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We describe two attempts to the synthesis of novel constrained L-AP4 analogs of potential antagonist activity. Although the first approach to introduce alkyl substituent on the amino acid carbon using cyclopropyl keton failed, conversion of cyclopropanecarboxylate into corresponding β-ketophosphonate is promising and more general. [ABSTRACT FROM AUTHOR]

Introduction: Etomidate is no longer administered as a continuous infusion for anesthetic maintenance or sedation, because it results in profound and persistent suppression of adrenocortical steroid synthesis with potentially lethal consequences in critically ill patients. We hypothesized that rapidly metabolized soft analogues of etomidate could be developed that do not produce persistent adrenocortical dysfunction even after prolonged continuous infusion. We hope that such agents might also provide more rapid and predictable anesthetic emergence. We have developed the soft etomidate analogue cyclopropyl-methoxycarbonyl etomidate (CPMM). Upon termination of 120-minute continuous infusions, hypnotic and encephalographic recoveries occur in four minutes. The aims of this study were to assess adrenocortical function during and following 120-minute continuous infusion of CPMM and to compare the results with those obtained using etomidate. Methods: Dexamethasone-suppressed rats were randomized into an etomidate group, CPMM group, or control group. Rats in the etomidate and CPMM groups received 120-minute continuous infusions of etomidate and CPMM, respectively. Rats in the control group received neither hypnotic. In the first study, adrenocortical function during hypnotic infusion was assessed by administering adrenocorticotropic hormone (ACTH) 90 minutes after the start of the hypnotic infusion and measuring plasma corticosterone concentrations at the end of the infusion 30 minutes later. In the second study, adrenocortical recovery following hypnotic infusion was assessed by administering ACTH every 30 minutes after infusion termination and measuring plasma corticosterone concentrations 30 minutes after each ACTH dose. Results: During hypnotic infusion, ACTH-stimulated serum corticosterone concentrations were significantly lower in the CPMM and etomidate groups than in the control group (100 ± 64 ng/ml and 33 ± 32 ng/ml versus 615 ± 265 ng/ml, respectively). After hypnotic infusion, ACTH-stimulated serum corticosterone concentrations recovered to control values within 30 minutes in the CPMM group but remained suppressed relative to those in the control group for more than 3 hours in the etomidate group. Conclusions: Both CPMM and etomidate suppress adrenocortical function during continuous infusion. However, recovery occurs significantly more rapidly following infusion of CPMM. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (−)-1b, (−)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. [Copyright &y& Elsevier]

Abstract: Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure–activity relationship (SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors. [Copyright &y& Elsevier]

Under a halo: Selective iron‐catalyzed hydrodehalogenations of dibromo‐ and dichlorocyclopropanes are effectively realized with tBuMgCl as the reductant. The reactions proceed under mild conditions and exhibit superior selectivities to iron‐free protocols, as no allenes are formed. The sequential combination of base‐mediated dihalocyclopropanation and this mono‐dehalogenation provides straightforward access to substituted monohalocyclopropanes. [ABSTRACT FROM AUTHOR]

Abstract: Novel 3′-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4-quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by 1H, 13C and 19F NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R8 and a secondary carbamate in R3′) and compound 5 (with a hydrogen in R8 and an ethyl ester in R3′) displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R3′ substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. [Copyright &y& Elsevier]

The title compound was synthesized mainly by palladium catalytic coupling, cyclopropyl ring-opening rearrangement, epoxidation, Swern oxidation, demethanol reactions, and selective reduction. This synthesis was achieved in 16 steps with 9.7% overall yield. Unfortunately, the published spectroscopic data do not match with those of our synthetic compound. [ABSTRACT FROM AUTHOR]

Abstract: Methylation of t-butyl-1-dimethylphosphono-2-p-tolylsulfinyl cyclopropanecarboxylic ester occurs with full inversion of the configuration, but the stereochemistry of carbanion formation is structure-dependent. Reaction of cyclopropyl sulfoxide with i-PrMgCl leads to unprecedented 1,2 migration of the phosphoryl group. [Copyright &y& Elsevier]

