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General routes for the synthesis of 1,3-oxazin-4-ones are discussed, with particular attention paid to recent developments in the field. The syntheses of amine functionalised cyclopropyl carbinols via a hydride-mediated reduction of various 5-chloroethyl-1,3-oxazin-4-enones in moderate to good yield are disclosed. This new method provides an opportunity to access greater structural diversity within these useful synthetic building blocks. [ABSTRACT FROM AUTHOR]

A convenient copper-catalyzed approach has been developed for the synthesis of substituted spiro-fused pyrazolin-5-ones from readily available cyclopropyl O-acyl ketoximes via an intramolecular NN bond formation reaction. These catalytic reactions proceed in excellent yields with a broad scope. [ABSTRACT FROM AUTHOR]

The synthesis of chiral cyclopropyl carbocyclic purine nucleoside analogues via the highly enantioselective intramolecular cyclopropanation reactions has been reported. With a chiral ruthenium(II)-phenyloxazoline complex as the catalyst, cyclopropyl carbocyclic purine nucleoside analogues containing three contiguous stereocenters were obtained with up to 99% yield and 99% ee. Furthermore, a chiral cyclopropyl carbocyclic adenosine nucleoside having anti-BLV activity could be synthesized in a concise manner using this strategy. [ABSTRACT FROM AUTHOR]

An efficient allylation and butenylation of N-alkoxycarbonyl-2-tributylstannyl-1,3-oxazolidines derived from ( S)-vinylglycinol or ( S)-styrylglycinol is described. After conversion of the stannylated azadienes into stannylated dienyl oxazolidinones, a ring-closing metathesis generates dehydropiperidine or dehydroazepane; both are interesting scaffolds for the synthesis of polyfunctionnalized piperidines or azepanes. Whereas the dehydropiperidine synthesis was found to be selective regardless of the Grubbs catalyst used, we found that Grubbs II catalyst induced partial double bond isomerization in the dehydroazepane series. In addition, when allyltrimethylsilane was used in the ring-opening reactions of N-alkoxycarbonyl-2-tributylstannyl-1,3-oxazolidines, cyclopropyl derivatives were selectively obtained. [ABSTRACT FROM AUTHOR]

An efficient approach for the synthesis of highly functionalized pyrroles has been developed by a Pd(TFA)2-catalyzed tandem heterocyclization of 1-(1-alkynyl)cyclopropyl oxime derivatives under mild conditions. The reaction first proceeded via an intramolecular nucleophilic attack followed by a ring-opening process and then intermolecular nucleophilic attack as well as protonation to afford the desired products in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

A new series of 4-cyclopropyl-5-(2-fluorophenyl)arylhydrazono-2,3-dihydrothiazole derivatives was synthesized via the reaction of prepared thiosemicarbazones with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)ethanone in the presence of Et3N as a catalyst through a semi Hantzsch cyclization. The optimized reaction conditions for this one-pot reaction were achieved. The products were obtained in short reaction times, high yields and high purities. Antioxidant activity of products was evaluated using DPPH (2,2-diphenyl-2-picrylhydrazyl) and ABTS 2,2-azinobis(3-ethylbenzothiazoline-sulfonate) assays. Products showed higher antioxidant activity using the ABTS method. Compounds5cand5gshowed lower IC50values compared with ascorbic acid as a standard. Compounds5a–5hpossessed moderate to high antioxidant activity by both methods. Also, antibacterial activity of5a–5hwas evaluated against gram-positive and gram-negative bacterial strains. None of the compounds inhibitedA. hydrophila, while they had moderate to low inhibitory activity against other tested bacterial strains. [ABSTRACT FROM AUTHOR]

