Monitoring Changes to Alkenone Biosynthesis in Commercial Tisochrysis lutea Microalgae.

Alkenones are unique lipids produced by certain species of microalgae, well-known for use in paleoclimatology, and more recently pursued to advance sustainability across multiple industries. Beginning in 2018, the biosynthesis of alkenones by commercially grown Tisochrysis lutea (T-Iso) microalgae from one of the world's most established producers, Necton S.A., changed dramatically from structures containing 37 and 38 carbons, to unusual shorter-chain C35 and C36 diunsaturated alkenones (C35:2 and C36:2 alkenones). While the exact reasons for this change remain unknown, analysis of alkenones isolated from T-Iso grown in 2021 and 2023 revealed that this change has persisted. The structure of these rare shorter-chain alkenones, including double bond position, produced by Necton T-Iso remained the same over the last five years, which was determined using a new and optimized cross-metathesis derivatization approach with analysis by comprehensive two-dimensional gas chromatography and NMR. However, noticeable differences in the alkenone profiles among the different batches were observed. Combined with fatty acid compositional analysis, the data suggest a connection between these lipid classes (e.g., increased DHA corresponds to lower amounts of shorter-chain alkenones) and the ability to manipulate their biosynthesis in T-Iso with changes to cultivation conditions.

Regioselective Fluorohydrin Synthesis from Allylsilanes and Evidence for a Silicon-Fluorine Gauche Effect.

Allylsilanes can be regioselectively transformed into the corresponding 3-silylfluorohydrin in good yield using a sequence of epoxidation followed by treatment with HF·Et3N with or without isolation of the intermediate epoxide. Various silicon-substitutions are tolerated, resulting in a range of 2-fluoro-3-silylpropan-1-ol products from this method. Whereas other fluorohydrin syntheses by epoxide opening using HF·Et3N generally require more forcing conditions (e.g., higher reaction temperature), opening of allylsilane-derived epoxides with this reagent occurs at room temperature. We attribute this rate acceleration along with the observed regioselectivity to a ß-silyl effect that stabilizes a proposed cationic intermediate. The use of enantioenriched epoxides indicates that both SN1- and SN2-type mechanisms may be operable depending on substitution at silicon. Conformational analysis by NMR and theory along with a crystal structure obtained by X-ray diffraction points to a preference for silicon and fluorine to be proximal to one another in the products, perhaps favored due to electrostatic interactions.

Hydroxyl-Directed Regio- and Diastereoselective Allylic Sulfone Reductions with [Sm(H2O)n]I2.

Allylic 1,2- and 1,3-hydroxy phenyl sulfones undergo regioselective and diastereoselective desulfonylation with double bond migration upon treatment with [Sm(H2O)n]I2. Selectivity in these reactions is thought to arise from the formation of a chelated organosamarium intermediate followed by intramolecular protonation by samarium-bound water, which is supported by observed diastereoselectivity and stereospecificity trends along with deuterium labeling experiments. The reaction was then featured in the synthesis of the phenolic fragment of the thailandamide natural products.

Sequential iodine-mediated diallylsilane rearrangement/asymmetric dihydroxylation: Synthesis and reactions of enantioenriched oxasilacycles.

Products from an iodine-mediated diallylsilane rearrangement were taken into an asymmetric dihydroxylation (AD) reaction resulting in the formation of diastereomeric 6-membered oxasilacycles. Removal of the epimeric stereocenter among this mixture of diastereomers by elimination of iodine produced a single enantioenriched cyclic allyl silyl ether. The resulting allyl silane was then successfully engaged in several further transformations, providing an alternative means to prepare useful intermediates for enantioselective synthesis.

Production of Two Highly Abundant 2-Methyl-Branched Fatty Acids by Blooms of the Globally Significant Marine Cyanobacteria Trichodesmium erythraeum.

The bloom-forming cyanobacteria Trichodesmium contribute up to 30% to the total fixed nitrogen in the global oceans and thereby drive substantial productivity. On an expedition in the Gulf of Mexico, we observed and sampled surface slicks, some of which included dense blooms of Trichodesmium erythraeum. These bloom samples contained abundant and atypical free fatty acids, identified here as 2-methyldecanoic acid and 2-methyldodecanoic acid. The high abundance and unusual branching pattern of these compounds suggest that they may play a specific role in this globally important organism.

ß-Silyloxy Allylboronate Esters through an Aldehyde Borylation/Homologation Sequence.

The areas of carbonyl borylation and the homologation of carbon-boron bonds have provided a number of fruitful methods in organic synthesis. Combining these approaches, the homologation of α-oxyboronate esters, provides pathways to access complex organoboronate esters stereoselectively. To this end, the homologation of α-silyloxyboronate esters with lithiated allyl chlorides to form ß-silyloxy allylboronate esters is reported. Direct oxidation of the homologation products provides ß-silyloxy allyl alcohols in good yield. The homologation provides a range of allylic alcohols, albeit with low diastereoselectivity.

