Functionality at the end of a fatty acid chain – chemical and biological routes to ω‐hydroxylated fatty acids

Hydroxylated fatty acids are valuable compounds in the chemical industry, being used in various products. ω‐Hydroxylated fatty acids are versatile oleochemicals that can be used in polyester and polyamide production. Although a significant number of conventional synthetic chemistry production routes have been developed for ω‐hydroxy acids, considerable challenge relates to their production in price‐competitive, renewable, and sustainable production systems. The development and utilisation of biological systems for ω‐hydroxy acid production may allow the transition of these compounds from specialty chemical to commodity material. The viability of biological routes to ω‐hydroxylated fatty acids is dependent on the identification of enzymes and systems capable of such modifications. Cytochrome P450 monooxygenases are currently the only characterised enzymes known to ω‐hydroxylate fatty acids and yeast provides valuable systems to perform the ω‐hydroxylation biotransformations.     

Antioxidant mechanism of a 3‐arylbenzofuranone containing a 2′‐hydroxyl group

5‐Methyl‐7‐tert‐butyl‐3‐(2′hydroxyl‐5′‐methylphenyl)3H‐benzofuran‐2‐one (PCRBF2), is a better scavenger of 2,2‐diphenyl‐1‐picrylhydrazyl radicals than benzofuranone analogs without the 2′‐substituent, which indicates that PCRBF2 will cause good stabilization in polymers. To prove this further, antioxidation by PCRBF2 and other benzofuranone analogs, namely, 5‐methyl‐7‐tert‐butyl‐3‐(3′,4′‐dimethylphenyl)3H‐benzofuran‐2‐one (OXBF2) and 5‐methyl‐7‐tert‐butyl‐3‐(2′,5′‐dimethylphenyl)3H‐benzofuran‐2‐one (PXBF2), was comparatively studied in polypropylene. The resulting antioxidant activity order of these benzofuranones was PCRBF2 > OXBF2 > PXBF2, an observation showing that the hydroxyl group in the 2′‐position does not weaken the antioxidant activity of benzofuranone, but, on the contrary, increases it. Analyses by FTIR revealed intramolecular hydrogen bonding between the 3‐position hydrogen and the oxygen of the 2′‐hydroxyl group, which makes the 2′‐hydroxyl hydrogen of PCRBF2 more reactive than the 3‐position reactive hydrogen. Thus the hydroxyl group reacts with radicals first. J. VINYL ADDIT. TECHNOL., 19:198‐202, 2013. © 2013 Society of Plastics Engineers     

Photonucleophilic Addition of the ε‐Amino Group of Lysine to a Triflusal Metabolite as a Mechanistic Key to Photoallergy Mediated by the Parent Drug

A mechanism for triflusal‐induced photoallergy involving complexation of 2‐hydroxy‐4‐trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly‐L ‐lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response.

     

Efficient Oxidative Cleavage of Tetrahydrofuran‐2‐methanols to γ‐Lactones by a 2‐Iodobenzamide Catalyst in Combination with Oxone®

An environmentally friendly oxidative cleavage of tetrahydrofuran‐2‐methanols to the corresponding γ‐lactones using a catalytic amount of 2‐iodo‐N‐isopropylbenzamide has been developed. The reaction of various tetrahydrofuran‐2‐methanols with the catalyst in the presence of Oxone^® (2 KHSO₅⋅KHSO₄⋅K₂SO₄) as a co‐oxidant in DMF at room temperature successfully affords the corresponding lactones in good to high yields, and recovery of the catalyst is readily accomplished using a reductive work‐up. This method is notable because it enables the transformation of tetrahydrofuran‐2‐methanols to γ‐lactones under mild conditions without the use of any toxic heavy metals.

     

Solvent extraction — the challenges of a “mature” technology

The solvent extraction area is perceived by some chemical engineers as being mature and fully developed. The present review shows that this is not the case. Many chemical engineering problems must be solved before equipment can be confidently designed from first principles. The review also outlines progress in extraction process chemistry, and in new techniques such as membrane extraction.     