Abstract: Constrained L-AP4 analogues, (2S,1′R,2′S)- and (2S,1′S,2′R)-2-(2′-phosphonocyclopropyl) glycines as well as their phenyl analogues (2S,1′S,2′R,3′S)-2-(2′-phosphono-3′-phenylcyclopropyl) glycine (PPCG-1) and (2S,1′R,2′S,3′R)-2-(2′-phosphono-3′-phenylcyclopropyl) glycine (PPCG-2) were synthesized. The stereogenic centers in cyclopropane ring were formed under sulfinyl group control, in asymmetric cyclopropanation of enantiomerically pure α-phosphoryl vinyl sulfoxides. The sulfinimine-mediated asymmetric Strecker reaction allowed to introduce amino acid moiety. [Copyright &y& Elsevier]

1H and 13C NMR chemical shifts of iron porphyrin complexes are determined mainly by the spin densities at the peripheral carbon and nitrogen atoms caused by the interaction between paramagnetic iron 3d and porphyrin molecular orbitals. This review describes how the half-occupied iron 3d orbitals such as dπ(dxz, dyz), dxy, d [ABSTRACT FROM AUTHOR]

A new route to Roflumilast, a selective phosphodiesterase type 4 (PDE 4) inhibitor, is described. The synthetic procedure starts from 4-hydroxy-3-iodobenzoic acid to access the key intermediate 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid via copper-catalyzed hydroxylation and utilizes amide coupling to accomplish the synthesis of Roflumilast in 80% overall yield. [ABSTRACT FROM AUTHOR]

A new mechanism for the origin of multiple skeletal isomers observed in the cationic dimerization of 1-decene is proposed, and products that should form based on this mechanism are predicted. A protonated cyclopropyl intermediate appeared to form directly from combination of 2-decyl carbocation with 1-decene; formation of this intermediate did not appear to occur via ring closure of a branched secondary carbocation. The authors propose that rapid, repeated isomerizations of the protonated cyclopropyl intermediates lead to multiple skeletal isomers in decene dimers. The proposed mechanism can account for structures previously identified in mixtures of decene dimers and butene dimers. [ABSTRACT FROM AUTHOR]

Peripheral selective μ opioid receptor (MOR) antagonistscould alleviate the symptoms of opioid-induced constipation (OIC)without compromising the analgesic effect of opioids. However, a varietyof adverse effects were associated with them, partially due to theirrelatively low MOR selectivity. NAP, a 6β-N-4′-pyridyl substituted naltrexamine derivative, was identifiedpreviously as a potent and highly selective MOR antagonist mainlyacting within the peripheral nervous system. The noticeable diarrheaassociated with it prompted the design and synthesis of its analoguesin order to study its structure–activity relationship. Amongthem, compound 8showed improved pharmacological profilescompared to the original lead, acting mainly at peripheral while increasingthe intestinal motility in morphine-pelleted mice (ED50= 0.03 mg/kg). The slight decrease of the ED50comparedto the original lead was well compensated by the unobserved adverseeffect. Hence, this compound seems to be a more promising lead todevelop novel therapeutic agents toward OIC. [ABSTRACT FROM AUTHOR]

We have previously shown that cinnamoyl derivatives of14β-amino-17-cyclopropylmethyl-7,8-dihydronormorphinoneand 7α-aminomethyl-6,14-endoethanonororipavine have pronouncedpseudoirreversible μ opioid receptor (MOR) antagonism. The presentcommunication describes the synthesis and evaluation of fumaroylaminoanalogues of these cinnamoylamino derivatives together with some relatedfumaroyl derivatives. The predominant activity of the new ligandswas MOR antagonism. The fumaroylamino analogues (2a, 5a) of the pseudoirreversible antagonist cinnamoylamino morphinonesand oripavines (2b, 5b) were themselvesirreversible antagonists in vivo. However the fumaroylamino derivativeshad significantly higher MOR efficacy than the cinnamoylamino derivativesin mouse antinociceptive tests. Comparison of 2aand 5awith the prototypic fumaroylamino opioid β-FNA (1a) shows that they have similar MOR irreversible antagonistactions but differ in the nature of their opioid receptor agonisteffects; 2ais a predominant MOR agonist and 5ashows no opioid receptor selectivity, whereas the agonist effectof β-FNA is clearly κ opioid receptor (KOR) mediated. [ABSTRACT FROM AUTHOR]

