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The practice of deploying and teaching retrosynthesis is on the cusp of considerable change, which in turn forces practitioners and educators to contemplate whether this impending change will advance or erode the efficiency and elegance of organic synthesis in the future. A short treatise is presented herein that covers the concept of retrosynthesis, along with exemplified methods and theories, and an attempt to comprehend the impact of artificial intelligence in an era when freely and commercially available retrosynthetic and forward synthesis planning programs are increasingly prevalent. Will the computer ever compete with human retrosynthetic design and the art of organic synthesis? Will the computer ever compete with human retrosynthetic design and the art of organic synthesis? [ABSTRACT FROM AUTHOR]

The bulky, but symmetrically beautiful, adamantane ring system is now pervasive throughout physical, medicinal and synthetic chemistry, since it was first discovered in 1924 and coined 'dekaterpene'. This fascinating name lived up to its natural product roots when adamantane was isolated from crude oil in 1933, but it was not until 1957 in a landmark contribution by Paul von Ragué Schleyer that adamantane was made readily accessible through synthesis. Beyond the legacy to physical and medicinal chemistry, the adamantane moiety has been quintessential in the development of some of the most important catalysts to date. Considering adamantane's impact on catalyst development past, present and future, this subject is for the first time reviewed herein. [ABSTRACT FROM AUTHOR]

Numerous variations on structural motifs exist within pharmaceutical compounds that have entered the clinic. These variations have amounted over many decades based on years of drug development associated with screening natural products and de novo synthetic systems. Caged (or bridged) bicyclic structural elements offer a variety of diverse features, encompassing three-dimensional shape, and assorted pharmacokinetic properties. This review highlights approximately 20 all carbon cage containing pharmaceuticals, ranging in structure from bicyclo[2.2.1] through to adamantane, including some in the top-selling pharmaceutical bracket. Although, a wide variety of human diseases, illnesses and conditions are treated with drugs containing the bicyclic motif, a common feature is that many of these lipophilic systems display CNS and/or neurological activity. In addition, to an extensive overview of the history and biology associated with each drug, a survey of synthetic methods used to construct these entities is presented. An analysis section compares natural products to synthetics in drug discovery, and entertains the classical caged hydrocarbon systems potentially missing from the clinic. Lastly, this unprecedented review is highly pertinent at a time when big pharma is desperately trying to escape flatland drugs. [ABSTRACT FROM AUTHOR]

Bredt's rule holds a special place in the realm of physical organic chemistry, but its application to natural products chemistry-the field in which the rule was originally formulated-is not well defined. Herein, the use of olefin strain (OS) energy as a readily calculated predictor of the stability of natural products containing a bridgehead alkene is introduced. Schleyer first used OS energies to classify parent bridgehead alkenes into 'isolable', 'observable', and 'unstable' classes. OS calculations on natural products, using contemporary forcefield methods, unequivocally predict all structurally verified bridgehead alkene natural products to be 'isolable'. Thus, when one assigns the structure of a putative bridgehead alkene natural product, an OS in the 'observable' or 'unstable' ranges is a red flag for error. [ABSTRACT FROM AUTHOR]

Bredt's rule holds a special place in the realm of physical organic chemistry, but its application to natural products chemistry-the field in which the rule was originally formulated-is not well defined. Herein, the use of olefin strain (OS) energy as a readily calculated predictor of the stability of natural products containing a bridgehead alkene is introduced. Schleyer first used OS energies to classify parent bridgehead alkenes into 'isolable', 'observable', and 'unstable' classes. OS calculations on natural products, using contemporary forcefield methods, unequivocally predict all structurally verified bridgehead alkene natural products to be 'isolable'. Thus, when one assigns the structure of a putative bridgehead alkene natural product, an OS in the 'observable' or 'unstable' ranges is a red flag for error. [ABSTRACT FROM AUTHOR]

The article offers information on the 7th Heron Island Conference on Reactive Intermediates and Unusual Molecules – Synthesis and Mechanism held from July 9-15, 2016 at the Heron Island Resort on the Great Barrier Reef. Topics discussed include the chemistry topics discussed at the conference including physical, spectroscopic and mechanistic chemistry, Professors John Gladysz and Paul Chirik from "Organometallics" who attended the meeting, and several papers discussed at the conference.

