Odds and Trends: Recent Developments in the Chemistry of Odorants

Fragrance chemistry is, together with the closely related area of flavor chemistry, one of the few domains, if not the only one, in which chemists can immediately experience structure–activity relationships. This review presents structure–odor correlations and olfactophore models for the main odor notes of perfumery: “fruity”, “marine”, “green”, “floral”, “spicy”, “woody”, “amber”, and “musky”. New trendsetters and so‐called captive odorants of these notes are introduced, and recent activities and highlights in fragrance chemistry are summarized. The design of odorants, their chemical synthesis, and their use in modern perfumery is discussed. Our selection is guided and illustrated by creative fragrances, and features new odorants which encompassed current trends in perfumery. New odorants for grapefruit and blackcurrant, for galbanum, and leafy top notes are presented. Compounds with fashionable marine, ozonic, and aquatic facets are treated, as well as new odorants for classical lily‐of‐the‐valley, rose, and jasmine accords. Compounds with sweet and spicy tonalities are also discussed, as are the most recent developments for woody notes such as sandalwood and vetiver. We conclude with musky and ambery odorants possessing uncommon or unusual structural features. Some odor trends and effects are illustrated by microencapsulated fragrance samples, and areas where there is need for the development of new synthetic materials and methodologies are pointed out. Thus, chemists are invited to explore fragrance chemistry and participate in the design and synthesis of new odorants. This review gives the latest state of the art of the subject.     

NOP – Ein neues organischchemisches Grundpraktikum: Nachhaltigkeit per Internet

The sustainable organic chemistry lab course for the new milennium (NOP) makes use of the possibilities that an interactive website provides compared to a conventional lab course published as a textbook or manual. The prospective synthetic chemist can thus gain a more in‐depth understanding of his/her experiments. Detailed information about analytical methods, background information about the sub‐ stances being used and being formed during the experiment and “management ratios” like substance efficiency and energy efficiency are provided. Last but not least, knowledge about the concept “sustainable development” is being adapted to the domain of synthetic chemistry.     

Quadratisch,praktisch, natürlich?

In 2013 the consumer group Stiftung Warentest conducted tests on nut containing chocolates and detected piperonal (heliotropine) in Ritter‐Sport's “Voll‐Nuss” (whole hazelnut). Stiftung Warentest concluded that piperonal could not be obtained naturally and that Ritter‐Sport misled consumers by falsely labelling it as “natural flavor.” Ritter said the allegations were “baseless” and went to court. During the court case, Ritter's flavor supplier Symrise AG guaranteed that the “natural” piperonal was manufactured “naturally” according to the European flavor regulations. Ritter‐Sport had “won” the “German chocolate battle.” Although the full manufacturing process has not been revealed during the court case, there are many hints in the scientific and patent literature that piperonal can be indeed produced naturally in accordance with the European flavor regulations.     

Mechanical and Chemical Explanations in Du Clos' Chemistry

Abstract

Samuel Cottereau Du Clos (1598–1685) appears as the first French chemist to combine in chemistry (for him, the science of substances, the physics of qualities) demonstrations using the laws of motion with demonstrations using the qualities of chemical principles. In this way, he brought to bear two different and complementary orders of explanation. According to Du Clos, the mechanical considerations represent a first approach, a stage towards the knowledge of “the truth of things” (la vérité des choses) in natural philosophy. He set out his chemistry at the Académie royale des sciences de Paris, especially through his criticism of Boyle's Certain Physiological Essays in 1668–1669.     

Anselme Payen (1795–1871), Learned Manufacturer of Chemical Products

Abstract

Between 1835 and 1871, Anselme Payen (1795-1871) taught industrial chemistry at both the Ecole centrale des arts et manufactures and the Conservatoire des arts et métiers. In addition, he held several administrative functions in such institutions as the Société d'encouragement pour l'industrie nationale and the Société centrale d'agriculture. Prior to 1835, however, he owned a chemical manufactory situated in the plain of Grenelle. This paper is about Payen's career as a chemical manufacturer (1815–1835) and his various innovation strategies. The themes discussed are the lead chamber process of sulfuric acid production, artificial borax as a substitute for refined Tibetan tincal, the decolourising power of boneblack, and the “export” of the knacker's trade to the countryside. Different forms of applied science can be seen at work here: analytical chemistry for chemical bookkeeping, laboratory-scale analysis of various manufacturing conditions, theoretical explanation, and the reconstruction of traditional practices. These various ways of applying science to manufacturing problems make Payen stand out as what Chaptal had called a fabricant éclairé.     

