Synthesis Of Fragrances Research Articles

Nature stays natural: two novel chemo-enzymatic one-pot cascades for the synthesis of fragrance and flavor aldehydes.

Novel synthetic strategies for the production of high-value chemicals based on the 12 principles of green chemistry are highly desired. Herein, we present a proof of concept for two novel chemo-enzymatic one-pot cascades allowing for the production of valuable fragrance and flavor aldehydes. We utilized renewable phenylpropenes, such as eugenol from cloves or estragole from estragon, as starting materials. For the first strategy, Pd-catalyzed isomerization of the allylic double bond and subsequent enzyme-mediated (aromatic dioxygenase, ADO) alkene cleavage were performed to obtain the desired aldehydes. In the second route, the double bond was oxidized to the corresponding ketone via a copper-free Wacker oxidation protocol followed by enzymatic Baeyer-Villiger oxidation (phenylacetone monooxygenase from Thermobifida fusca), esterase-mediated (esterase from Pseudomonas fluorescens, PfeI) hydrolysis and subsequent oxidation of the primary alcohol (alcohol dehydrogenase from Pseudomonas putida, AlkJ) to the respective aldehyde products. Eight different phenylpropene derivatives were subjected to these reaction sequences, allowing for the synthesis of seven aldehydes in up to 55% yield after 4 reaction steps (86% for each step).

Preparation, characterization and properties of linalool and acyclic cucurbit[n]urils inclusion complexes

AbstractLinalool is an important substance in the synthesis of fragrances owing to its unique aroma. However, the application of linalool is limited due to its low stability and rapid volatilization. Supramolecular inclusion technology plays an important role in improving the stability and volatility of fragrance and endows fragrance with excellent heat‐controlled release properties. In this study, inclusion complexes were prepared with two acyclic cucurbit[n]urils (M1 and M2) to improve the thermal stability of linalool, their binding behaviours were investigated by NMR, XRD, FT‐IR and Molecular Docking, confirming the formation of the host‐guest inclusion complexes. The stoichiometry of inclusion complexes was 1:1 by Job's plot and the binding constant was determined by fluorescence titration. The TG and heat‐controlled release experiment indicated that the inclusion complexes have higher thermal stability. This study provides a new idea and method for the development of linalool series spices.

Low-Temperature Infrared Spectra and Ultraviolet-Induced Rotamerization of 5-Chlorosalicylaldehyde.

5-Chlorosalicylaldehyde (abbreviated as 5CSA) is an important chemical used in the synthesis of fragrances, dyes, and pharmaceuticals. In this investigation, 5CSA isolated in solid N2, at 10 K, and in its neat amorphous and crystalline phases, at 50 and 190 K, respectively, were investigated by infrared spectroscopy and DFT(B3LYP)/6-311++G(d,p) calculations. The systematic theoretical analysis of the 5CSA conformational landscape showed that the compound exhibits four different conformers, which were structurally characterized in detail. In the as-deposited low-temperature matrices of 5CSA, only the most stable conformer, the intramolecularly hydrogen-bonded form I, was found. The same was observed in the case of the investigated low-temperature amorphous and crystalline phases of 5CSA. Conformer I was successfully converted into a higher-energy conformer(II), where both aldehyde and hydroxyl groups are rotated by 180° relative to their position in the initial conformer, through narrowband ultraviolet (UV) (λ = 308 nm) in situ irradiation of the as-deposited N2 matrix of 5CSA. The infrared spectra of both matrix-isolated conformers, as well as those of the neat amorphous and crystalline phases of 5CSA, were assigned and interpreted in comparative terms, allowing us to elucidate structurally and vibrationally relevant effects of the main intra- and intermolecular interactions operating in the different studied phases. Very interestingly, the observed UV-induced I → II rotamerization was found to take place in an exclusive basis, with no other photochemical processes being observed to occur upon UV irradiation, under the experimental conditions used in the present investigation.

Synthesis of Cyclic Fragrances via Transformations of Alkenes, Alkynes and Enynes: Strategies and Recent Progress.

With increasing demand for customized commodities and the greater insight and understanding of olfaction, the synthesis of fragrances with diverse structures and odor characters has become a core task. Recent progress in organic synthesis and catalysis enables the rapid construction of carbocycles and heterocycles from readily available unsaturated molecular building blocks, with increased selectivity, atom economy, sustainability and product diversity. In this review, synthetic methods for creating cyclic fragrances, including both natural and synthetic ones, will be discussed, with a focus on the key transformations of alkenes, alkynes, dienes and enynes. Several strategies will be discussed, including cycloaddition, catalytic cyclization, ring-closing metathesis, intramolecular addition, and rearrangement reactions. Representative examples and the featured olfactory investigations will be highlighted, along with some perspectives on future developments in this area.