Substituted phenanthridines, such as the natural product trispheridine, have been accessed by the practical photochemical cyclization of N-benzylanilines. Functionalities, with a focus on fluoro substituents and protected catechols, are well tolerated on both the A and C rings. The phenanthridines were accessed in good to very good yields (up to 95 %) from iodinated substrates, whereas brominated substrates performed poorly in comparison (0-48 %). [ABSTRACT FROM AUTHOR]

Alkynylsilver cations, RC≡CAg2+ (where R = Me and Ph) have been prepared in the gas phase using multistage mass spectrometry experiments in a quadrupole ion trap mass spectrometer. Two methods were used: (i) electrospray ionisation (ESI) of a mixture of AgNO3 (in MeOH/H2O/acetic acid) and the alkyne carboxylic acid to yield the appropriate silver acetylide cations RC≡CAg2+, via a facile decarboxylation of the RC≡CCO2Ag2+ precursor; (ii) ESI of silver acetylides, RC≡CAg, which yields a cluster of the type, [(RC≡CAg)12Ag2Cl]+. Regardless of the method of preparation, these alkynylsilver cations, RC≡CAg2+, undergo ion-molecule reactions with allyliodide to yield the ionic products Ag2I+ and [(RC≡CCH2CH=CH2)Ag]+. The CID spectrum of [(PhC≡CCH2CH=CH2)Ag]+ was compared to that of an authentic sample of the silver adduct of 5-phenyl-1-penten-4-yne. Both ions fragment to yield Ag+ and the radical cation, PhC≡CCH2CH=CH2+Ṗ, confirming that C–C bond coupling has taken place in the gas phase. DFT calculations were carried out on these C–C bond coupling reactions for the system R = Me. The reaction is highly exothermic and involves the initial coordination of the allyliodide to both silver atoms, with the iodine coordinating to one atom and the alkene moiety coordinating to the other. The overall mechanism of C–C bond coupling involves oxidative addition of the allyliodide followed by reductive elimination of RC≡CCH2CH=CH2, to ultimately yield two sets of reaction products: (i) Ag2I+ and RC≡CCH2CH=CH2; and (ii) [(RC≡CCH2CH=CH2)Ag]+ and AgI. [ABSTRACT FROM AUTHOR]

A 2-azabicyclo[4.2.0]octa-4,7-diene derivative was unexpectedly isolated from the photochemical irradiation of 2-vinyl-1,2-dihydropyridine. A cascading 6π–8π–4π electrocyclic rearrangement has been proposed as a possible mechanistic pathway. Herein disclosed is the isolation of the 2-azabicyclo[4.2.0]octa-4,7-diene skeleton derived from the photochemical irradiation of 2-vinyl-1,2-dihydropyridine. A cascading 6π–8π–4π electrocyclic rearrangement is proposed as the mechanistic rationale. This is the first observation of this ring system. [ABSTRACT FROM AUTHOR]

A review surveying the synthetic methodology developed by the Williams group over the last ten years, driven by natural product total synthesis, is presented. An underlying theme over this time has been the reliance on physical organic chemistry, organometallics and the cyclohexane ring system. [ABSTRACT FROM AUTHOR]

An improved photochemical method for producing the prolifically bioactive phenanthridine system is reported. A wide variety of derivatives were obtained in two steps in yields ranging from 31 to 95%. [ABSTRACT FROM AUTHOR]

Abstract: A one pot synthesis of the 3,3-dimethylacroyl enol ester function found in the vibsane type diterpenes has been developed based on the Anders–Gaßner variant of the Wittig reaction (AGW reaction). This method uses easily accessible acyloxyalkylidene phosphoranes and a variety of aldehydes. [Copyright &y& Elsevier]

Abstract: Azedaralide, a potentially advanced intermediate for the total synthesis of various tetranortriterpenes, was constructed utilising the Fernández-Mateos protocol and assigned both relative and absolute stereochemistries. Both asymmetric aldol and classical chiral resolution attempts failed to deliver pure enantiomers whereas preparative chiral chromatography resolved racemic azedaralide with ease. [Copyright &y& Elsevier]

Abstract: Specific 3-azabicyclo[3.3.1]nonane derivatives undergo skeletal cleavage when subjected to light or Lewis acidic conditions affording novel heterotricycles, which is in stark contrast to 3-oxabicyclo[3.3.1]nonanes. [Copyright &y& Elsevier]

Abstract: Rapid access to the ABCE ring system of the C-20 diterpene alkaloids was achieved by silver (I) promoted intramolecular Friedel–Crafts arylation of a functional group specific 5-bromo-3-azabicyclo[3.3.1]nonane derivative. [Copyright &y& Elsevier]