Enantioselective Organocatalytic Rearrangement of α‐Acyloxy‐ β‐keto Sulfides to α‐Acyloxy Thioesters

The first highly enantioselective organocatalytic rearrangement of α‐acyloxy‐β‐keto sulfides to α‐acyloxy thioesters has been developed which provides a number of important synthetic building blocks in high yield and with excellent enantioselectivities (ee: up to 92%).     

Identification of a Δ4‐desaturase from the microalga Ostreococcus lucimarinus

Very long chain PUFA (VLCPUFA) like DHA are essential and health‐beneficial components of the human diet. Due to a shortfall in VLCPUFA supply, research is ongoing to establish VLCPUFA production in heterologous systems like for example oilseed plants. For this purpose it is crucial to identify the required enzymes from primary producers of VLCPUFA. Here, we describe a cDNA from the microalga Ostreococcus lucimarinus coding for a Δ4‐fatty acid desaturase. It exhibits a cytochrome b₅ domain fused to its amino terminus and three histidine boxes that are typically found in front‐end desaturases. Heterologous expression of the partly codon‐optimized version of the cDNA in yeast revealed that the encoded protein catalyzes the desaturation of (n‐3)‐ as well as (n‐6)‐substrates with a preference for VLCPUFA. In yeast it localized at the endoplasmic reticulum (ER) membrane and analysis of the product distribution into different lipid classes suggested that the enzyme most likely acts in a lipid‐dependent manner. Practical applications : The identified Δ4‐desaturase may be useful for the production of DHA in transgenic oleaginous organisms like annual oilseed crops.     

The evolution of US pollution prevention, 1976–2001: a unique chemical engineering contribution to the environment – a review

The importance of pollution prevention or cleaner production has been substantial in changing the environmental approach within advanced industrialized countries. Since the critical factors for pollution prevention success relate to fundamental understanding of diverse industrial processes, chemical engineering has had a major and unique role in this environmental field. Expanding this new and evolutionary topic into the undergraduate curriculum of chemical engineering has also been vital to improving the sustainability of cleaner production. This article describes the fundamental concepts that led to active pollution prevention progress and then the historical progress toward this new paradigm. © 2002 Society of Chemical Industry     

1‐Amino‐1‐hydrazo‐2,2‐dinitroethene – a Hazard Warning

1‐Amino‐1‐hydrazo‐2,2‐dinitroethene ( 2 ) has been observed to spontaneously decompose with considerable violence during storage. Its preparation and handling should be regarded as potentially hazardous.     

Separation of α‐Lactalbumin and β‐Lactoglobulin by a Convenient Liquid‐Solid Extraction System: Application to Milk Whey

A liquid‐solid extraction system based on Tween 80/phosphate was developed. Under the optimized conditions (9 wt % Tween 80, 1.6 : 1 (molar ratio) K₂HPO₄ : NaH₂PO₄, 1.25 mol/L total phosphate, pH = 7.4), α‐Lactalbumin (α‐La) and β‐Lactoglobulin (β‐Lg) were separated with recovery rates of 87.6 % (in the solid polymeric phase) and 98.2 % (in the salt aqueous phase), respectively. Under the effects of water and salt, the solid phase had the ability to form a new liquid‐solid extraction system, and 85.1 % of α‐La could be reversely extracted into the new salt aqueous phase. Following dialysis against water, proteins obtained through extraction and reverse extraction, were analyzed by polyacrylamide gel electrophoresis (PAGE) and thin‐layer scanning. The method was applied successfully to separate α‐La and β‐Lg from milk whey.     

Copper‐Catalyzed Addition of Alkylboranes to Iminoacetates: Access to α‐Alkyl Branched α‐Amino Acids

A copper(I)‐catalyzed addition of alkylborane reagents to α‐iminoacetates has been developed to assemble both acyclic and cyclic α‐branched α‐amino carboxylic acid derivatives in good yields. A wide variety of unactivated alkenes are well tolerated in this transformation.

