Enantioselective Organocatalysis-Based Synthesis of 3-Hydroxy Fatty Acids and Fatty γ-Lactones.

3-Hydroxy fatty acids have attracted the interest of researchers, since some of them may interact with free fatty acid receptors more effectively than their non-hydroxylated counterparts and their determination in plasma provides diagnostic information regarding mitochondrial deficiency. We present here the development of a convenient and general methodology for the asymmetric synthesis of 3-hydroxy fatty acids. The enantioselective organocatalytic synthesis of terminal epoxides, starting from long chain aldehydes, is the key-step of our methodology, followed by ring opening with vinylmagnesium bromide.

β-Lactones: A Novel Class of Ca-Independent Phospholipase A (Group VIA iPLA) Inhibitors with the Ability To Inhibit β-Cell Apoptosis.

Ca-independent phospholipase A (GVIA iPLA) has gained increasing interest recently as it has been recognized as a participant in biological processes underlying diabetes development and autoimmune-based neurological disorders. The development of potent GVIA iPLA inhibitors is of great importance because only a few have been reported so far. We present a novel class of GVIA iPLA inhibitors based on the β-lactone ring.

2-Oxoesters: A Novel Class of Potent and Selective Inhibitors of Cytosolic Group IVA Phospholipase A.

Cytosolic phospholipase A (GIVA cPLA) is the only PLA that exhibits a marked preference for hydrolysis of arachidonic acid containing phospholipid substrates releasing free arachidonic acid and lysophospholipids and giving rise to the generation of diverse lipid mediators involved in inflammatory conditions. Thus, the development of potent and selective GIVA cPLA inhibitors is of great importance. We have developed a novel class of such inhibitors based on the 2-oxoester functionality.

Microsomal prostaglandin E synthase-1 inhibitors: a patent review.

Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E (PGE) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents.

Autotaxin inhibitors: a patent review (2012-2016).

Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline. The ATX/LPA axis has received increasing interest in recent years because both the enzyme ATX and the bioactive lipid LPA are involved in various pathological conditions such as tumor progression and metastasis, fibrotic diseases, autoimmune diseases, arthritis, chronic hepatitis, obesity and impaired glucose homeostasis. Thus, a great effort has been devotd in developing synthetic ATX inhibitors as new agents to treat various diseases including cancer and fibrotic diseases.

Visible-Light-Mediated Catalytic Hydroacylation of Dialkyl Azodicarboxylates by Graphite Flakes.

A novel and efficient metal-free catalyzed hydroacylation of dialkyl azodicarboxylates is reported. Graphite flakes were found to be the most efficient catalyst among other carbon-based materials to promote this reaction. This unprecedented catalytic activity can be expanded into a wide substrate scope of aliphatic aldehydes bearing various functional groups, leading to the corresponding products in good to excellent yields.

Inhibitors of phospholipase A and their therapeutic potential: an update on patents (2012-2016).

The regulation of the catalytic activity of the various phospholipase A enzymes is of high importance because these enzymes are involved in various pathological conditions such as arthritis, cardiovascular diseases, neurological diseases, and cancer. Thus, a great effort has been devoted in developing synthetic inhibitors as new agents to treat inflammatory diseases. Some of them have reached clinical trials.

Development of Potent and Selective Inhibitors for Group VIA Calcium-Independent Phospholipase A2 Guided by Molecular Dynamics and Structure-Activity Relationships.

The development of inhibitors for phospholipase A2 (PLA2) is important in elucidating the enzymes implication in various biological pathways. PLA2 enzymes are an important pharmacological target implicated in various inflammatory diseases. Computational chemistry, organic synthesis, and in vitro assays were employed to develop potent and selective inhibitors for group VIA calcium-independent PLA2.

One-pot synthesis of O-allylhydroxylamines through the organocatalytic oxidation of tertiary allylic amines followed by a [2,3]-meisenheimer rearrangement.

A cheap, green, and highly efficient one-pot method for the synthesis of O-protected allylic alcohols is described. By utilizing 2,2,2-trifluoroacetophenone as the organocatalyst and H2 O2 as the oxidant, a variety of allylic amine N-oxides were synthesized, which upon heating are converted to the final products through a [2,3]-Meisenheimer rearrangement.

Photoorganocatalytic hydroacylation of dialkyl azodicarboxylates by utilising activated ketones as photocatalysts.

A fast and efficient visible-light metal-free hydroacylation of dialkyl azodicarboxylates is described. Among a variety of activated ketones, phenyl glyoxylic acid and its ethyl ester were identified as suitable photoorganocatalysts. A range of aliphatic and aromatic aldehydes were employed, thus leading to products in high to excellent yields.

2,2,2-Trifluoroacetophenone: an organocatalyst for an environmentally friendly epoxidation of alkenes.

A cheap, mild, fast, and environmentally friendly oxidation of olefins to the corresponding epoxides is reported using polyfluoroalkyl ketones as efficient organocatalysts. Namely, 2,2,2-trifluoroacetophenone was identified as an improved organocatalyst for the epoxidation of alkenes. Various olefins, mono-, di-, and trisubstituted, are epoxidized chemoselectively in high to quantitative yields utilizing 2-5 mol % catalyst loading and H2O2 as the green oxidant.

2,2,2-Trifluoroacetophenone as an organocatalyst for the oxidation of tertiary amines and azines to N-oxides.

A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding N-oxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2-Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high-to-quantitative yields utilizing 10 mol % of the catalyst and H2 O2 as the oxidant.

Novel pyrrolidine-thiohydantoins/thioxotetrahydropyrimidinones as highly effective catalysts for the asymmetric Michael addition.

The synthesis of novel organocatalysts consisting of a pyrrolidine moiety and a thiohydantoin or a thioxotetrahydropyrimidinone ring is described. The compound combining the pyrrolidine with the thioxotetrahydropyrimidinone was found to be a highly effective catalyst for the Michael reaction. Low catalyst loadings (1-2.