The bicyclo[3.3.1]non-1-en-3-one motif, which has yet to be observed in natural products, was recently reported within the skeleton of neoveratrenone. On the basis of Bredt's rule, a plausible reassignment matching closely the C-nor-D-homo steroidal ring system has been proposed herein. [ABSTRACT FROM AUTHOR]

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g. a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9‐azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9‐azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1‐azahomocubane. [ABSTRACT FROM AUTHOR]

The tetranortriterpene cipadonoid B was efficiently constructed from synthetic azedaralide in a one-pot cascade, viathe underutilised ketal-Claisen rearrangement. [ABSTRACT FROM AUTHOR]

Abstract: 3-Hydroxy-5-oxo esters are useful precursors to biologically active compounds. An expedient three-step synthesis of 3-hydroxy-5-oxo esters based on dithiane anion chemistry is presented along with the transformation of the 3-hydroxy-5-oxo esters into 5,6-dihydropyran-2-ones. [Copyright &y& Elsevier]

A one-step method for the conversion of isopropyl protected guaiacols to the corresponding acetates is reported. Treating 6-substituted isopropyl protected guaiacols with trimethylsilyl trifluoromethanesulfonate in a mixture of acetic anhydride and acetonitrile affords 6-substituted guaiacol acetates in yields ranging from 35% to 99%. [Copyright &y& Elsevier]

Using computational methods and chemical intuition, the proposed structure of janthinolide A is shown to be incorrect. It is further shown that the material described as janthinolide A is highly likely to be janthinolide C. [ABSTRACT FROM AUTHOR]

With the burgeoning interest in cage motifs for bioactive molecule discovery, and the recent disclosure of 1,4‐cubane‐dicarboxylic acid impact sensitivity, more research into the safety profiles of cage scaffolds is required. Therefore, the impact sensitivity and thermal decomposition behavior of judiciously selected starting materials and synthetic intermediates of cubane, bicyclo[1.1.1]pentane (BCP), and bicyclo[2.2.2]octane (BCO) were evaluated via hammer test and sealed cell differential scanning calorimetry, respectively. Iodo‐substituted systems were found to be more impact sensitive, whereas hydroxymethyl substitution led to more rapid thermodecomposition. Cubane was more likely to be impact sensitive with these substituents, followed by BCP, whereas all BCOs were unresponsive. The majority of derivatives were placed substantially above Yoshida thresholds—a computational indicator of sensitivity. [ABSTRACT FROM AUTHOR]

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that develops as a consequence of prolonged hyperglycaemia‐induced injury to the long nerves. Apart from pain, PDN is also characterized by morphine hyposensitivity. Intriguingly, in streptozotocin (STZ)‐induced diabetic rats exhibiting marked morphine hyposensitivity, dietary administration of the nitric oxide (NO) precursor, L‐arginine at 1 g/d, progressively rescued morphine efficacy and potency over an 8‐week treatment period. In earlier work, single bolus doses of the furoxan nitric oxide (NO) donor, PRG150 (3‐methylfuroxan‐4‐carbaldehyde), evoked dose‐dependent pain relief in STZ‐diabetic rats but the efficacious doses were 3‐4 orders of magnitude higher in advanced diabetes than that required in early STZ diabetes. Together, these findings suggested a role for NO in the modulation of μ‐opioid (MOP) receptor signalling. Therefore, the present study was designed to assess a role for NO released from PRG150, in modulating MOP receptor function in vitro. Here, we show an absolute requirement for the MOP receptor, but not the δ‐opioid (DOP) or the κ‐opioid (KOP) receptor, to transduce the cellular effects of PRG150 on forskolin‐stimulated cAMP responses in vitro. PRG150 did not interact with the classical naloxone‐sensitive binding site of the MOP receptor, and its effects on cAMP responses in HEK‐MOP cells were also naloxone‐insensitive. Nevertheless, the inhibitory effects of PRG150 on forskolin‐stimulated cAMP responses in HEK‐MOP cells were dependent upon pertussis toxin (PTX)‐sensitive Gi/o proteins as well as membrane lipid rafts and src kinase. Together, our findings implicate a role for NO in modulating MOP receptor function in vivo. [ABSTRACT FROM AUTHOR]

