Synthesis and Olfactory Properties of Seco-Analogues of Lilac Aldehydes.

Lilac aldehydes are considered as principal olfactory molecules of lilac flowers. We have designed, prepared, and evaluated a set of racemic seco-analogues of such natural products. The synthesis employs commercially available α-chloroketones as substrates that are transformed in four steps to target compounds. Their qualitative olfactory analysis revealed that the opening of the tetrahydrofuran ring leads to a vanishing of original flowery scent with the emergence of spicy aroma accompanied by green notes, and/or fruity aspects of novel seco-analogues. These results suggest the important osmophoric role of THF moiety for the generation of the typical flowery aroma associated with lilac aldehydes.

Polyradical PROXYL/TEMPO Conjugates Connected by Ester/Amide Bridges: Synthesis, Physicochemical Studies, and DFT Calculations.

A series of di-/trinitroxide esters and amides featuring PROXYL and/or TEMPO radicals connected with alicyclic bridges were prepared in 61-92 % yields and their properties were analysed by using multiple experimental techniques. The examination of EPR spectra of radicals in organic solvents augmented with DFT calculations brought valuable information on the conformational dynamics and spin exchange mechanisms. Cyclic voltammetry investigations revealed (quasi)reversible electrochemical behaviour of studied nitroxides with their half-wave potentials ranging from -51 to -17 mV. SQUID measurements of selected radicals revealed that the magnetism of di- and trinitroxides is significantly different, since antiferromagnetic coupling in biradicals is notably larger than in triradicals. The single-crystal X-ray analysis of selected biradicals revealed the existence of 3D supramolecular networks of molecules linked through hydrogen-bonding interactions. These polynitroxide radicals can serve as promising bridging or chelating ligands in the synthesis of transition-metal-based molecular magnets.

Scalable Green Approach Toward Fragrant Acetates.

The advantageous properties of ethylene glycol diacetate (EGDA) qualify it as a useful substitute for glycerol triacetate (GTA) for various green applications. We scrutinised the lipase-mediated acetylation of structurally diverse alcohols in neat EGDA furnishing the range of naturally occurring fragrant acetates. We found that such enzymatic system exhibits high reactivity and selectivity towards activated (homo) allylic and non-activated primary/secondary alcohols. This feature was utilised in the scalable multigram synthesis of fragrant (Z)-hex-3-en-1-yl acetate in 70% yield. In addition, the Lipozyme 435/EGDA system was also found to be applicable for the chemo-selective acetylation of (hydroxyalkyl) phenols as well as for the kinetic resolution of chiral secondary alcohols. Lastly, its discrimination power was demonstrated in competitive experiments of equimolar mixtures of two isomeric alcohols. This enabled the practical synthesis of 1-pentyl acetate isolated as a single product in 68% yield from the equimolar mixture of 1-pentanol and 3-pentanol.

Scalable Preparation of Enantioenriched (S)-5-methylhept-2-en-4-one. Synthesis and Aroma Properties of Achiral Analogues Thereof.

(S)-5-Methylhept-2-en-4-one is a key flavour compound in hazelnuts. We have performed its chiral-pool-based chemoenzymatic synthesis with 39% overall yield (73% ee). The four-step aldol-based sequence avoids the use of highly reactive and/or toxic reagents, does not require anhydrous conditions and uses only distillation as the purification method. Thus, such methodology represents a green and scalable alternative to only two stereoselective approaches towards this natural product known so far. In addition, we have designed and prepared a set of new (di)enones as achiral synthetic analogues of the title compound. The results of their sensory analyses clearly show that relatively minor structural changes of the natural molecule significantly alter its olfactory properties. Thus, simple (poly)methylation completely changes the original hazelnut aroma of (S)-5-methylhept-2-en-4-one and shifts the odour of its analogues to eucalyptus, menthol, camphor, and sweet aroma.

Filbertone: A Review.

This comprehensive review of filbertone, a principal flavor compound of hazelnut, evaluates the current state of the art of all relevant aspects of the title molecule: its occurrence and properties, laboratory preparation and bulk synthesis, analytical issues regarding stereochemistry and purity, sensory evaluation, and practical uses. Comparisons are made between different synthetic approaches, and a critical assessment of various applications is presented.

Polyradical PROXYL/TEMPO-Derived Amides: Synthesis, Physicochemical Studies, DFT Calculations, and Antimicrobial Activity.