Evaluation of alkenones, a renewably sourced, plant-derived wax as a structuring agent for lipsticks.

OBJECTIVE: Waxes are used as structuring agents in lipsticks. There are a variety of waxes combined in a single lipstick to provide good stability, pleasant texture and good pay-off. Due to a significant growth for natural, green and sustainable products, there is a constant search for alternatives to animal-derived and petroleum-derived ingredients. In this study, a green, non-animalderived wax, namely long-chain ketones (referred to as alkenones), sourced from marine microalgae was formulated into lipsticks and evaluated as a structuring agent. METHODS: Alkenones were used as a substitute for microcrystalline wax, ozokerite and candelilla wax, typical structuring agents. In total, 384 lipsticks were formulated: L1 (control, no alkenones), L2 (alkenones as a substitute for ozokerite), L3 (alkenones as a substitute for microcrystalline wax) and L4 (alkenones as a substitute for candelilla wax). Products were tested for hardness (bending force), stiffness, firmness (needle penetration), pay-off (using a texture analyser and a consumer panel), friction, melting point and stability for 12 weeks at 25 and 45°C. RESULTS: Alkenones influenced each characteristic evaluated. In general, lipsticks with alkenones (L2-L4) became softer and easier to bend compared to the control (L1). In terms of firmness, lipsticks were similar to the control, except for L4, which was significantly (P < 0.05) firmer. The effect on pay-off was not consistent. L2 and L3 had higher pay-off to skin and fabric than L1. In addition, L4 had the lowest amount transferred, but it still had the highest colour intensity on skin. Alkenones influenced friction (glide) positively; the average friction decreased for L2-L4. The lowest friction (i.e. best glide) was shown in L4. Melting point of the lipsticks was lower when alkenones were present. Overall, L4, containing 7% of 4 alkenones in combination with microcrystalline wax, ozokerite and carnauba wax, was found to have the most desirable attributes, including ease of bending, high level of firmness, low pay-off in terms of amount, high colour intensity on skin and low friction (i.e. better glide). Consumers preferred L4 the most overall. CONCLUSION: Results of this study indicate that alkenones offer a sustainable, non-animal and non-petroleum-derived choice as a structuring agent for lipsticks.

OBJECTIF: Les cires sont utilisées comme agents de structuration dans les rouges à lèvres. Un rouge à lèvres contient plusieurs cires, afin d'obtenir une bonne stabilité, une texture agréable et un bon transfert de matière. En raison d'une croissance significative de la demande en produits naturels, écologiques et durables, les chercheurs s'efforcent constamment de trouver des alternatives aux ingrédients d'origine animale et dérivés du pétrole. Dans cette étude, les cétones à longue chaîne (appelés alkénones), une cire verte qui n'est pas d'origine animale, mais provenant de microalgues marines, a été formulée pour les rouges à lèvres et évaluée comme agent de structuration. MÉTHODES: Les alkénones ont été utilisés comme substitut pour la cire microcristalline, l'ozokérite et la cire de candelilla, des agents de structuration courants. Au total, 384 rouges à lèvres ont été formulés : L1 (contrôle, sans alkénone), L2 (alkénones comme substitut de l'ozokérite), L3 (alkénones comme substitut de la cire microcristalline) et L4 (alkénones comme substitut de la cire de candelilla). Des tests ont été réalisés sur les produits pour évaluer la dureté (force de flexion), la rigidité, la fermeté (pénétration de l'aiguille), le transfert de matière (à l'aide d'un analyseur de texture et d'un panel de consommateurs), la friction, le point de fusion et la stabilité pendant 12 semaines à 25 et 45 °C. RÉSULTATS: Les alkénones ont eu une influence sur chacune des caractéristiques évaluées. En général, les rouges à lèvres contenant des alkénones (L2 à L4) sont devenus plus mous et ont présenté une flexion plus facile que dans le cas du contrôle (L1). En termes de fermeté, les rouges à lèvres étaient similaires au contrôle, à l'exception de L4, qui était significativement (P < 0,05) plus ferme. L'effet sur le transfert de matière a été variable. L2 et L3 ont présenté un transfert de matière sur la peau et le tissu supérieur à celui de L1. En outre, dans le cas de L4, la quantité transférée était la plus faible, mais l'intensité de la couleur sur la peau était toujours la plus élevée. Les alkénones ont eu un effet positif sur la friction (glissement) ; la friction moyenne a diminué pour L2 à L4. La friction la plus basse (c.-à-d. le meilleur glissement) a été observée dans le cas de L4. Le point de fusion des rouges à lèvres était plus bas lorsque des alkénones étaient présents. Dans l'ensemble, L4, contenant 7 % d'alkénones en combinaison avec de la cire microcristalline, de l'ozokérite et de la cire de carnauba, s'est révélée avoir les caractéristiques les plus souhaitables, notamment une facilité de flexion, une fermeté élevée, un faible transfert de matière en termes de quantité, une intensité de couleur élevée sur la peau et une faible friction (c.-à-d. un meilleur glissement). En général, les consommateurs ont préféré L4. CONCLUSION: Les résultats de cette étude indiquent que les alkénones offrent un choix durable, non issu de l'animal et non dérivé du pétrole comme agent de structuration pour les rouges à lèvres.