Lipase-active heterogeneous biocatalysts for enzymatic synthesis of short-chain aroma esters

The lipase-active heterogeneous biocatalysts were prepared by adsorptive immobilization of Thermomyces lanuginosus lipase (designated as rPichia/lip) produced by authoring recombinant Pichia pastoris strain. Biocatalysts of LipoCarb type were prepared by spontaneous adsorption of rPichia/lip on the authoring macroporous carbon aerogel. Biocatalysts of LipoSil type were prepared by forced adsorption of rPichia/lip on mesoporous silica. The prepared biocatalysts were studied carefully in the esterification of short-chain fatty acids (butyric C4, C5–C7) and aliphatic alcohols (ethanol C2, C3–C5, C8) in order to produce valuable fruity-smelling esters. Biocatalytic properties, such as enzymatic activity, substrates specificity, and operational stability, were found to depend on chemical nature of both the adsorbents and organic solvents, primarily on their polarity. When comparing the activity in the synthesis of n-butyl heptanoate, it was found that the LipoCarb biocatalysts demonstrated activity an order of magnitude higher than LipoSil type. The Michaelis-Menten kinetic constants differed by a factor of 30, e.g. 1.1·102 s−1 and 3.7 s−1, respectively. The operational stability of the lipase-active biocatalysts was sufficiently high; rPichia/lip adsorbed on carbon aerogel retained till 96% of the initial activity after 29 reaction cycles, whereas rPichia/lip adsorbed on silica completely retained the activity after 38 reaction cycles of esterification under optimal reaction conditions selected. The prepared biocatalysts of LipoCarb and LipoSil types were promising for the Green enzymatic synthesis of fragrance and aroma esters under very mild ambient conditions (20±2 °C, 1 bar).

Metabolic Engineering of Escherichia coli for High-Yield Production of (R)-1,3-Butanediol.

1,3-Butanediol (1,3-BDO) is an important C4 platform chemical widely used as a solvent in cosmetics and a key intermediate for the synthesis of fragrances, pheromones, and pharmaceuticals. The development of sustainable bioprocesses to produce enantiopure 1,3-BDO from renewable bioresources by fermentation is a promising alternative to conventional chemical routes and has aroused great interest in recent years. Although two metabolic pathways have been previously established for the biosynthesis of (R)-1,3-PDO, the reported titer and yield are too low for cost-competitive production. In this study, we report the combination of different metabolic engineering strategies to improve the production of (R)-1,3-BDO by Escherichia coli, including (1) screening of key pathway enzymes; (2) increasing NADPH supply by cofactor engineering; (3) optimization of fermentation conditions to divert more flux into 1,3-BDO pathway; (4) reduction of byproducts formation by pathway engineering. With these efforts, the best engineered E. coli strain can efficiently produce (R)-1,3-BDO with a yield of 0.6 mol/mol glucose, corresponding to 60% of the theoretical yield. Besides, we also showed the feasibility of aerobically producing 1,3-BDO via a new pathway using 3-hydroxybutyrate as an intermediate.

An Overview of Biotransformation and Toxicity of Diterpenes.

Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest in developing methods to obtain derivatives of these compounds, and biotransformation processes are interesting tools for the structural modification of natural products with complex chemical structures. Biotransformation processes also have a crucial role in drug development and/or optimization. The understanding of the metabolic pathways for both phase I and II biotransformation of new drug candidates is mandatory for toxicity and efficacy evaluation and part of preclinical studies. This review presents an overview of biotransformation processes of diterpenes carried out by microorganisms, plant cell cultures, animal and human liver microsomes, and rats, chickens, and swine in vivo and highlights the main enzymatic reactions involved in these processes and the role of diterpenes that may be effectively exploited by other fields.

Unravelling transition metal-catalyzed terpenic alcohol esterification: a straightforward process for the synthesis of fragrances

Iron nitrate, a simple and commercially available Lewis acid, catalyzes terpenic alcohol esterification with acetic acid, achieving high conversion and ester selectivity.

Sn(ii)-catalyzed β-citronellol esterification: a Brønsted acid-free process for synthesis of fragrances at room temperature

Simple SnCl2·2H2O was demonstrated to be able to catalyze β-citronellol esterification with acetic acid at room temperature under solvent-free conditions, achieving high conversion and ester selectivity (ca. 88% and 99%, respectively).