The chemical shifts of the diastereotopic hydrogens ofthe ethylgroup of the cyclopropane ring-opening product of conjugate additionof LiCu(CH3)2to cyclopropyl enone 1were computed. Comparison of computed and observed 1HNMR chemical shifts of the diastereotopic hydrogens of the ethyl groupof 2established the stereochemistry of the ring-openingproduct as 2d-b. This provides evidencethat the reaction proceeds by conjugate addition of the cuprate tothe enone, followed by ring-opening of the cyclopropylmethyl copperspecies and reductive elimination. [ABSTRACT FROM AUTHOR]

(S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and methylenecyclopropyl-containing compounds were synthesized and studied as radical clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)-isomers of the cyclopropyl-containing analogues were efficiently converted to epoxide and ketone products by HppE, respectively. In contrast, the ultrafast methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid radical-triggered ring-opening process that leads to enzyme inactivation. Taken together, these findings provide, for the first time, experimental evidence for the involvement of a C2-centered radical intermediate with a lifetime on the order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP. [ABSTRACT FROM AUTHOR]

Cyclopropanes occur in a diverse array of natural products, including pheromones, steroids, terpenes, fatty acid metabolites, and amino acids, and compounds that contain cyclopropanes exhibit interesting and important pharmacological properties. These valuable synthetic intermediates can be functionalized, or their rings can be opened, and the synthetic utility and unique biological activity of cyclopropanes have inspired many investigations into their preparation. One of the most powerful methods to generate cyclopropanes is the Simmons–Smith cyclopropanation. Since the original studies in the late 1950s reported that IZnCH2I could transform alkenes into cyclopropanes, researchers have introduced various modifications of the original procedure. Significantly, Furukawa demonstrated that diethylzinc and CH2I2react to generate carbenoids, and Shi described more reactive zinc carbenoids that contain electron-withdrawing groups on zinc (XZnCHI2). Despite these advances, the development of catalytic asymmetric Simmons–Smith reactions remains challenging. Although researchers have achieved catalytic asymmetric cyclopropanation of allylic alcohols, these reactions have had limited success. One attractive approach to the synthesis of cyclopropanes involves tandem reactions, where researchers carry out sequential synthetic transformations without the isolation or purification of intermediates. Such a synthetic strategy minimizes difficulties in the handling and purification of reactive intermediates and maximizes yields and the generation of molecular complexity. [ABSTRACT FROM AUTHOR]

Abstract: Ab-initio and density functional theory calculations have been performed to investigate the ring-opening reactions of 1-bromo-1-lithiodisilirane (5), 3-bromo-3-lithiodisilirane (6), and 1-bromo-1-lithiotrisilirane (7) to 1,2-disilaallene (9), 1,3-disilaallene (10), and trisilaallene (11), respectively. Formally, the ring-opening mechanism of silacyclopropylidenoids may be either concerted or stepwise involving the intermediacy of a free silacyclopropylidene or cyclopropylidene. The ring-opening of 5 to 9 can proceed in both concerted and stepwise mechanism, where high activation energy barriers need to be overcome in order to open the silacyclopropylidene ring and to generate 9. In contrast, the ring-opening reactions of 6 and 7 can occur in a concerted fashion. The activation energy barrier for the isomerization of 6 to the complex of 10 with LiBr was determined to be only 2.3 kcal/mol at the B3LYP/6-31G(d) level, and the reaction is highly exothermic, by 37.0 kcal/mol, which makes this reaction for a promising strategy for the synthesis of 1,3-disilaallenes. However, the barrier for the conversion of 7 to 11 is calculated to be quite high, 27.5 kcal/mol, and in this case the reaction is endothermic, by 8.8 kcal/mol. [Copyright &y& Elsevier]