Chemoselective Carbonyl Allylations with Alkoxyallylsiletanes.

Alkoxyallylsiletanes are capable of highly chemo- and diastereoselective carbonyl allylsilylations. Reactive substrates include salicylaldehydes and glyoxylic acids. Chemoselectivity in these reactions is thought to arise from a mechanism involving first exchange of the alkyoxy group on silicon with a substrate hydroxyl followed by activation of a nearby carbonyl by the Lewis acidic siletane and intramolecular allylation. In this way, substrates containing multiple reactive carbonyl groups (e.g., dialdehyde or triketone) can be selectively monoallylated, even overcoming inherent electrophilicity bias.

Suzuki coupling-based synthesis of VATPase inhibitor archazolid natural product derived fragments.

An archazolid natural product fragment that displays dose-dependent inhibition of the vacuolar-type ATPase (VATPase) has been synthesized by a high-yielding Suzuki coupling of two complex subunits. Similarly, a further simplified fragment was prepared and evaluated for VATPase inhibitory activity. This compound did inhibit the VATPase, as evidenced by growth inhibition of etiolated Arabidopsis seedlings, however at approximately 10× lower potency than the more complex fragment. Cyclooxygenase (COX) enzyme inhibition was not observed for either fragment.

Correction: Suzuki coupling-based synthesis of VATPase inhibitor archazolid natural product derived fragments.

[This corrects the article DOI: 10.1039/C9RA07050H.].

How Persistent and Bioavailable Are Oxygenated Deepwater Horizon Oil Transformation Products?

About half of the surface oil floating on the Gulf of Mexico in the aftermath of the 2010 Deepwater Horizon spill was transformed into oxygenated hydrocarbons (OxHC) within days to weeks. These OxHC persist for years in oil/sand aggregates in nearshore and beach environments, and there is concern that these aggregates might represent a long-term source of toxic compounds. However, because this OxHC fraction is a continuum of transformation products that are not well chemically characterized, it is not included in current oil spill fate and effect models. This challenges an accurate environmental risk assessment of weathered oil. Here, we used molecular and bulk analytical techniques to constrain the chemical composition and environmental fate of weathered oil samples collected on the sea surface and beaches of the Gulf of Mexico. We found that approximately 50% of the weathering-related disappearance of saturated and aromatic compounds in these samples was compensated by an increase in OxHC. Furthermore, we identified and quantified a suite of oxygenated aliphatic compounds that are more water-soluble and less hydrophobic than its presumed precursors, but only represent <1% of the oil residues' mass. Lastly, dissolution experiments showed that compounds in the OxHC fraction can leach into the water; however, the mass loss of this process is small. Overall, this study shows that the OxHC fraction is prevalent and persistent in weathered oil/sand aggregates, which can act as a long-term source of dissolved oil-derived compounds.

Iodine-mediated rearrangements of diallylsilanes.

Diallylsilanes can be made to rearrange upon treatment with I2. Of the silanes tested, diallyldiphenylsilane showed the greatest propensity to undergo this intramolecular carbocation allylation process. After etherification of the initially formed iodosilane, the products from this transformation represent useful synthetic intermediates, suitable for alkylation and cross-metathesis/annulation reactions.

Synthesis of a C1-C23 fragment of the archazolids and evidence for V-ATPase but not COX inhibitory activity.

A convergent synthesis of a C1-C23 fragment of the archazolids has been completed based on a high yielding Stille coupling to costruct the substituted Z,Z,E-conjugated triene. After removal of the protecting groups, the resulting tetrol exhibited evidence for inhibition of the vacuolar-type ATPase (V-ATPase) but not cyclooxygenase (COX) inhibitory activity.

Experimental Protocol for Biodiesel Production with Isolation of Alkenones as Coproducts from Commercial Isochrysis Algal Biomass.

