Chemical and Olfactory Analysis of the Volatile Fraction of Ocimum gratissimum Concrete from Madagascar.

The chemical composition of the volatile fraction of Ocimum gratissimum concrete (romba) from Madagascar has been determined for the first time by GC/MS and GC-FID. A methyl cinnamate chemotype has been determined for this material, along with a set of compounds typical in essential oils and extracts from plants of the Ocimum genus. Variability was mostly observed on terpenes and terpenoids components. GC-O-MS was also used for a sensory evaluation of this material performed by a master perfumer. The chemical composition of this O. gratissimum extract was then compared with literature data to assess subtle differences between chemotypes of the same species and other species of the same genus within natural variability. A mapping illustrates the occurrence of the cinnamate chemotype in Eastern Africa, India and now Madagascar, while other origins generally present eugenol, thymol, camphor, or linalool chemotypes.

Spirocyclic Compounds in Fragrance Chemistry: Synthesis and Olfactory Properties.

In this Review, both the scientific literature and patents have been analysed to gather, examine and classify synthetic strategies developed to access spirocyclic molecules having olfactory properties of interest for the perfume industry. New structures have been reported at a steady state since 1961 with a particularly intense activity in the 80's. In the diversity of olfactory properties observed, spirocyclic molecules were found to be quite frequently woody, as well as fruity and ambery, among other tonalities. More recent data reflect the evolution of modern synthetic organic chemistry towards bioinspiration, enantioselective reactions, green and sustainable chemistry and biotechnology.

Laccase-Catalyzed Oxidation of Allylbenzene Derivatives: Towards a Green Equivalent of Ozonolysis.

Laccase-based biocatalytic reactions have been tested with and without mediators and optimized in the oxidation of allylbenzene derivatives, such as methyl eugenol taken as a model substrate. The reaction primarily consisted in the hydroxylation of the propenyl side chain, either upon isomerization of the double bond or not. Two pathways were then observed; oxidation of both allylic alcohol intermediates could either lead to the corresponding α,ß-unsaturated carbonyl compound, or the corresponding benzaldehyde derivative by oxidative cleavage. Such a process constitutes a green equivalent of ozonolysis or other dangerous or waste-generating oxidation reactions. The conversion rate was sensitive to the substitution patterns of the benzenic ring and subsequent electronic effects.

Type and magnitude of non-compliance and adulteration in neroli, mandarin and bergamot essential oils purchased on-line: potential consumer vulnerability.

Thirty-one samples of essential oils used both in perfumery and aromatherapy were purchased to business-to-consumers suppliers and submitted to standard gas chromatography-based analysis of their chemical composition. Their compliance with ISO AFNOR standards was checked and revealed, although ISO AFNOR ranges are relatively loose, that more than 45% of the samples analyzed failed to pass the test and more than 19% were diluted with solvents such as propylene and dipropylene glycol, triethyl citrate, or vegetal oil. Cases of non-compliance could be due to substitution or dilution with a cheaper essential oil, such as sweet orange oil, blending with selected compounds (linalool and linalyl acetate, maybe of synthetic origin), or issues of aging, harvest, or manufacturing that should be either deliberate or accidental. In some cases, natural variability could be invoked. These products are made available to the market without control and liability by resellers and could expose the public to safety issues, in addition to commercial prejudice, in sharp contrast with the ever-increasing regulations applying to the sector and the high demand of consumers for safe, controlled and traceable products in fragrances and cosmetic products.

Chemistry, Sustainability and Naturality of Perfumery Biotech Ingredients.

Invited for this month's cover is the group of Sylvain Antoniotti at the University Côte d'Azur. The image shows a perfume dispenser containing bacterial cells delivering odorants molecules with a wide diversity and complexity of structures and olfactory notes. The person wears an art nouveau pendant featuring an enzyme and is peacefully hanging in a green and floral landscape. The Minireview itself is available at 10.1002/cssc.202001661.

Chemistry, Sustainability and Naturality of Perfumery Biotech Ingredients.

White biotechnology has emerged in biochemical manufacturing processes to deliver perfumery ingredients satisfying interests of the society for natural, eco-responsible, and sustainable materials. As a result, an intense R&D activity has taken place on these subjects, resulting in both scientific publications and patent applications reporting combinations of state-of-the-art approaches in biocatalysis, metabolic engineering, synthetic biology, biosynthesis elucidation, gene edition and cloning, and analytical chemistry. In this Minireview, a smelly selection of novel biotechnological processes and ingredients from a scientific articles and patents survey covering the last 6 years is presented and analysed in terms of chemistry, sustainability and naturality. Classification has been made between metabolic engineering on one side, allowing either biotechnological synthesis of essential oil surrogates or single molecule ingredients, and on the other side the optimisation of properties of natural complex substances by specific and selective enzymatic modifications of their chemical composition.