H- and Fe-modified zeolite beta catalysts for preparation of trans-carveol from α-pinene oxide

The isomerisation of α-pinene oxide has been intensively investigated for selective preparation of campholenic aldehyde, a compound used in the synthesis of fragrances. Selective preparation of another product of α-pinene oxide rearrangement, trans-carveol, still remains a challenging task. Trans-carveol is a highly valuable compound used in perfume bases, food flavour compositions and as an active pharmaceutical substance in chemoprevention of mammary carcinogenesis.In the present work zeolite beta with different SiO2/Al2O3 molar ratios was modified by iron, characterised and tested per se and in the modified form for trans-carveol preparation from α-pinene oxide. The isomerisation reaction was carried out in a polar basic solvent N,N-dimethylacetamide at 140°C. The activities and selectivities of the catalysts were correlated with their acid properties and with the iron content.

Synthesis of Fragrance 1-(3,3-dimethylcyclohexyl)Ethyl Acetate

1-(3,3-dimethylcyclohexyl) ethyl acetate was synthesized by the reaction of dihydromycene with acetic acid in the presence of sulfuric acid. The effecting factors including the amount of catalyst, the reaction temperature, the molar ratio of raw materials and the reaction time were investigated. The experimental results showed that the molar raio of the dihydromyrcene to acetic acid to sulfuric acid was 1:3:0.2, the reaction temperature is 60 °C and the reaction time was 6.5 h. The yield reached 45.3%. The structure of product was characterized by gas chromatography, mass spectrometry, infrared spectroscopy and nuclear magnetic resonance. The odor evaluation result indicated that the product had a sweet, woody, floral odor.

A Highly Stereoselective Organocatalytic Approach to Lilial® and Muguesia

The stereoselective alkylation of aldehydes with benzodithiolylium tetrafluoborate gave a straightforward access to key compounds for the synthesis of fragrances and flavors.

Recent Advances in the Synthesis of Fragrances

Recent Advances in the Synthesis of Fragrances

Mesoporous niobosilicates serving as catalysts for synthesis of fragrances

Niobium-containing siliceous-MSU-X mesoporous molecular sieves have been prepared according to an original pathway by the reaction between low-cost niobium species (ammonium trisoxalate complex of niobium (V)), silica precursor (tetraethyl orthosilicate), and biodegradable surfactant in strong acidic, acidic or almost neutral medium. The selective oxidation of several terpenes and terpenoids (geraniol, limonene, α-terpineol) using hydrogen peroxide as an oxidant agent over novel Nb-catalysts is studied in this work. A variety of (Nb)MSU-X and (Ru,Nb)MSU-X materials prepared under different conditions has been employed (supermicroporous/mesoporous molecular sieves) for this purpose. The structure–function relationships in these catalysts are reported.

Heterogeneous Palladium Catalysts for a New One‐Pot Chemical Route in the Synthesis of Fragrances Based on the Heck Reaction

AbstractThe one‐pot synthesis of the fragrance 4‐(p‐methoxyphenyl)butan‐2‐one, with raspberry scent, has been carried out using palladium on different supports such as magnesium oxide (MgO), hydrotalcite, hydroxyapatite (HA), aluminium oxide (γ‐Al2O3) and titanium dioxide (TiO2). The first pathway consists of a Heck coupling between 4‐methoxyiodoanisole and methyl vinyl ketone followed by hydrogenation. Palladium supported on titanium dioxide showed the best performance for carrying out both consecutive steps giving 4‐(p‐methoxyphenyl)butan‐2‐one with high yields and selectivity. The Pd‐TiO2 catalyst is more active than a homogeneous palladium complex that is well accepted in the literature as being highly active for performing Heck reactions.

Synthesis of fragrance and flavour grade esters: activities of different ion exchange resins and kinetic studies

Esters are very valuable chemicals used in the fragrance, flavour, pharmaceutical, dyestuff and plastic industries. Several synthetic routes exist to make esters, but the carboxylic acid–alcohol reaction is the most common for which homogeneous, polluting and corrosive acids are used as catalysts. Perfumery and flavour grade esters need to be free of inorganic impurities and colouration. The current work has evaluated the activity of ion exchange resin catalysts for the synthesis of methyl salicylate and methyl anthranilate, methyl-4-hydroxy benzoate from the respective carboxylic acid and methanol.