     

Enantioselective Synthesis of α‐Amino‐γ‐sulfonyl Phosphonates with a Tetrasubstituted Chiral α‐Carbon via Quinine‐Squaramide‐Catalyzed Michael Addition of Nitrophosphonates to Vinyl Sulfones

α‐Nitro‐γ‐sulfonyl phosphonates with a key tetrasubstituted chiral α‐carbon center have been synthesized for the first time in high yield and enantioselectivity through a quinine‐squaramide‐catalyzed conjugate addition of α‐nitro phosphonates to aryl vinyl sulfones. Representative examples presented here for the transformation of nitrosulfonyl phosphonates to aminosulfonyl phosphonates, alkylation at the α‐position of the sulfonyl group followed by desulfonation and scale‐up of the conjugate addition highlight the practical applications of the methodology.     

On the Crystal Structure of the β′-Form of Triglycerides and Structural Changes at the Phase Transitions LIQ. → α → β′ ← β

Based on X-ray single crystal data of the β′-form of triundecanoin the general features of the molecular arrangement in this crystal form have been derived. The unit cell contains eight molecules arranged according to space group P2_1/c, with alternation of the tilt of the hydrocarbon chains in adjacent bimolecular layers. The structure within the molecular layer is quite similar to that of the β-form; the main difference being the chain packing. A second β″-form, β′₂, of triundecanoin has been observed and it differs from the one mentioned above in the orientation of the chain packing subcell 0° in relation to the true unit cell. The polymorphic transitions have been followed by recording of the diffraction pattern versus temperatures. The polymorphic transitions α · β′ · β can be regarded mainly as different lateral arrangement of a dimeric unit. In the α-form the chains are disordered near the methyl end groups, and due to this disorder the structure is closely related to the lamellar liquid-crystalline phase. It is also possible to classify β′-forms according to short-spacing data into a β′₁-type and a β′₂-type, and these groups can be identified also in complex triglycerides.     

How to sleep at night……a guide to internal quality auditing

A quality system cannot really work unless it includes an effective means of internal quality auditing. It cannot be stressed enough that until you routinely check and improve your quality system, you haven't really started. Having decided to implement an internal quality audit system you need to do the job well; after all, the word ‘quality’ is included!     

Titanium‐Mediated Direct Carbon‐Carbon Double Bond Formation to α‐Trifluoromethyl Acids: A New Contribution to the Knoevenagel Reaction and a High‐Yielding and Stereoselective Synthesis of α‐Trifluoromethylacrylic Acids

An efficient strategy for a high‐yielding and stereoselective synthesis of α‐trifluoromethyl unsaturated carboxylic acids directly from the reactions of 3,3,3‐trifluoropropanoic acid (CF₃CH₂COOH) with various aryl aldehydes in the presence of titanium tetrachloride (TiCl₄) is reported here for the first time, which is a valuable expansion for the classical Knoevenagel reaction. Because these compounds may have potential applications in organic electronics and can be easily converted to the corresponding fluorinated alcohols and amino acids with excellent bioactivity, this route should be a good choice for the preparation of α‐trifluoromethyl‐containing derivatives.     

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

Golgi α‐mannosidase II (GMII) is a key enzyme in the N‐glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5α‐substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X‐ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head‐group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well‐organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N‐acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors.     

Evaluation of Palladacycles as a Non‐Rhodium Based Alternative for the Asymmetric Conjugate 1,4‐Addition of Arylboronic Acids to α,β‐Unsaturated Enones

The asymmetric conjugate 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds is an extremely versatile and widely used organic transformation. While the rhodium(I)‐catalysed reaction has been thoroughly explored, the asymmetric palladium‐catalysed protocol is far less developed and understood, particularly with acyclic enones as substrates. Herein, we report the systematic evaluation of a series of metallacycles for this reaction and the conjugate addition of arylboronic acids to a wide range of α,β‐unsaturated enones, catalysed by an easily accessible and robust chiral phosphapalladacycle in high yields and enantioselectivities.

     

Enantioselective Addition of Diphenylphosphine to 3‐Methyl‐4‐nitro‐5‐alkenylisoxazoles

An enantioselective Michael addition reaction of diphenylphosphine to substituted alkenylisoxazoles has been developed. The reaction proceeds efficiently under mild conditions with high yields (up to 99%) and moderate to excellent enantioselectivities (up to 92%) thus providing a hitherto unavailable direct access to a library of chiral tertiary phosphine‐functionalized isoxazoles.