Valley-ridge inflection points (VRI) on the potential energy surface for the ring opening of the cyclopropyl radical to the allyl radical are determined using the tool of Newton trajectories (NTs) (Quapp and Schmidt in Theor Chem Acc 128:47, ). The UHF surface is treated in a former paper (Quapp et al. in Theor Chem Acc 129:803, ). This paper is the extension to the more expensive CASSCF(3,3) surface. We compare the results on the UHF surface with the more appropriate calculation: there are quantitative as well as qualitative changes, of course. But many fundamental relations are the same on both surfaces. However, we could detect new pathways on the CASSCF(3,3) surface which highlight the bifurcation problem of this radical. VRIs play a role in the understanding of bifurcating reactions. The region where the bifurcation takes place is governed by a VRI point. Because the transition state of the ring opening is not symmetric, the steepest descent (SD) from the transition state is not along a symmetry axis either, and in this case the SD usually fails a downhill VRI point. The SD from the transition state of the ring opening goes to the disrotatory minimum of the allyl radical. In contrast, we find some pathways which end at the conrotatory minimum, and which go along so-called non steepest descent paths, at least in parts. The region of interest (around the SP of the ring opening) is crossed by electronic intersection seams. Conical intersection points on the seam can be detected by NTs. We use the possibility to explore parts of the intersection seam of the lower CAS surface and we determine connected VRI points being the corner stones of the possible ring opening channels in the disrotatory and the conrotatory case. [ABSTRACT FROM AUTHOR]

Abstract: Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are the current focus on the indication for the management of hyperglycemia in diabetes. Here, a novel series of C-linked indolylxyloside-based inhibitors of SGLT2 has been discovered. Structure–activity relationship studies revealed that substituents at the 7-position of the indole moiety and a p-cyclopropylphenyl group in the distal position were necessary for optimum inhibitory activity. The pharmacokinetic study demonstrates that the most potent compound 1i is metabolically stable with a low clearance in rats. In further efficacy study, 1i is found to significantly lower blood glucose levels of streptozotocin (STZ)-induced diabetic rats. [Copyright &y& Elsevier]

We have developed two different types of tandem reactions for the synthesis of highly functionalized cyclohexenones from cyclopropyl substituted propargyl esters. Both reactions were initiated by rhodium-catalyzed Saucy--Marbet 1,3-acyloxy migration. The resulting cyclopropyl substituted allenes derived from acyloxy migration then underwent [5 + 1] cycloaddition with CO. The acyloxy group not only eased the access to allene intermediates but also provided a handle for further selective functionalizations. [ABSTRACT FROM AUTHOR]

In this work, we present a deep theoretical study on the intriguing and unexpected gold-catalyzed cycloisomerization of siloxy enynes to cyclohexadienes. To this end, we have evaluated the electronic and steric properties for three types of alkynyl substituents along the reaction paths and the implications on the evolution through divergent, competitive pathways. For an alkynyl -OR substituent, the results strongly suggest a polarization of the π electrons along the delocalized C2-C1-O system in the key cyclopropyl-carbene intermediate, which is enhanced by the bulkiness of the R group. The results reproduce the experimental observations in excellent agreement and provide interesting and useful clues for predicting the effects of the alkynyl substituent on the nature of the key intermediate and, hence, on the reactivity mode and selectivity. [ABSTRACT FROM AUTHOR]

Abstract: Methods for the synthesis of cyclopropyl glycosides and their use as glycosyl donors are described. Cyclopropyl glycosides containing different substituents were prepared by cyclopropanation of the corresponding vinyl glycosides, or by glycosidation of cyclopropyl alcohols that are synthesized by the Kulinkovich reaction. 1-Methyl- and 1-phenyl-substituted cyclopropyl glycosides undergo coupling to Fmoc-protected serine and threonine and to partially protected monosaccharides in the presence of TMS triflate to give glycosidated products. [Copyright &y& Elsevier]

Abstract: Recently, valley–ridge inflection points on the potential energy surface for the ring opening of the cyclopropyl radical have been determined using Newton trajectories (NTs) [W. Quapp, J.M. Bofill, A. Aguilar-Mogas, Theor. Chem. Acc. 129 (2011) 803]. This Letter is the report about the utilization of NTs for the search for conical intersection (CI) points. These points play a main role in the understanding of intersections of different electronic surfaces which open the door for photochemical reactions. We explain the reason why Newton trajectories can find CI points, and report a CI seam on the CASSCF (3,3) surface of the allyl radical ring closure. [Copyright &y& Elsevier]