MaxSynBio: Avenues Towards Creating Cells from the Bottom Up

A large German research consortium mainly within the Max Planck Society (“MaxSynBio”) was formed to investigate living systems from a fundamental perspective. The research program of MaxSynBio relies solely on the bottom‐up approach to synthetic biology. MaxSynBio focuses on the detailed analysis and understanding of essential processes of life through modular reconstitution in minimal synthetic systems. The ultimate goal is to construct a basic living unit entirely from non‐living components. The fundamental insights gained from the activities in MaxSynBio could eventually be utilized for establishing a new generation of biotechnological processes, which would be based on synthetic cell constructs that replace the natural cells currently used in conventional biotechnology.     

Movies of Molecular Motions and Reactions: The Single‐Molecule,Real‐Time Transmission Electron Microscope Imaging Technique

“The truth is, the Science of Nature has been already too long made only a work of the Brain and the Fancy: It is now high time that it should return to the plainness and soundness of Observations on material and obvious things,” proudly declared Robert Hooke in his highly successful picture book of microscopic and telescopic images, “Micrographia” in 1665. Hooke’s statement has remained true in chemistry, where a considerable work of the brain and the fancy is still necessary. Single‐molecule, real‐time transmission electron microscope (SMRT‐TEM) imaging at an atomic resolution now allows us to learn about molecules simply by watching movies of them. Like any dream come true, the new analytical technique challenged the old common sense of the communities, and offers new research opportunities that are unavailable by conventional methods. With its capacity to visualize the motions and the reactions of individual molecules and molecular clusters, the SMRT‐TEM technique will become an indispensable tool in molecular science and the engineering of natural and synthetic substances, as well as in science education.     

Chemical Syntheses and Chemical Biology of Carboxyl Polyether Ionophores: Recent Highlights

A central goal of chemical biology is to develop molecular probes that enable fundamental studies of cellular systems. In the hierarchy of bioactive molecules, the so‐called ionophore class occupies an unflattering position in the lower branches, with typical labels being “non‐specific” and “toxic”. In fact, the mere possibility that a candidate molecule possesses “ionophore activity” typically prompts its removal from further studies; ionophores—from a chemical genetics perspective—are molecular outlaws. In stark contrast to this overall poor reputation of ionophores, synthetic chemistry owes some of its most amazing achievements to studies of ionophore natural products, in particular the carboxyl polyethers renowned for their intricate molecular structures. These compounds have for decades been academic battlegrounds where new synthetic methodology is tested and retrosynthetic tactics perfected. Herein, we review the most exciting recent advances in carboxyl polyether ionophore (CPI) synthesis and in addition discuss the burgeoning field of CPI chemical biology.     

Structures and mechanisms in chemical reactions: George A. Olah’s life-long search of chemistry

The Hungarian-born American chemistry Nobel laureate George A. Olah used superacids to give longer life to carbocations. He resolved a long-standing debate on reaction mechanism in organic chemistry and, more importantly, opened new vistas in hydrocarbon chemistry to produce hosts of new compounds. The concerted utilization of organic synthesis, physical techniques, and computational methods led to spectacular achievements in hydrocarbon chemistry. Olah has always been on the lookout for the practical applications of his discoveries in fundamental chemistry. He continued his research after his Nobel award and has worked out the idea, which he labeled “the methanol economy.” Olah’s example shows that a great researcher can also be a devoted and caring human being.     

“On‐Droplet” Chemistry: The Cycloaddition of Diethyl Azodicarboxylate and Quadricyclane

Sharpless and co‐workers previously studied the [2σ+2σ+2π] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called “on‐water” chemistry. We have examined the same reaction in aqueous microdroplets (ca. 5 μm diameter) and find that the cycloaddition reaction is accelerated even further (by a factor of 10²) compared to that of the “on‐water” reaction reported previously. The trends of acceleration in solvents other than water demonstrated by Sharpless and colleagues were replicated in the corresponding microdroplet experiments. We also find that DEAD reacts with itself to form a variety of hydrazine carboxylates and intercept intermediates of this reaction in microdroplets to validate a mechanism proposed herein. We suggest that “on‐droplet” chemistry, similar to “on‐water” chemistry, may be a general process of synthetic interest.     

