynes and 3-alken-1-ynes. Syntheses of hydrazones and 1-amino-1-aza-1,3-dienes

Although hydrazines cannot be directly added to non-activated, terminal acetylenes in the presence of mercury(II) salts, this difficulty was circumvented by treating hydrazines with 1-alkynylmercury trifluoroacetates (2); in this way, several hydrazones (4a–h) and 1-amino-1-aza-1,3-dienes (4i–m) were easily prepared.