Structural misassignments of natural products are prevalent in the literature. Developing methods and theoretical concepts to assist those undertaking structural elucidation is therefore of paramount importance, such that biologists and synthetic chemists avoid pursuing phantom chemical entities. Herein described is a strategy for predicting the isolabilities of oxygen‐substituted bridgehead natural products based on calculations of olefin strain energies, NMR chemical shifts and coupling constants (DU8+). This approach provides corroborating evidence for the structures of certain bridgehead alkene natural products while leading to the reassignment of several other structures. [ABSTRACT FROM AUTHOR]

Structural misassignments of natural products are prevalent in the literature. Developing methods and theoretical concepts to assist those undertaking structural elucidation is therefore of paramount importance, such that biologists and synthetic chemists avoid pursuing phantom chemical entities. Herein described is a strategy for predicting the isolabilities of oxygen‐substituted bridgehead natural products based on calculations of olefin strain energies, NMR chemical shifts and coupling constants (DU8+). This approach provides corroborating evidence for the structures of certain bridgehead alkene natural products while leading to the reassignment of several other structures. [ABSTRACT FROM AUTHOR]

Review: [143 refs. [ABSTRACT FROM AUTHOR]

Review: [117 refs. [ABSTRACT FROM AUTHOR]

The front cover image, provided by Kylie Agnew ‐ Francis and Craig Williams, illustrates diverse examples of catalytic systems that contain the sterically bulky adamantane moiety. This ‘big guy’ molecule has become well regarded in the literature for its powerful electron ‐ donating properties in addition to its size, and has thus marked its place in the organic chemist’s toolbox as an excellent (and often superior) addition to catalyst and ligand design. Details can be found in the review on pages 675 – 700 (K. A. Agnew ‐ Francis, C. M. Williams, Adv. Synth. Catal.­ 2016, 358, 675 – 700; DOI:10.1002/adsc.201500949). [ABSTRACT FROM AUTHOR]

Review: 376 refs. [ABSTRACT FROM AUTHOR]

Bredt's rule for bridgehead alkenes is important for physical organic chemists, but has been rarely applied to natural products. In their Communication on page 10608 ff., C. M. Williams and E. H. Krenske show that calculations of the olefin strain energy, first introduced by Schleyer, predict the stability of complex natural products containing bridgehead alkenes. This method can be used to determine the viability of the structures of newly identified natural products proposed to contain a bridgehead alkene. [ABSTRACT FROM AUTHOR]

Die Bredt ‐ Regel für Brückenkopfalkene ist für physikalisch ‐ organische Chemiker von großem Interesse, wurde jedoch selten auf Naturstoffe angewendet. In der Zuschrift auf S. 10754 ff. zeigen C. M. Williams und E.H. Krenske, wie Berechnungen der Olefinspannungsenergie, eingeführt von Schleyer, die Stabilität komplexer Naturstoffe mit Brückenkopfalkenen vorhersagen. Dies hilft, die Plausibilität der Struktur neu identifizierter Naturstoffe, bei denen eine Brückenkopfalkeneinheit vermutet wird, zu prüfen. [ABSTRACT FROM AUTHOR]

Chemical reactions related to the article "The anti-Bredt Red Flag! Reassignment of Neoveratrenone (I)" by A. I. Savchenko and others are presented.

A practical, convenient, and rapid access to phenanthridine derivatives by photochemical cyclization of iodo- or bromo-substituted benzylanilines is reported. [ABSTRACT FROM AUTHOR]

The redox and ligand exchange reactions of oxido-ruthenium complexes are central to the function of the Sharpless and Griffith–Ley one-step alcohol oxidation protocols. However, their mechanisms have not been elucidated. Cyclic voltammetry and UV-vis spectroelectrochemical analysis of [RuO4]− has provided new insight into the key ruthenium oxidation states involved in catalysis. Furthermore, the oxidation states sensitive to the presence of the N-oxide co-oxidant N-methylmorpholine N-oxide (NMO), and its role in catalysis, have been determined. [ABSTRACT FROM AUTHOR]

The article offers information on the changes related to the International Collaborative and Cooperative Chemistry Symposium (ICCCS). It is mentioned that the 2nd ICCCS was held at the University of Queensland in Queensland from October 30 to November 2, 2011. Also, the relationship between the chemistry department of the Queensland university with the Asian counterparts was started in 2007 and professor Andy Hor played a major role in forming the partnership.

