Vicente Gotor

Hydrolases: catalytically promiscuous enzymes for non-conventional reactions in organic synthesis.

During the last three decades the use of hydrolases for the catalysis of environmentally friendly organic processes under mild reaction conditions has been well documented. Hydrolases have shown themselves to be ideal tools for the acceleration of synthetic transformations because of their high stability, catalytic efficiency, commercial availability and broad substrate specificity in a wide spectrum of biocatalyzed processes. In recent years, novel examples have appeared related to non-conventional reactions catalyzed by hydrolytic enzymes. Amongst these, lipases and acylases have gained much attention as promiscuous biocatalysts showing good levels of reactivity in C-C bond formation, C-heteroatom bond formation, oxidative processes, and novel hydrolytic reactions. This critical review covers recent investigation in the field of catalytic promiscuity, and highlights the most surprising and uncommon activities that this class of enzymes shows in organic synthetic transformations (111 references).

Asymmetric Organic Synthesis with Enzymes

METHODOLOGY Medium Engineering: Directed evolution: The search for new enzymes: SYNTHETIC APPLICATIONS Dynamic Kinetic Resolutions: Deracemization and Enantioconvergent Processes: Transesterification and hydrolysis of carboxylic acid derivatives, alcohols and epoxides Aminolysis and ammonolysis of carboxylic acid derivatives: Reduction Reactions: Oxidation Reactions: Making and breaking C-C bonds:

Non-conventional hydrolase chemistry: amide and carbamate bond formation catalyzed by lipases.

Biocatalysis in nonaqueous media is becoming increasingly important in organic synthesis. Lipases are the most used enzymes, especially in transesterification reactions. However, in the last years the amidation reaction catalyzed by lipases has also been shown to be a useful tool for the organic chemists. In this review, we discuss the possibilities of the enzymatic aminolysis and ammonolysis reactions for the preparation of different amides and for the resolution of esters, amines and aminoalcohols. The enzymatic alkoxycarbonylation of amines opens a new way for the synthesis of chiral carbamates.

Parallel kinetic resolution of racemic mixtures: a new strategy for the preparation of enantiopure compounds?

Kinetic resolution of racemic mixtures is a well-established methodology for the preparation of optically active compounds. However, excellent enantioselectivities are required to obtain them in enantiopure form, due to the decrease in ee when conversion values are close to 50%. To overcome this limitation, a parallel (asymmetric) reaction can remove the disfavored enantiomer. In this review, several examples of this strategy showing its wide range of applicability are described, as well as their mathematical treatment and some new applications in combinatorial chemistry.

Update 1 of: Enantioselective Enzymatic Desymmetrizations in Organic Synthesis

Update 1 of: Enantioselective Enzymatic Desymmetrizations in Organic Synthesis Eduardo García-Urdiales, Ignacio Alfonso, and Vicente Gotor* Departamento de Química Org anica e Inorg anica, Facultad de Química, Universidad de Oviedo, Juli an Clavería, 8, 33006 Oviedo, Spain, and Departamento de Química Biol ogica y Modelizaci on Molecular, Instituto de Química Avanzada de Catalu~na (IQAC, CSIC), Jordi Girona, 18-26, 08034, Barcelona, Spain This is a Chemical Reviews Perennial Review. The root paper of this title was published in Chem. Rev. 2005, 105 (1), 313 354, DOI: 10.1021/cr040640a; Published (Web) December 17, 2004. Updates to this text appear in red type.

Mimicking nature: synthetic nicotinamide cofactors for C═C bioreduction using enoate reductases.

A series of synthetic nicotinamide cofactors were synthesized to replace natural nicotinamide cofactors and promote enoate reductase (ER) catalyzed reactions without compromising the activity or stereoselectivity of the bioreduction process. Conversions and enantioselectivities of >99% were obtained for C═C bioreductions, and the process was successfully upscaled. Furthermore, high chemoselectivity was observed when employing these nicotinamide cofactor mimics (mNADs) with crude extracts in ER-catalyzed reactions.

Lipase catalyzed aminolysis of ethyl propiolate and acrylic esters. Synthesis of chiral acrylamides

Abstract Candida cylindracea lipase is a useful catalyst for the preparation of propiolamides. Candida antarctica lipase efficiently catalyzes the aminolysis of different acrylic esters and aliphatic amines; if racemic amines are used, the corresponding optically active acrylic amide is obtained in moderate-high enentiomeric excess.

Enzymatic aminolysis and transamidation reactions

Abstract Chiral amides obtained from (±)-2-chloropropionate esters and a wide range of amines when the reaction is catalysed by Candida cylidracea lipase. The enantioselection of the enzyme in this aminolysis reaction depends on the substrate and nucleophile structure and reaction conditions. This lipase can catalyze a transamidation reaction if N-trifluoroethyl-2-chloropropionamide is used as substrate. In this way, amides are obtained in high-moderate enantiomeric excesses. The aminolysis of ethyl (±)-2-methylbutyrate with aliphatic amines is achieved using CC and PS lipases as catalysts.

CANDIDA ANTARCTICA LIPASE CATALYZED RESOLUTION OF ETHYL ()-3-AMINOBUTYRATE

Abstract Candida antarctica lipase efficiently catalyzes acetylation and hydrolysis of ethyl (±)-3-aminobutyrate.

Chemoenzymatic Transformationsin Nucleoside Chemistry

Summary. The synthetic potential of enzymes in connection with nucleoside analogue preparations is described.