Reactions of anhydrous lanthanide trichlorides, LnCl3 (Ln = Nd, Sm, Ho), with 3 equiv. of lithium-cyclopropylethinylamidinates, Li[c-C3H5–C≡C–C(NR)2] (1a: R = cyclohexyl (Cy), 1b: R = iPr), afforded the new homoleptic lanthanide(iii) tris(cyclopropylethinylamidinate) complexes [c-C3H5–C≡C–C(NCy)2]3Sm (2a) and [c-C3H5–C≡C–C(NiPr)2]3Ln (Ln = Nd (2b), Sm (2c), Ho (2d)) as air- and moisture-sensitive crystalline solids in moderate to good isolated yields (45–79%). The formation of unsolvated, homoleptic Ln(iii) tris(cyclopropylethinylamidinate) was confirmed by an X-ray diffraction study of the holmium derivative [c-C3H5–C≡C–C(NiPr)2]3Ho (2d). EI mass spectra of the new rare-earth metal amidinates indicated a significant volatility. An initial catalysis study revealed that these complexes catalyze the addition of terminal alkynes to carbodiimides to give propiolamidines of the type R–C≡C–C(=NR′)(NHR′). The molecular structure of N,N′-dicyclohexyl-phenylpropiolamidine, Ph–C≡C–C(NCy)(NHCy) (4), was also determined by X-ray diffraction. [ABSTRACT FROM AUTHOR]

A novel 1,2,4-triazole compound was synthesized and the chemical structure was confirmed by 1H NMR, MS and elemental analyses. The crystal structure of the 1,2,4-triazole (C13H14FN3S, Mr = 263.33) has been determined by single-crystal X-ray diffraction. The compound crystallizes in the monoclinic system, space group P2(1)/c with a = 7.5179(15), b = 19.638(4), c = 8.4922(17)Å, α = 90 °, β = 98.11(3)°, γ = 90°, V = 1241.2(4)Å3, Z = 4,. The herbicidal activity of 1,2,4-triazole was determined and the results showed the title compound displayed excellent herbicidal activity. Theoretical calculations of 1,2,4-triazole was carried out with B3LYP/6-31G (d,p) approximation. The optimized geometric parameters obtained by using DFT method show the best agreement with the experimental data. [ABSTRACT FROM AUTHOR]

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5- position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction. [ABSTRACT FROM AUTHOR]

The first total synthesisof nardoaristolone B, a nor-sesquiterpenoidwith an unusual fused ring system and having protective effects onthe injury of neonatal rat cardiomyocytes, has been accomplished.Stereoselective synthesis of its novel analogues inlcuding exo-cyclopropyl ring fusion is also part of this disclosure.In addition, an alternate and more efficient one-step method to makea 3/5/6 tricyclic ring system using the Robinson annulation methodhas been developed toward the generation of a library of compoundsaround this skeleton. [ABSTRACT FROM AUTHOR]

Abstract: Chiral spiropyrazolinepenicillanates were obtained in a stereoselective fashion via 1,3-dipolar cycloaddition reactions of 6-alkylidenepenicillanates with diphenyldiazomethane, phenyldiazomethane, and diazomethane. Microwave-induced ring contraction of spiro-1-pyrazoline-β-lactams leading to chiral spirocyclopropylpenicillanates is also described. [Copyright &y& Elsevier]

Abstract: A series of fused cyclopropyl-4,5-dihydropyridazin-3-one (3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one) phenoxypiperidine analogs was designed and synthesized, leading to the identification of (1R,6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a) as a second-generation pyridazin-3-one H3R antagonist. Compound R,S-4a was a potent H3R functional antagonist in vivo in the rat dipsogenia model, demonstrated potent wake activity in the rat EEG/EMG model, and enhanced short-term memory in the rat social recognition memory model at doses as low as 0.03–0.3mg/kg po. [Copyright &y& Elsevier]

Abstract: A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized (1H NMR, 13C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC values in the range 7.32–136.10 μM against Mycobacterium tuberculosis H37Rv. Eight compounds were further subjected to cytotoxic studies. Furthermore, the title compounds were screened for antibacterial activity against Staphylococcus aureus ATCC 29213 (gram positive) and Escherichia coli ATCC 25922 (gram negative) bacteria. Many of these compounds exhibited MIC values in the range 0.44–34.02 μM. Compound 3f was found to be the most active with an MIC of 0.44 and 0.8 μM respectively against both the strains. In general, the antibacterial activity of title compounds was more prominent. [Copyright &y& Elsevier]

Abstract: Direct synthesis of 1,1-disubstitued 1,3-butadienes has been efficiently realized from the cross-coupling of cyclopropylmethyl N-tosylhydrazones with aromatic bromides by means of PdCl2(MeCN)2 as catalyst. 1,1,4-Trisubstitued 1,3-butadiene derivatives were obtained in up to 70% yields through a one-pot procedure catalyzed by Pd(OAc)2 in the presence of excessive amount of aromatic bromides. The present methodology provides an easy and efficient route to multisubstituted 1,3-butadienes. [Copyright &y& Elsevier]