Review: 23 refs. [ABSTRACT FROM AUTHOR]

Review: 31 refs. [ABSTRACT FROM AUTHOR]

Natural products continue to be reported at an astonishing rate from a wide range of multidisciplinary research activities in the pursuit of understanding the chemistry of biodiversity. However, the elucidation of chemical structure in the modern era is heavily reliant on the analysis and interpretation of multiple spectroscopic outputs, and in most cases this activity is by no means trivial. Structural errors continue to be described given the inherent complexity of natural products. Computer‐Assisted Structure Elucidation (CASE) continues to provide improved resolving power in this regard, but for enhanced accuracy quantum chemical spectrum prediction methodology is paramount. Reported herein are a range of counterfactual natural products, identified through chemical principal screening, which have been reassigned using a combination of chemical intuition, chemical synthesis, CASE and DU8+ spectrum prediction. [ABSTRACT FROM AUTHOR]

Acetohydroxyacid synthase (AHAS) inhibitors are highly successful commercial herbicides. New kinetic data show that the binding of these compounds leads to reversible accumulative inhibition of AHAS. Crystallographic data (to a resolution of 2.17 Å) for an AHAS-herbicide complex shows that closure of the active site occurs when the herbicidal inhibitor binds, thus preventing exchange with solvent. This feature combined with new kinetic data shows that molecular oxygen promotes an accumulative inhibition leading to the conclusion that the exceptional potency of these herbicides is augmented by subversion of an inherent oxygenase side reaction. The reactive oxygen species produced by this reaction are trapped in the active site, triggering oxidation reactions that ultimately lead to the alteration of the redox state of the cofactor flavin adenine dinucleotide (FAD), a feature that accounts for the observed reversible accumulative inhibition. [ABSTRACT FROM AUTHOR]

Acetohydroxyacid synthase (AHAS) inhibitors are highly successful commercial herbicides. New kinetic data show that the binding of these compounds leads to reversible accumulative inhibition of AHAS. Crystallographic data (to a resolution of 2.17 Å) for an AHAS-herbicide complex shows that closure of the active site occurs when the herbicidal inhibitor binds, thus preventing exchange with solvent. This feature combined with new kinetic data shows that molecular oxygen promotes an accumulative inhibition leading to the conclusion that the exceptional potency of these herbicides is augmented by subversion of an inherent oxygenase side reaction. The reactive oxygen species produced by this reaction are trapped in the active site, triggering oxidation reactions that ultimately lead to the alteration of the redox state of the cofactor flavin adenine dinucleotide (FAD), a feature that accounts for the observed reversible accumulative inhibition. [ABSTRACT FROM AUTHOR]

Painful diabetic neuropathy ( PDN) is a type of peripheral neuropathic pain that is often intractable. Elevated nitric oxide ( NO) from neuronal and non-neuronal sources in the somatosensory system is implicated in the pathobiology of peripheral neuropathic pain. However, in diabetes, nitrergic nerve degeneration to deplete NO bioactivity appears causal in the pathogenesis of irreversible autonomic neuropathy, another long term complication of diabetes. Hence, this study hypothesized that progressive NO depletion may underpin the pathobiology of PDN and that NO donors may alleviate PDN. Diabetes was induced in rats with intravenous streptozotocin ( STZ) at 70 mg/kg and confirmed if blood glucose levels ( BGLs) on day 10 post- STZ were ≥15 mmol/L. Analgesic efficacy of subcutaneous (s.c.) bolus doses of the furoxan NO donor, PRG150 was assessed in the STZ-diabetic rat model of PDN at 10-, 14- and 24-weeks post- STZ relative to the sydnominine NO donor, SIN-1 and its prodrug, molsidomine. PRG150 produced dose-dependent analgesia in STZ-diabetic rats whereas SIN-1 and molsidomine evoked neuro-excitatory side-effects, but not analgesia. The 1000-fold larger doses of PRG150 needed to produce analgesia at 14- and 24-weeks (800 pmol/kg) c.f. 10-weeks (8 fmol/kg) post- STZ in rats, suggest that progressive NO depletion is also causal in PDN. Importantly, doses of PRG150 up to 10 000 fold higher than the analgesic dose did not produce hypotension in rats. The 50-fold greater release of NO by SIN-1 c.f. PRG150 in vitro, may underpin the neuro-excitatory rather than analgesic effects of SIN-1/molsidomine. PRG150 is worthy of further investigation as a potential novel analgesic for PDN. [ABSTRACT FROM AUTHOR]