Edessa meditabunda is a secondary pest within the piercing-sucking stink bug complex that attacks soybean crops in Brazil . The behavioral responses of males and females to aeration extracts from conspecifics suggested the presence of a male-produced sex pheromone. Gas chromatographic (GC) analysis of male and female aeration extracts revealed the presence of two male-specific compounds in a ratio of 92:8. Gas chromatographic -electroantennographic detection (GC-EAD) assays indicated that the major component is bioactive for females, supporting the behavioral data. Analysis of the mass and infrared spectra of the male-specific compounds suggested that they were both methyl-branched long-chain methyl esters. On the basis of the mass spectra of the respective hydrocarbons obtained by micro derivatizations, the structures of these methyl esters were proposed to be methyl 4,8,12-trimethylpentadecanoate (major) and methyl 4,8,12-trimethyltetradecanoate (minor). An 11 step synthetic route that was based on a sequence of Grignard reactions, starting from cyclopropyl methyl ketone, was developed to obtain synthetic standards with a 7.9 % overall yield for the major compound and a 9.9 % yield for the minor. The synthetic standards co-eluted with the natural pheromones on three different GC stationary phases. Y-tube olfactometer assays showed that the synthetic standards, including the major compound alone and a mixture of the major and minor compounds in the proportion found in natural extracts, were strongly attractive to females. [ABSTRACT FROM AUTHOR]

Treatment of 1-chlorocyclopropyl p-tolyl sulfoxides and 1-chlorocyclobutyl p-tolyl sulfoxides with a Grignard reagent at low temperature afforded cyclopropylmagnesium carbenoids and cyclobutylmagnesium carbenoids, respectively, via a sulfoxide- magnesium exchange reaction. The reaction of these magnesium carbenoids with lithium phenolates afforded spiro[2.6]nona-6,8- dien-5-ones and spiro[3.6]deca-7,9-dien-6-ones, respectively; however, the yields were rather low. Reaction of the cyclopropylmagnesium carbenoids with lithium 1-naphtholates gave spiro[2.6]nona- 5,7-dien-4-ones in moderate to good yields; however, reaction of the cyclobutylmagnesium carbenoids with lithium 1-naphtholates did not give the desired products. Reaction of the cyclopropyl- and cyclobutylmagnesium carbenoids with lithium 2-naphtholates gave spiro[2.6]nona-5,7-dien-4-ones and spiro[3.6]deca-7,9-dien-6- ones, respectively, in moderate to good yields. These unprecedented reactions provide a procedure for the synthesis of spiro[2.6]nona- 5,7-dien-4-ones and spiro[3.6]deca-7,9-dien-6-ones from 1-naphthols and 2-naphthols with a one-carbon ring expansion of the phenol ring. [ABSTRACT FROM AUTHOR]

Air oxidation of N-cyclopropylanilines was shown to occur under either ambient conditions or accelerated conditions (warming or shining light) in an open container. A subsequent fragmentation resulted in formation of the corresponding acetamide. While potential mechanisms have been previously proposed, simple aerobic oxidation to β-hydroxy-propionamides in the absence of a radical promoter has not been previously reported. [ABSTRACT FROM PUBLISHER]

Abstract: A novel, potent and selective quinazolinone series of inhibitors of p38α MAP kinase has been identified. Modifications designed to address the issues of poor aqueous solubility and high plasma protein binding as well as embedded aniline functionalities resulted in the identification of a clinical candidate N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703). Optimisation was guided by understanding of the binding modes from X-ray crystallographic studies which showed a switch from DFG ‘out’ to DFG ‘in’ as the inhibitor size was reduced to improve overall properties. [Copyright &y& Elsevier]

Abstract: The scope and limitations of a novel intramolecular azetidine ring-opening/closing cascade reaction affording spirocyclopropyl γ-lactams from azetidines in high regio- and stereoselectivity is reported. The key step of the process is a SN2-type ring-opening of TMSOTf-activated azetidine rings by silyl ketene acetals generated by treatment with TMSOTf and TEA. This study is a very rare example of nucleophilic ring-opening of azetidines that does not require formation of quaternary azetidinium salts by N-alkylation or the use of N-electron-withdrawing groups. Application of this process to 2-azetidinone system led to a complete change in reactivity and provide 6-aza-bicyclo[3.2.0]heptane derivatives via an unprecedented Mukaiyama aldol-like reaction involving an ester acceptor and a silyl imidate. [Copyright &y& Elsevier]