Synthesis of polystyrene‐based random copolymers with balanced number of basic or acidic functional groups

Pairs of polystyrene‐based random copolymers with balanced number of pendant basic or acidic groups were synthesized utilizing the template strategy. The same poly[(4‐hydroxystyrene)‐ran‐styrene] was used as a template backbone for modification. Two different synthetic approaches for the functionalization were applied. The first one involved direct functionalization of the template backbone through alkylation of the phenolic groups with suitable reagents. The second modification approach was based on “click” chemistry, where the introduction of alkyne groups onto the template backbone was followed by copper‐catalyzed 1,3 cycloaddition of aliphatic sulfonate‐ or amine‐contaning azides. Both synthetic approaches proved to be highly efficient as evidenced by ¹H‐NMR analyses. The thermal properties were evaluated by differential scanning calorimetry and thermal gravimetric analyses and were influenced by the type of functionality and the modification method. The ether‐linked functional colopymers were thermally more stable than their “clicked” analogues. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2044–2052, 2010     

New Vistas in N‐Heterocyclic Silylene (NHSi) Transition‐Metal Coordination Chemistry: Syntheses,Structures and Reactivity towards Activation of Small Molecules

This account is a review on the synthesis and transition‐metal coordination chemistry of N‐heterocyclic silylenes (NHSi’s) over the last 20 years till the present time (2012). Recently, fascinating and novel synthetic methods have been developed to access transition‐metal–NHSi complexes as an emerging class of compounds with a wealth of intriguing reactivity patterns. The striking influence of coordinating NHSi’s to transition‐metal complex fragments affording different reactivities to the “free” NHSi is a connecting theme (“leitmotif”) throughout the review, and highlights the potential of these compounds which lie at the interface of contemporary main‐group and classical organometallic chemistry towards new molecular catalysts for small‐molecule activation.     

Bringing the Science of Proteins into the Realm of Organic Chemistry: Total Chemical Synthesis of SEP (Synthetic Erythropoiesis Protein)

Erythropoietin, commonly known as EPO, is a glycoprotein hormone that stimulates the production of red blood cells. Recombinant EPO has been described as “arguably the most successful drug spawned by the revolution in recombinant DNA technology”. Recently, the EPO glycoprotein molecule has re‐emerged as a major target of synthetic organic chemistry. In this article I will give an account of an important body of earlier work on the chemical synthesis of a designed EPO analogue that had full biological activity and improved pharmacokinetic properties. The design and synthesis of this “synthetic erythropoiesis protein” was ahead of its time, but has gained new relevance in recent months. Here I will document the story of one of the major accomplishments of synthetic chemistry in a more complete way than is possible in the primary literature, and put the work in its contemporaneous context.     

A novel approach to tag and identify geranylgeranylated proteins

A recently developed proteomic strategy, the “GG‐azide”‐labeling approach, is described for the detection and proteomic analysis of geranylgeranylated proteins. This approach involves metabolic incorporation of a synthetic azido‐geranylgeranyl analog and chemoselective derivatization of azido‐geranylgeranyl‐modified proteins by the “click” chemistry, using a tetramethylrhodamine‐alkyne. The resulting conjugated proteins can be separated by 1‐D or 2‐D and pH fractionation, and detected by fluorescence imaging. This method is compatible with downstream LC‐MS/MS analysis. Proteomic analysis of conjugated proteins by this approach identified several known geranylgeranylated proteins as well as Rap2c, a novel member of the Ras family. Furthermore, prenylation of progerin in mouse embryonic fibroblast cells was examined using this approach, demonstrating that this strategy can be used to study prenylation of specific proteins. The “GG‐azide”‐labeling approach provides a new tool for the detection and proteomic analysis of geranylgeranylated proteins, and it can readily be extended to other post‐translational modifications.     