Unusual Polycyclic Fused Product by Oxidative Enzymatic Dimerisation of 5-methylpyrogallol Catalysed by Horseradish Peroxidase/H2O2.

During investigations on the peroxidase-catalysed oxidation of polyhydroxylated monoaromatic substrates such as 5-methylpyrogallol, we observed a spectacular dimerisation proceeding by dearomatisation in contrast with most common reaction patterns involving phenolics oxidation and dimerization. A tetracyclic fused product featuring an unusual 2-oxatetracyclo [6.3.1.01,6.04,12] dodecan-3-one core was obtained and characterized by combined NMR techniques and high resolution mass spectroscopy (HRMS). This is an example of a spontaneous cascade triggered by a simple enzymatic reaction that could provide new options for biosynthetic hypothesis and a synthetic method to access this complex core in one operation.

Sustainable Manufacture of a Valuable Fragrance Ingredient: Lipase-Catalyzed Acylation of Vetiver Essential Oil and Chemoselectivity between Sesquiterpene Alcohols.

A lipase-catalyzed acylation reaction of crude Haitian vetiver essential oil was studied as an alternative to chemical processes for the manufacture of an industrially relevant fragrance ingredient. A competitive process that involved a recyclable immobilized lipase at 10 % w/w was developed and used up to the kilogram scale and quantitatively delivered the target product with good productivity (up to 90 g L-1 h-1 ). With the support of comprehensive two-dimensional gas chromatography/mass spectrometry (GC×GC-MS), it was found that the enzymatic reaction exhibited a high chemoselectivity in favor of primary sesquiterpene alcohols. This finding and its consequence on the olfactory properties were correlated with sensory analysis.

Enolizable Carbonyls and N,O-Acetals: A Rational Approach for Room-Temperature Lewis Superacid-Catalyzed Direct α-Amidoalkylation of Ketones and Aldehydes.

An efficient catalytic room-temperature direct α-amidoalkylation of carbonyl donors, that is, ketones and aldehydes with unbiased N,O-acetals, is described. Sn(NTf2 )4 is an optimal catalyst to promote this challenging transformation at low loading and the reaction shows promising scope. A comprehensive and rational evaluation of this reaction has led to the establishment of an empirical scale of nucleophilic reactivity for a broad set of ketones that should be helpful in the synthetic design and development of carbonyl α-functionalization methods.

Tuning of essential oil properties by enzymatic treatment: towards sustainable processes for the generation of new fragrance ingredients.

In this review, several strategies of modification of essential oils by enzymatic treatment are presented. Being either applied before or after the production of the essential oil, enzymatic methods are shown to be particularly adapted to attain the required selectivity, specificity and efficiency in sustainable processes delivering products eligible for the natural grade. Examples dealing with the optimization of the properties of essential oils in terms of biological activity, odor and safety are provided, and it is likely that these strategies will address other type of properties in the future, such as the physico-chemical properties, for example.

Secondary metabolites isolation in natural products chemistry: comparison of two semipreparative chromatographic techniques (high pressure liquid chromatography and high performance thin-layer chromatography).

Chemical investigations on secondary metabolites in natural products chemistry require efficient isolation techniques for characterization purpose as well as for the evaluation of their biological properties. In the case of phytochemical studies, the performance of the techniques is critical (resolution and yield) since the products generally present a narrow range of polarity and physicochemical properties. Several techniques are currently available, but HPLC (preparative and semipreparative) is the most widely used. To compare the performance of semipreparative HPLC and HPTLC for the isolation of secondary metabolites in different types of extracts, we have chosen carvone from spearmint essential oil (Mentha spicata L.), resveratrol from Fallopia multiflora (Thunb.) Haraldson, and rosmarinic acid from rosemary (Rosmarinus officinalis L.) extracts. The comparison was based on the chromatographic separation, the purity and quantity of isolated compounds, the solvent consumption, the duration and the cost of the isolation operations. The results showed that semipreparative HPTLC can in some case offer some advantages over conventional semipreparative HPLC.

Enzymatic modification of palmarosa essential oil: chemical analysis and olfactory evaluation of acylated products.