Copper(II)-mediated N-cyclopropylation of pyridinols involving copper(II) acetate, pyridine, and NaHMDS under microwave conditions in a dry air atmosphere is described. [ABSTRACT FROM AUTHOR]

The kinetics and equilibrium of the allyl radical reactionwithmolecular oxygen have been studied in direct measurements using temperature-controlledtubular flow reactor coupled to a laser photolysis/photoionizationmass spectrometer. In low-temperature experiments (T= 201–298 K), association kinetics were observed, and themeasured time-resolved C3H5radical signalsdecayed exponentially to the signal background. In this range, thedetermined rate coefficients exhibited a negative temperature dependenceand were observed to depend on the carrier-gas (He) pressure {p= 0.4–36 Torr, [He] = (1.7–118.0) ×1016cm–3}. The bimolecular rate coefficientsobtained vary in the range (0.88–11.6) × 10–13cm3s–1. In higher-temperature experiments(T= 320–420 K), the C3H5radical signal did not decay to the signal background, indicatingequilibration of the reaction. By measuring the radical decay rateunder these conditions as a function of temperature and followingtypical second- and third-law procedures, plotting the resulting ln Kpvalues versus 1/Tin a modifiedvan’t Hoff plot, the thermochemical parameters of the reactionwere extracted. The second-law treatment resulted in values of ΔH298°= −78.3 ± 1.1 kJ mol–1and ΔS298°= −129.9 ± 3.1 J mol–1K–1, with the uncertainties given as one standard error. When resultsfrom a previous investigation were taken into account and the third-lawmethod was applied, the reaction enthalpy was determined as ΔH298°= −75.6 ± 2.3 kJ mol–1. [ABSTRACT FROM AUTHOR]

Although they are highly strained, methylenecyclopropanes (MCPs) are readily accessible molecules that have served as useful building blocks in organic synthesis. MCPs can undergo a variety of ring-opening reactions because the release of cyclopropyl ring strain (40 kcal/mol) can provide a thermodynamic driving force for reactions and the π-character of the bonds within the cyclopropane can afford the kinetic opportunity to initiate the ring-opening. Since the 1970s, the chemistry of MCPs has been widely explored in the presence of transition metal catalysts, but less attention had been paid to the Lewis or Brønsted acid mediated chemistry of MCPs. During the past decade, significant developments have also been made in the Lewis or Brønsted acid mediated reactions of MCPs. This Account describes chemistry developed in our laboratory and by other researchers. [ABSTRACT FROM AUTHOR]

A highly diastereoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides with azoles is described. A wide range of azoles, including pyrroles, indoles, benzimidazoles, pyrazoles, and benzotriazoles, can be efficiently employed as pronucleophiles in this transformation, providing expeditious access to N-cyclopropyl heterocycles. [ABSTRACT FROM AUTHOR]

Efficient Csp³-Csp³ Suzuki couplings have been developed with both potassium cyclopropyl- and alkoxymethyltrifluoroborates. Moderate to good yields have been achieved in the cross-coupling of potassium cyclopropyltrifluoroborate with benzyl chlorides possessing electron-donating or electron-withdrawing substituents. Benzyl chloride was also successfully cross-coupled to potassium alkoxymethyltrifluoroborates derived from primary, secondary, and tertiary alcohols. [ABSTRACT FROM AUTHOR]

Cyclopropylmethyl palladium species can be accessed by Pd-catalyzed reaction of either cyclopropyl N-tosylhydrazone with halide or N-tosylhydrazone with cyclopropyl halide. In both approaches migratory insertion of Pd carbene is the key process. These transformations constitute new approaches toward 1,3-butadiene derivatives. [ABSTRACT FROM AUTHOR]

Abstract: On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure–activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K i =21.5nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K i(ant) =8.0nM comparable to 3. [Copyright &y& Elsevier]