The need to replace petroleum fuels with alternatives from renewable and more environmentally sustainable sources is of growing importance. Biomass-derived biofuels have gained considerable attention in this regard, however first generation biofuels from edible crops like corn ethanol or soybean biodiesel have generally fallen out of favor. There is thus great interest in the development of methods for the production of liquid fuels from domestic and superior non-edible sources. Here we describe a detailed procedure for the production of a purified biodiesel from the marine microalgae Isochrysis. Additionally, a unique suite of lipids known as polyunsaturated long-chain alkenones are isolated in parallel as potentially valuable coproducts to offset the cost of biodiesel production. Multi-kilogram quantities of Isochrysis are purchased from two commercial sources, one as a wet paste (80% water) that is first dried prior to processing, and the other a dry milled powder (95% dry). Lipids are extracted with hexanes in a Soxhlet apparatus to produce an algal oil ("hexane algal oil") containing both traditional fats (i.e., triglycerides, 46-60% w/w) and alkenones (16-25% w/w). Saponification of the triglycerides in the algal oil allows for separation of the resulting free fatty acids (FFAs) from alkenone-containing neutral lipids. FFAs are then converted to biodiesel (i.e., fatty acid methyl esters, FAMEs) by acid-catalyzed esterification while alkenones are isolated and purified from the neutral lipids by crystallization. We demonstrate that biodiesel from both commercial Isochrysis biomasses have similar but not identical FAME profiles, characterized by elevated polyunsaturated fatty acid contents (approximately 40% w/w). Yields of biodiesel were consistently higher when starting from the Isochrysis wet paste (12% w/w vs. 7% w/w), which can be traced to lower amounts of hexane algal oil obtained from the powdered Isochrysis product.

A One-Pot/Single-Analysis Approach to Substrate Scope Investigations Using Comprehensive Two-Dimensional Gas Chromatography (GC×GC).

A representative substrate scope investigation for an enantioselective catalytic ketone-reduction has been performed as a single reaction on a mixture containing equimolar amounts of nine (9) prototypical compounds. The resulting analyte pool containing 18 potential products from nine different reactions could all be completely resolved in a single chromatographic injection using comprehensive two-dimensional gas chromatography (GC×GC) with time-of-flight mass spectrometry, allowing for simultaneous determination of percent conversion and enantiomeric excess for each substrate. The results obtained for an enantioselective iron-catalyzed asymmetric transfer hydrogenation using this one-pot/single-analysis approach were similar to those reported for the individualized reactions, demonstrating the utility of this strategy for streamlining substrate scope investigations. Moreover, for this particular catalyst, activity and selectivity were not greatly affected by the presence of other ketones or enantioenriched reduced products. This approach allows for faster and greener analyses that are central to new reaction development, as well as an opportunity to gain further insights into other established transformations.

Synthesis of the C1-C17 fragment of the archazolids by complex cis-homodimer cross metathesis.

A synthesis of the C1-C17 fragment of the archazolids is described featuring a complex cross-metathesis coupling reaction between a cis-homodimer (prepared by silyl-tethered ring-closing metathesis) and the Z,Z-terminal triene containing "eastern domain" of the archazolid natural products. This cross-metathesis was only successful when using the cis- as opposed to the monomer or trans-homodimer, with the cis-dimer added batchwise to minimize cis/trans-isomerization. The product was obtained in an optimized 78% yield using the Hoveyda-Grubbs catalyst at 50 °C in toluene.

Exploring a Ring-Closing Metathesis Approach to the Archazolid Macrocycle.

The synthesis of a new "eastern domain" of a proposed dihydroarchazolid analogue is described along with initial results from attempted macrocyclization by RCM. This work has revealed a competing backbiting process that may be preventable by alcohol functionalization and installation of a metathesis relay.

Stereocontrolled synthesis of 1,3-diols from enones: cooperative Lewis base-mediated intramolecular carbonyl hydrosilylations.

A streamlined synthesis of ß-hydroxy ketone substrates has been developed to further investigate a recently discovered cooperative Lewis base-mediated intramolecular carbonyl hydrosilylation reaction. The synthesis features an enone ß-borylation/oxidation sequence that has proven to be quite general and high-yielding. This has allowed for additional investigations into the diastereoselectivity of the hydrosilylation reaction through the preparation of important polyketide fragments.

Synthesis and activity of the archazolid western hemisphere.

A convergent and scalable synthesis of the archazolid western hemisphere has been completed. The V-ATPase inhibitory activity of this compound along with a previously prepared eastern domain was then tested using a convenient Arabidopsis-based V-ATPase assay.

Chemoselective samarium-mediated benzoyloxysulfone eliminations.

An investigation of the substrate dependence on the rate of samarium-mediated reductive elimination of ß-acyloxysulfones has provided insights into the mechanism of this transformation and allowed for the development of a chemoselective elimination process.