C?H Activation: A Complementary Tool in the Total Synthesis of Complex Natural Products

The recent advent of transition‐metal mediated C? H activation is revolutionizing the synthetic field and gradually infusing a “C? H activation mind‐set” in both students and practitioners of organic synthesis. As a powerful testament of this emerging synthetic tool, applications of C? H activation in the context of total synthesis of complex natural products are beginning to blossom. Herein, recently completed total syntheses showcasing creative and ingenious incorporation of C? H activation as a strategic manoeuver are compared with their “non‐C? H activation” counterparts, illuminating a new paradigm in strategic synthetic design.     

Julius Adolph Stöckhardt. Zum 200. Geburtstag

Julius Adolph Stoeckhardt, who was trained as a pharmacist and later worked as a chemist, left his marks in many fields. The intention of his action was the use of chemical knowledge in practice. Stoeckhardt was most important in helping to popularize agricultural chemistry, thanks to his endeavor agricultural experimental stations were established. He investigated fume gases and its influence on the forest and the toxicity of colors, carried out many chemical analyzes – also of rocks. He thought on methods of a successful teaching of natural science and fought for the recognition of chemistry as a common instrument for education. In memory of this scientist several institutions bear his name: e.g. a 1885 constructed laboratory building of the former Forest Academy in Tharandt, which in our days belongs to the Technical University of Dresden, Department of Forest, Geo‐ and Hydrosciences, a chemistry‐club for pupils in Chemnitz, who are interested in chemistry, a competition of pupils in Chemistry and an annual colloquium on environmental chemistry at Chemnitz Technical University.     

Hybrid linear dendritic macromolecules: From synthesis to applications

Linear‐dendritic copolymers are intriguing macromolecules, which offer challenge and fascination as purely synthetic objects at the crossroad of organic and polymer chemistry and as promising materials for diverse advanced applications. This review traces their discovery and highlights the synthetic strategies used for their construction. The ambivalent character of the linear‐dendritic architecture opens numerous avenues towards emerging and potential applications. Specific solution properties enable the construction of nanometer‐sized nanoreactors for reactions in environmentally friendly media, and the creation of “nanosponges” for selective passive binding of fluorescent pH‐indicators for environmental or biomonitoring. Another structure–property relationship is used for noncovalent and site‐specific modification of glycoproteins, which leads to the formation of “semiartificial” enzymes with enhanced and broadened catalytic activity. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5295–5314, 2008     

Piperidine‐Promoted Three‐Component Condensation: Synthesis of Chromene Heterocycles and Pyrazolotriazoles

Chromenes, the oxygen‐containing heterocyclic compounds, have a “special” place in biologically active natural products and in synthetic chemistry and in the fields of medicinal, agrochemical, cosmetic, and pigment industries. In this work, piperidine was used as a base catalyst for the convenient synthesis of 1,4‐dihydropyrano[2,3‐c ]pyrazole, 5,10‐dihydro‐4H‐benzo[g ]chromene, and pyrazolo[1,2‐a ] [1,2,4]triazole derivatives at ambient temperature. This methodology has several advantages including the use of easily accessible and inexpensive catalysts, short reaction times, high yields, convenient work‐up, and not needing column chromatography.     

4-Oxo-2-cyclopentenyl Acetate—A Synthetic Intermediate

The present day importance of cyclopentenone derivatives in preparative organic chemistry and especially in natural product chemistry is demonstrated by the stereoselective synthesis of substituted and annelated cyclopentanone derivatives. It has been found that 4-oxo-2-cyclopentenyl acetate (“4-acetoxy-2-cyclopenten-1-one”) can be used in many reactions as a substitute for cyclopentadienone, which is itself too unstable to be isolated. A large variety of polyfunctionalized cyclopentanone derivatives, as well as carbocyclic and heterocyclic annelation products, can thus be obtained in a simple way. Various stereoselective transformations of the adducts so formed are presented, using the total synthesis of brefeldin A—a typical natural product of this series—as example. Several methods for the synthesis of 4-oxo-2-cyclopentenyl acetate are outlined and, in addition, the more important methods for the enantioselective synthesis of other 4-substituted 2-cyclopenten-1-ones are discussed.