Abstract: The addition reactions of α,β-unsaturated carbonyl compounds with dichloromethyl p-tolyl sulfoxide in the presence of NaHMDS or LDA resulted in the formation of adducts, 1-chlorocyclopropyl p-tolyl sulfoxides bearing a carbonyl group at the 2-position, in almost quantitative yields. The carbonyl group of the adducts was transformed to various ether groups to give 1-chlorocyclopropyl p-tolyl sulfoxides bearing an ether functional group at the 2-position in short steps. Treatment of these products with i-PrMgCl at low temperature afforded cyclopropylmagnesium carbenoids via the sulfoxide-magnesium exchange reaction. 1,5-Carbon–hydrogen insertion (1,5-CH insertion) reaction of the generated magnesium carbenoid intermediates took place to give 3-oxabicyclo[3.1.0]hexanes or bicyclo[3.1.0]hexanes bearing an ether group at the 4-position in moderate to good yields. When this procedure was carried out starting with enantiopure dichloromethyl p-tolyl sulfoxide, enantiopure 3-oxabicyclo[3.1.0]hexanes were obtained in good overall yields. These procedures provide a good way for the synthesis, including asymmetric synthesis, of multisubstituted 3-oxabicyclo[3.1.0]hexanes and bicyclo[3.1.0]hexanes from α,β-unsaturated carbonyl compounds and dichloromethyl p-tolyl sulfoxide in short steps. [Copyright &y& Elsevier]

Abstract: An investigation of the oxylipin chemistry of the temperate brown alga Cymathere triplicata led to the isolation of several secondary metabolites, cymatherelactone (1) and cymatherols A−C (2–4), the latter as their methyl ester derivatives (5–7), which contained cyclopentyl, cyclopropyl, epoxide and lactone rings. Their structures were elucidated using a combination of spectroscopic techniques and synthetic chemistry. Cymatherelactone (1), as well as R- and S-Mosher’s esters of its seco acid, exhibited moderate sodium channel blocking activity. [Copyright &y& Elsevier]

The synthetic scope of the reactions between benzenethiolate, 4-methoxybenzenethiolate, 2-naphthalenethiolate, and 2-pyridinethiolate anions with 1,3-dihalo-2,2-dimethylpropane was studied. These reactions render mono and disubstituted products from good to excellent yields. For all the substrates studied the monosubstituted halogenated product is the intermediate or the main product depending on the nature of the second leaving group. Aryl cyclopropyl sulfides were found as side products and their yields strongly depend on the base concentration (tert-BuOK). Finally, using neopentyl iodide as a model, the mechanism of these reactions was evaluated based on non-kinetic evidence, demonstrating that the reactions switch from SRN1 to polar SN2 according to the solvent employed. [ABSTRACT FROM AUTHOR]

We achieved the first total synthesis of a novel (�)-6′-methoxyretrojusticidin B, which was proposed as procumphthalide A, utilizing regiocontrolled benzannulation of an aryl(aryl′)-2,2-dichlorocyclopropylmethanol as the key step. �H NMR spectral data suggested that the structure of the synthesized product, 6′-methoxy�retrojusticidin B, was inconsistent with that of natural procumphthalide A. A computational study of the rotational barrier rationally supports the existence of a rigid chiral axis in 6′-methoxyretrojusticidin B. The revised structural elucidation of natural procumphthalide A was concluded to be 5′-methoxyretrochinensin. [ABSTRACT FROM AUTHOR]

An efficient AgOTf catalyzed tandem intramolecular transannulation of ((2-alkynyl)aryl)cyclopropyl ketones leading to the 2,3-dihydronaphtho[1,2-b]furans has been developed. The reaction features a regioselective alkyne hydration, cyclopropylketone-2,3-dyhydrofuran rearrangement, and benzannulation. The methodology gives direct access to the tricyclic core structure of biologically important 2,3-dihydronaphtho[1,2-b]furan natural products. [ABSTRACT FROM AUTHOR]

C31H27ZnFN3O9.5S, triclinic, P1̅ (no. 2), a = 10.6434(4) Å, b = 12.6191(4) Å, c = 12.8532(5) Å, α = 93.998(3)°, β = 109.121(3)°, γ = 112.773(3)°, V = 1465.16(9) Å3, Z = 2, Rgt( F) = 0.0354, wRref( F2) = 0.1012, T = 293 K. [ABSTRACT FROM AUTHOR]

An interesting catalytic dichotomy was discovered: switching between simple ligand-free catalysts leads to fundamentally different outcomes of reductive reaction between amines and α-carbonylcyclopropanes. Whereas a rhodium catalyst leads to the traditional reductive amination product, ruthenium catalysis enables a novel reaction of pyrrolidine synthesis via ring expansion. The protocols do not require an external hydrogen source and employ carbon monoxide as a deoxygenative agent. The developed methodologies are perfectly compatible with a number of synthetically important functionalities such as ester, carboxyl, bromo, and Cbz moieties. [ABSTRACT FROM AUTHOR]