We have developed an enzymatic protocol to modify the composition of palmarosa essential oil by acylation of its alcohol components by three different acyl donors at various rates. The resulting modified products were characterized by qualitative and quantitative analyses by gas chromatography, and their olfactory properties were evaluated by professional perfumers. We showed that our protocol resulted in two types of modifications of the olfactory properties. The first and most obvious effect observed was the decrease of the alcohol content, with the concomitant increase of the corresponding esters, along with their fruity notes (pear, most notably). The second and less obvious effect was the expression of notes from minor components ((E)-ß-ocimene, linalool, ß-caryophyllene, and farnesene), originally masked by the sweet-floral-rose odor of geraniol, present in 70% in the palmarosa essential oil used, and emergence of citrus, green, spicy and clove characters in the modified products. This methodology might be considered in the future as a sustainable route to new natural ingredients for the perfumer.

Experimental and theoretical studies on the bismuth-triflate-catalysed cycloisomerisation of 1,6,10-trienes and aryl polyenes.

Cycloisomerisation of polyenes such as diethyl geranylprenylmalonate [(E)-1 a], diethyl geranylphenylmalonate [(E)-2 a] and diethyl cinnamylgeranylmalonate [(E,E)-3 a] catalysed by bismuth triflate was studied from experimental and theoretical viewpoints. Several intermediates were isolated and characterised, and calculated transition-state structures are proposed for the three reactions. The diastereoselectivity observed during the reaction of (E)- or (Z)-2 a in favour of the formation of trans-fused bicyclic products is discussed in detail. The nature of the active catalytic species derived from bismuth triflate was also investigated, and the formation of a hybrid Lewis acid/Brønsted acid catalyst with water molecules is proposed, supported by experimental and theoretical data.

Model study of the enzymatic modification of natural extracts: peroxidase-based removal of eugenol from rose essential oil.

A protocol based on the use of horseradish peroxidase (HRP) is proposed for the removal of allergenic eugenol from rose essential oil without loss of the organoleptic quality and with a good conservation of the chemical composition. For the first time, an enzyme-based strategy is proposed for essential oils treatment and opens new opportunities in the detoxification of natural extracts used in perfumery and cosmetics. Our results on eugenol in rose essential oil constitute a first step toward the development of efficient and mild processes for the removal of more toxic compounds of natural extracts.

Valuable chemicals by the enzymatic modification of molecules of natural origin: terpenoids, steroids, phenolics and related compounds.

A renewed interest for using natural organic molecules for the production of valuable chemicals is observed in current organic processes. Natural compounds provide the access to natural grade chemicals when submitted to physical treatments or biotechnological processes. Dealing with structurally complex molecules, they can provide complex core structures for hemisynthesis purposes, and in many instances they offer the advantage of providing sustainable processes when using renewable resources. These assets could be synergistic with the assets of biocatalytic processes, to end-up with efficient and sustainable processes in the organic synthesis of valuable products. In this review, we have gathered a selection of examples on the use of enzymes for the modification of molecules of natural origin being either purified compounds (terpenoids, steroids, phenolics) or mixtures (essential oils, natural extracts) to access fine chemicals or organic polymers.

Biomimetic cationic polyannulation reaction catalyzed by Bi(OTf)3: cyclization of 1,6-dienes, 1,6,10-trienes, and aryl polyenes.

Nonactivated trienes and aryltrienes were cyclized into polycyclic compounds in good to excellent yields under bismuth triflate catalysis in a biomimetic fashion. The reaction showed broad applicability and allowed for the formation of functionalized bicyclic to tetracyclic structures from simple precursors in one pot. For some specific substrates, the cyclization was followed by a methyl shift as encountered in terpenoid biosynthesis.

Metal triflimidates: better than metal triflates as catalysts in organic synthesis--the effect of a highly delocalized counteranion.

The continuously increasing need for novel and selective methods in organic synthesis to aid drug discovery and to address environmental concerns is a constant source of stimulation to develop novel and more efficient reaction systems. This has often resulted in a focus on transition metals, ligands, and additives, with much less attention paid to the counterion(s) of the metal cation. Recently, metal salts with one or more triflimidate counterion(s) have appeared as a unique class of catalysts that display outstanding σ- and π-Lewis acid character. The highly delocalized nature of the triflimidate counterion, combined with its high steric hindrance results in virtually no nucleophilic behavior and an extremely high positive charge density on the metal cation, thus enhancing its Lewis acid character. Consequently, these metal triflimidates often outperform their metal halide or triflate analogues. This Review describes general methods for the preparation of metal triflimidate salts and their use as catalysts.

Facile preparation of metallic triflates and triflimidates by oxidative dissolution of metal powders.

Various metallic triflates and triflimidates were prepared by the straightforward oxidative dissolution of the corresponding metal powder in DMSO under an atmospheric pressure of O2 in the presence of stoichiometric amounts of triflic or triflimidic acid.

Apocynin derivatives interrupt intracellular signaling resulting in decreased migration in breast cancer cells.

Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics.