Improvement of an acid phosphatase/DHAP-dependent aldolase cascade reaction by using directed evolution.

To enhance the phosphorylating activity of the bacterial nonspecific acid phosphatase from Salmonella enterica ser. typhimurium LT2 towards dihydroxyacetone (DHA), a mutant library was generated from the native enzyme. Three different variants that showed enhanced activity were identified after one round of epPCR.

Complementary chemoenzymatic routes to both enantiomers of febrifugine.

Two complementary strategies for the synthesis of febrifugine are detailed based on previously developed chemoenzymatic approaches to the 3-hydroxypiperidine skeleton. The introduction of the quinazolone-containing side chain in both strategies was based on an N-acyliminium ion-mediated coupling reaction.

N,N-acetals as N-acyliminium ion precursors: synthesis and absolute stereochemistry of epiquinamide.

A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination of the absolute configuration of the natural product. Key steps in the sequence involved chemoenzymatic formation of an enantiomerically pure cyanohydrin, reductive cyclization to the corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor to enable construction of the second ring.

Biocatalytic reductions: from lab curiosity to "first choice".

Enzyme-catalyzed reductions have been studied for decades and have been introduced in more than 10 industrial processes for production of various chiral alcohols, alpha-hydroxy acids and alpha-amino acids. The earlier hurdle of expensive cofactors was taken by the development of highly efficient cofactor regeneration methods. In addition, the accessible number of suitable dehydrogenases and therefore the versatility of this technology is constantly increasing and currently expanding beyond asymmetric production of alcohols and amino acids.

Nitrile hydrolysis activity of Rhodococcus erythropolis NCIMB 11540 whole cells.

The nitrile hydrolyzing properties of the bacterium strain Rhodococcus erythropolis NCIMB 11540 have been investigated. Using whole cells of the microorganism, a wide variety of aromatic and aliphatic cyanide-containing substrates was successfully hydrolyzed to the corresponding amide or acid. In the case of dicyanides, selective monohydrolysis took place, which was further explored in the desymmetrization of malononitriles resulting in the corresponding cyano amides in enantiomeric excesses of up to 98%.

Simple enzymatic in situ generation of dihydroxyacetone phosphate and its use in a cascade reaction for the production of carbohydrates: increased efficiency by phosphate cycling.

A new enzymatic method for the generation of dihydroxyacetone phosphate (DHAP) using the acid phosphatase from Shigella flexneri (PhoN-Sf) and the cheap phosphate donor pyrophosphate (PPi) is described. The utility of this method was demonstrated in an aldolase-catalyzed condensation carried out in one pot in which DHAP was generated and coupled to propionaldehyde to give a yield of 53% of the isolated dephosphorylated end product.

L-selective amidase with extremely broad substrate specificity from Ochrobactrum anthropi NCIMB 40321.

An industrially attractive L-specific amidase was purified to homogeneity from Ochrobactrum anthropi NCIMB 40321 wild-type cells. The purified amidase displayed maximum initial activity between pH 6 and 8.5 and was fully stable for at least 1 h up to 60 degrees C.

Synthetic applications of aliphatic unsaturated alpha-H-alpha-amino acids.

This article provides an overview of the literature concerning synthetic applications of unsaturated aliphatic amino acids in the period May 2000 to December 2004.

Total synthesis of (+)-epiquinamide.

The stereoselective total synthesis of the novel quinolizidine alkaloid (+)-epiquinamide is presented, starting from the amino acid l-allysine ethylene acetal. Key steps in the synthesis involved a highly diastereoselective N-acyliminium ion allylation and a ring-closing metathesis reaction to provide the bicyclic skeleton. [reaction: see text]

Catalytic N-sulfonyliminium ion-mediated cyclizations to alpha-vinyl-substituted isoquinolines and beta-carbolines and applications in metathesis.

[reaction: see text] Catalytic Sn(OTf)2-induced cyclization of linear, aryl-containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines and tetrahydro-1H-beta-carbolines. The usefulness of the vinyl moiety in the resulting products was demonstrated via the synthesis of various key building blocks for alkaloid structures. The alpha-vinyl moiety was utilized in a [2,3] sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis-based synthesis of vincantril, an antianoxia agent, and a synthetic member of the vincamine type natural products.

Diastereoselective synthesis of (2S,5R)-5-hydroxypipecolic acid and 6-substituted derivatives.

[reaction: see text] Herein, we report a diastereoselective synthesis of the natural product (2S,5R)-5-hydroxypipecolic acid and 6-substituted derivatives thereof. The key step in the synthetic sequence is a novel highly diastereoselective epoxidation reaction of an enantiomerically pure cyclic enamide intermediate.

Amidopalladation of alkoxyallenes applied in the synthesis of an enantiopure 1-ethylquinolizidine frog alkaloid.

A palladium-catalyzed amidation of alkoxyallenes has been developed for the construction of linear allylic N,O-acetals under basic conditions involving (cyclic) amides, sulfonamides, carbamates, and amidophosphates. Application of the methodology provided access to the enantiopure 1-ethylquinolizidine structural motif, which is a key synthon in the synthesis of the naturally occurring poisonous frog quinolizidine 233A and derivatives such as the 1-epi-isomer of quinolizidine 207I.

A pincer auxiliary to force difficult lactamisations.

A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pincer auxiliary in the linear precursor sequence. H-betaAla-Phe-OH and H-Phe-betaAla-OH were chosen as representative model peptides.

Dispelling the myths--biocatalysis in industrial synthesis.

Biocatalysis has emerged as an important tool in the industrial synthesis of bulk chemicals, pharmaceutical and agrochemical intermediates, active pharmaceuticals, and food ingredients. However, the number and diversity of the applications are modest, perhaps in part because of perceived or real limitations of biocatalysts, such as limited enzyme availability, substrate scope, and operational stability. Recent scientific breakthroughs in genomics, directed enzyme evolution, and the exploitation of biodiversity should help to overcome these limitations.

A stereodivergent approach to substituted 4-hydroxypiperidines.

A stereodivergent route toward both diastereomeric forms of functionalized 4-hydroxypiperidines has been successfully developed. This route involves biocatalytic generation of the enantiopure starting materials followed by functionalization via N-acyliminium ion-mediated CC-bond formation.

A novel strategy for the synthesis of medium-sized lactams.

[reaction: see text] A novel method for the synthesis of medium-sized lactams based on an auxiliary-mediated combined tethered/templated strategy is presented. Cyclization by a tethered ring-closing metathesis reaction was followed by a templated transannular aminolysis reaction to give seven- to ten-membered lactams in good yields.

Enantioselective Sulfoxidation Catalyzed by Vanadium Haloperoxidases.

Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypohalous acid. We demonstrate that these enzymes also slowly mediate the enantioselective oxidation of organic sulfides (methyl phenyl sulfide, methyl p-tolyl sulfide, and 1-methoxy-4 (methylthio)benzene) to the corresponding sulfoxides (turnover frequency 1 min(-)(1)). The vanadium bromoperoxidase from the brown seaweed Ascophyllum nodosum converts methyl phenyl sulfide to the (R)-enantiomer of the sulfoxide (55% yield and 85% enantiomeric excess (ee)).