N,N,N′,N′-Tetramethylethylenediamine dioxide (TMEDAO2) was explored as a more atom economical co-oxidant for the Ley–Griffith oxidation of alcohols to aldehydes. TMEDAO2 was found to selectivity oxidise benzylic and allylic alcohols in comparable yields to that of the standard Ley–Griffith co-oxidant (NMO). Importantly TMEDAO2 facilitated tandem Ley–Griffith-Wittig reactions with stabilised ylides, in good to excellent yields, without the requirement of anhydrous conditions. [ABSTRACT FROM AUTHOR]

Unusual polyenols that defied chemical principles were reassigned as the nucleosides, adenosine and uridine, using a combination of chemical intuition underpinned by Computer Assisted Structure Elucidation (CASE) and DFT methods. [ABSTRACT FROM AUTHOR]

UbiA prenyltransferase domain‐containing protein‐1 (UBIAD1) is responsible for the biosynthesis of menaquinone‐4 (MK‐4), a cofactor for extrahepatic carboxylation of vitamin K‐dependent (VKD) proteins. Genetic variations of UBIAD1 are mainly associated with Schnyder corneal dystrophy (SCD), a disease characterized by abnormal accumulation of cholesterol in the cornea. Results from in vitro studies demonstrate that SCD‐associated UBIAD1 mutations are defective in MK‐4 biosynthesis. However, SCD patients do not exhibit typical phenotypes associated with defects of MK‐4 or VKD carboxylation. Here, we coupled UBIAD1's biosynthetic activity of MK‐4 with VKD carboxylation in HEK293 cells that stably express a chimeric VKD reporter protein. The endogenous Ubiad1 gene in these cells was knocked out by CRISPR‐Cas9‐mediated genome editing. The effect of UBIAD1 mutations on MK‐4 biosynthesis and VKD carboxylation was evaluated in Ubiad1‐deficient reporter cells by determining the production of MK‐4 or by measuring the efficiency of reporter‐protein carboxylation. Our results show that the hot‐spot mutation N102S has a moderate impact on MK‐4 biosynthesis (retained ˜ 82% activity) but does not affect VKD carboxylation. However, the G186R mutation significantly affected both MK‐4 biosynthesis and VKD carboxylation. Other mutations exhibit varying degrees of effects on MK‐4 biosynthesis and VKD carboxylation. These results are consistent with in vivo results obtained from gene knock‐in mice and SCD patients. Our findings suggest that UBIAD1's MK‐4 biosynthetic activity does not directly correlate with the phenotypes of SCD patients. The established cell‐based assays in this study provide a powerful tool for the functional studies of UBIAD1 in a cellular milieu. [ABSTRACT FROM AUTHOR]

A non-hygroscopic tetraphenylborate salt of N-methylmorpholine- N-oxide (NMO) is reported (NMO ⋅TPB), which modulates the standard Ley-Griffith oxidation such that benzylic and allylic alcohols are oxidised selectively. An attractive feature of this new protocol is that anhydrous conditions are not required for this selective tetra- n-propylammonium perruthenate (TPAP) oxidation, superseding the requirement of molecular sieves. [ABSTRACT FROM AUTHOR]

Well over a hundred years ago, Professor Julius Bredt embarked on a career pursuing and critiquing bridged bicyclic systems that contained ring strain induced by the presence of a bridgehead olefin. These endeavors founded what we now know as Bredt's rule (Bredtsche Regel). Physical, theoretical, and synthetic organic chemists have intensely studied this premise, pushing the boundaries of such systems to arrive at a better understood physical phenomenon. Mother nature has also seen fit to construct molecules containing bridgehead double bonds that encompass Bredt's rule. For the first time, this topic is reviewed in a natural product context. [ABSTRACT FROM AUTHOR]

Vor über hundert Jahren begann Professor Julius Bredt seine Forschungskarriere auf dem Gebiet der verbrückten bicyclischen Systeme, die durch ein Brückenkopf-Alken unter Ringspannung stehen. Seine kritischen Betrachtungen mündeten in der Formulierung dessen, was wir heute als die Bredtsche Regel kennen. Seitdem versuchen Physikochemiker, Theoretiker und Synthesechemiker gleichermaßen, die Grenzen dieses physikalische Phänomens auszuloten, um es besser kennenzulernen. Der Bauplan der Natur sieht durchaus Brückenkopf-Doppelbindungen nach der Bredtschen Regel vor. In diesem Aufsatz wird erstmals die Anwendung der Bredtschen Regel auf Naturstoffe umfassend erörtert. [ABSTRACT FROM AUTHOR]