The total synthesis of dictyopterene A was accomplished via an enantiomerically pure cyclopropylboronic ester building block. Crucial olefination steps were carried out employing the Julia-Kocienski as well as the Wittig reactions. The Matteson homologation was the final key step for the total synthesis. [ABSTRACT FROM AUTHOR]

The article discusses the discovery that litchi fruits have methylene cyclopropyl-glycine (MCPG), which is associated with hypoglycaemic encephalopathy. Topics covered include outbreaks of hypoglycaemic encephalopathy in children in Muzaffarpur district in Bihar, India, methylene cyclopropyl-alanine (MCPA) as an extrinsic toxin known to cause hypoglycaemic encephalopathy, and children's consumption of litchi fruits in Muzaffarpur.

Hydride abstraction from the gold (disilyl)ethylacetylide complex [( P)Au{η1-CCSi(Me)2CH2CH2SiMe2H}] ( P=P( tBu)2 o-biphenyl) with triphenylcarbenium tetrakis(pentafluorophenyl)borate at −20 °C formed the cationic gold (β,β-disilyl)vinylidene complex [( P)AuCCS i(Me)2CH2CH2Si(Me)2]+B(C6F5)4− with ≥90 % selectivity. 29Si NMR analysis of this complex pointed to delocalization of positive charge onto both the β-silyl groups and the ( P)Au fragment. The C1 and C2 carbon atoms of the vinylidene complex underwent facile interconversion (Δ G≠=9.7 kcal mol−1), presumably via the gold π-disilacyclohexyne intermediate [( P)Au{η2- CCSi(Me)2CH2CH2Si (Me)2}]+B(C6F5)4−. [ABSTRACT FROM AUTHOR]

All of the Group IV elements, C, Si, Ge, Sn and Pb, form four tetrahedrally disposed bonds and could be considered as replacements for each other. Because the atomic radius increases linearly with increasing row number, this replacement can also be considered as a probe of steric effects. The use of silicon, with its high natural abundance and non-toxic nature, has received the most attention. Examples of silicon-for-carbon exchange can be found for all major classes of insecticides, including carbamates, phosphates, pyrethroids, as well as DDT and juvenile hormone analogs. Generally, the silicon analogs retain insecticidal activity. A silicon analog of MTI-800 (dimethyl-4-ethoxyphenyl-I-(3-(4-fluoro-3-phenoxyphenyl)propyl)silane) is a broad spectrum insecticide. This silane was used as a starting point for building new silane analogs as potential insecticides. Two analogs were particularly noteworthy. A silane with a cyclopropyl group was found to be non-toxic to Trichoplusia ni (cabbage looper) while the corresponding carbon compound was a potent insecticide. An analog containing a silicon-hydrogen bond, a structural feature reported to be unstable in vivo, was found to be significantly insecticidal both topically and in foliar tests. The latter compound suggests that biologically active silanes can encompass broader structural types than previously anticipated. [ABSTRACT FROM AUTHOR]

Optimisation of activity within the structural constraints defined by the preceding work, by varying the substituents on phenyl in the acid fragment (10 variations), the nature of the group fulfilling the dimethyl function (three variations), the central linking group (four variations) and the presence or absence of a 4-fluoro substituent in the alcohol fragment, has led to achiral compounds as active as bioresmethrin against houseflies and mustard beetles. Statistical analysis of the effects has shown that particular combinations, for instance the cyclopropyl form of dimethyl with a central E-alkene group (but not a central ether group), lead to higher activity than expected. 4-Fluoro substitution enhances activity more strongly against mustard beetles. Difluorocyclopropyl compounds are on average slightly more active than cyclopropyl analogues. [ABSTRACT FROM AUTHOR]

A new one-pot synthesis of e-spirocyclopropyl-e-caprolactones has been implemented via the reaction between vinylarenes, EtAlCl2 and dimethyl adipate catalyzed by Cp2ZrCl2 in 60% yield. [ABSTRACT FROM AUTHOR]