A series of polynitroxide amides possessing 2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PROXYL) and/or 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) units connected through various bridges were synthesized and their properties were analyzed. EPR spectroscopy provided detailed insight into their paramagnetic character and related properties. A thorough examination of the EPR spectra of dinitroxides in organic solvents provided valuable information on the intramolecular motions, thermodynamics, and spin-exchange mechanisms. Analysis of low-temperature X- and Q-band EPR spectra of the dissolved dinitroxides provided spin-spin distances that were comparable with the theoretical values obtained by DFT. Cyclic voltammetry investigations revealed (quasi)reversible electrochemical behavior for PROXYL-derived biradicals, whereas significant loss of the reversibility was found for TEMPO-containing bi- and polyradicals. The inhibitory activities of the nitroxides against model bacteria, yeasts, and filamentous fungi were assessed.

Synthesis, physicochemical properties and antimicrobial activity of mono-/dinitroxyl amides.

Two comparative sets of mono-/dinitroxyl amides were designed and prepared. The novel TEMPO and/or PROXYL derivatives were fully characterised and their spin, redox and antimicrobial properties were determined. Cyclic voltammetry revealed (quasi)reversible redox behavior for most of the studied radicals. Moreover, the electron-withdrawing substituents increased the oxidation potential of nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals featured the typical three-line signal, the spectra of biradicals showed more complex splitting patterns. The in vitro biological assay revealed that unlike pyrrolidinyl derivatives, the piperidinyl nitroxides significantly inhibited the growth of Staphylococcus sp.

The determination of botanical origin of honeys based on enantiomer distribution of chiral volatile organic compounds.

The enantiomer ratios of chiral volatile organic compounds in rapeseed, chestnut, orange, acacia, sunflower and linden honeys were determined by multi-dimensional gas chromatography using solid phase microextraction (SPME) as a sample pre-treatment procedure. Linalool oxides, linalool and hotrienol were present at the highest concentration levels, while significantly lower amounts of α-terpineol, 4-terpineol and all isomers of lilac aldehydes were found in all studied samples. On the other hand, enantiomer distribution of some chiral organic compounds in honey depends on their botanical origin. The significant differences in enantiomer ratio of linalool were observed for rapeseed honey that allows us to distinguish this type of honey from the other ones. The enantiomer ratios of lilac aldehydes were useful for distinguishing of orange and acacia honey from other studied monofloral honeys. Similarly, different enantiomer ratio of 4-terpineol was found for sunflower honeys.

Preparation and spectroscopic, magnetic, and electrochemical studies of mono-/biradical TEMPO derivatives.

A comparison set of mono-/biradical TEMPO derivatives was prepared, novel compounds were fully characterized, and their physicochemical properties were determined. Cyclic voltammetry revealed reversible redox behavior for all studied nitroxides. Moreover, the electron-withdrawing substituents increased the oxidation potential of the respective nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals in dichloromethane at 295 K reveal the expected three-line signal, spectra of biradicals show more complex features. DFT and MP2 calculations indicate that the EPR splitting pattern of dinitroxide 7 could be explained by its interactions with solvent molecules. In the solid state, mononitroxides 4 and 5 behave as a Heisenberg antiferromagnetic chain, whereas dinitroxides 6-8 are almost isolated paramagnetic diradicals coupled in an antiferromagnetic manner.

Bismuth(III) triflate promoted intramolecular hydroamination of unactivated alkenyl sulfonamides in the preparation of pyrrolidines.

Bi(OTf)(3)·nH(2)O was found to be an efficient promoter of the cyclisative hydroamination of unactivated alkenyl sulfonamides, giving rise to the N-protected 2-methyl pyrrolidines in good to excellent yields (up to 95%). Based on control experiments, a joint Lewis acid-Brønsted acid catalysis might be in operation, or triflic acid itself, generated in situ by hydrolysis of metal triflate, could be the true hydroamination catalyst.

Efficient total synthesis of (+)-dihydropinidine, (-)-epidihydropinidine, and (-)-pinidinone.

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (-)-epidihydropinidine (2) (as HCl salts), and (-)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker-Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1-3). The first single-crystal X-ray analysis of (-)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.

Novel Pd(II)-catalysed N,O-bicyclisation as an efficient route to the 6-oxa-2-azabicyclo[3.2.1]octane skeleton.

1-(Benzyloxycarbonylamino)-hex-5-en-3-ol undergoes a novel Pd(II)/CuCl2-catalysed bicyclisation to furnish the corresponding 6-oxa-2-azabicyclo[3.2.1]octane in good yield.