Abstract: The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1′ region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2′ substituent of chromane–HEA(s) with polar substituents provided improvements in the compound’s in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane. [Copyright &y& Elsevier]

A novel series of ( S)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy. Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 ( DPP-4) inhibitors; among them, the cyclopropyl-substituted phenylalanine derivative 11h displayed the most potent DPP-4 inhibitory activity with an IC50 value of 0.247 μ m. In addition, molecular docking analysis of the representative compounds 11h, 11k, and 15a were performed, which not only revealed the impact of binding modes on DPP-4 inhibitory activity but also provided additional methodological values for design and optimization. [ABSTRACT FROM AUTHOR]

Abstract: 1,3-Dipolar cycloadditions of dialkyl-substituted 2-benzylidenecyclopropane-1,1-dicarboxylates and a number of C-carbamoyl nitrones proceed with high efficiency and selectivity with the formation of single isomeric spiro[cyclopropane-1,4-isoxazolidine] cycloadduct. Obtained cycloadducts easily undergo cyclopropyl ring opening–cyclization to form new β-lactams fused with isoxazolidine ring in high yields. [Copyright &y& Elsevier]

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]

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]

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]

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]

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]

Abstract: seco-Iso-cyclopropylfurano[e]indoline-trimethoxyindole 1 and seco-cyclopropylfurano[f]quinoline-trimethoxyindole 2 are potent cytotoxic agents. Previous synthesis of these compounds was inefficient and the approach required separation of a mixture containing the isomeric indoline and quinoline intermediates 11 and 12, formed from radical cyclization of allylic bromide 10. Reported herein is an efficient and selective synthesis of either intermediate 11 or 12, thus product 1 or 2, as needed. The conditions of the Stobbe condensation, bromination, 5-exo-trig radical cyclization, amine-carboxylic acid coupling, and debenzylation were optimized for multi gram scale. As a result, the reaction times were shortened, the products were readily isolated, and the yields and purity improved. [Copyright &y& Elsevier]

An efficient synthesis of prasugrel, a thienopyridine ADP-receptor antagonists, is described. A thienopyridine intermediate was prepared by N-protection, boric acid substitution and N-substitution. After acid hydrolysis of the methyl ether and subsequent acetylation, prasugrel was obtained with a total yield of 50% after seven linear steps from 4,5,6,7-tetrahydrothieno [3,2-c]pyridine and 2-bromo-1-cyclopropyl-2-(2- fluorophenyl)ethan-1-one as raw materials. [ABSTRACT FROM AUTHOR]

Abstract: Cyclopropyl analogues of melatonin can be readily synthesized in high yields by Rh(II)-catalysed decomposition of aryldiazoacetates in the presence of N-vinylacetamide or vinyl acetate. The reaction is highly trans selective. [Copyright &y& Elsevier]

Abstract: The first efficient total syntheses of 3((1R,2R)- and 3((1S,2R)-2-(12-methyltridecyl)cyclopropyl)propanoic acid have been achieved following a chelation controlled modified Simmon–Smith cyclopropanation, Wittig reaction, Horner–Wadsworth–Emmons olefination, and p-toluenesulfonyl hydrazide catalyzed hydrogenation as key reactions in good overall yield. [Copyright &y& Elsevier]

The article focuses on the study on the efficiency of regioselective synthesis of 6,7-dihydro-5H-pyrrolo[1,2-c][1,3]thiazol-4-ium bromides IIIa-IIIc compounds. The study examines the mechanism of formation of compounds and was being synthesized including 4-cyclopropyl-substituted 2-aminothiazolium bromide into 3-amino-6,7-dihydro-5H-pyrrolo[1,2-c]- [1,3]thiazolium bromide. Moreover, the proton nuclear magnetic resonance (NMR) spectroscopy were also studied.

The use of a base affords pyranosides, whereas silver salts gives the corresponding bromooxepines. [ABSTRACT FROM AUTHOR]

A regioselective synthesis of title compounds (II) and (IV) in good to excellent yields from alkynylcyclopropanecarboxylic acid derivatives (I) and (III) is reported. [ABSTRACT FROM AUTHOR]

Cyclopropyl Grignard reagents react with carbonyl compounds in the presence of diethyl phosphite to give homoallylic bromides. [ABSTRACT FROM AUTHOR]