New synthesis of β-lactams

α-Methylene-β-lactams 3 were synthesized from the various 2-bromoallylamine derivatives 2 using a catalytic amount of Pd(OAc)₂ or PD(acac)₂ and PPh₃, under 1–4 atom pressure of CO in good yields. Similarly, α-alkylidene-β-lactams 20 were synthesized from 3-alkyl-2-bromoallylamines 19, which were easily prepared from the olefins 14, in the same manner.     

Photochemistry of 5.6-epoxy-1,3-dienes : Influence of a 7-hydroxy substituent

Triplet sensitization of the 7-hydroxy-5,6-epoxy-1,3-diene 10 causes cleavage of the C(5),0 epoxide bond followed by the formation of the three isomers 11–13 or induces scission of the C(6), C(7) bond followed by the formation of the aldehyde 14 and the bicyclo[3.2.0]heptanols 15 and 16. However, irradiation of the corresponding acetate 18 gives only C(5),0 epoxide bond scission (18 → f) followed by the cyclization process f → 19, the 1,2-Me shifts f → 20, 21 and the γ-H abstraction f → g leading to the cyclopropane formation g → 22.     

Diels-alder reactions of substituted maleic anhydrides with 1-vinylcoclohexane: Stereospecific formation of a bicyclic intermediate useful for syntheses of clerodane diterpenes

The Diels-Alder reaction of 1-vinylcyclohexene with aconitic anhydride gives the adduct 5b which has the reversed stereochemistry of that predicted by Alder's endo rule. On the other hand, reactions with chloromethylmaleic anhydride and citraconic anhydride afford endo-adducts 23 and 24, respectively. Adduct 23 has the appropriate stereochemistry and functionality for the syntheses of clerodane and related diterpenes.     

Synthetic studies on terpenic compounds—XI : Stereospecific total synthesis of portulal,

A stereospecific total synthesis of portulal 1 has been accomplished starting from the Diels-Alder adduct 2 from chloromethylmaleic anhydride and 1-vinylcyclohexene. Firstly 2 was converted by an efficient sequence of reactions to perhydroazulenoid lactone 5, which possesses the correct relative configuration with respect to three chiral centers out of the four present in 1. The fourth chiral center at C-6 was introduced stereospecifically together with the one-carbon substituent at C-4 by the ring formation between C-4 and C-6, and its cleavage to give an exomethylene lactone 35. At this stage the stereochemical validity of the crucial intermediate 35 was confirmed by chemical correlation with the hydroxy lactone 37 which was derived from natural 1 through a systematic degradation. Then 35 was transformed to 37 and the synthesis continued further by using 37 as a relay compound to afford 1.     

Sesquiterpene constituents of two liverworts of genus diplophyllum: Novel eudesmanolides and cytotoxicity studies for enantiomeric methylene lactones

The steam distillates (or hexane extracts) of the liverworts Diplophyllum albicans (L.) Dum. and D. taxifolium (Wahl.) Dum. are largely a mixture of sesquiterpenes. Both species elaborate, among the hydrocarbons, mainly ent-α-selinene (8a) and ent-selina-4,11-diene (8b) together with anastreptene (1) and β-elemene (9). The major component of each essential oil was diplophyllin (10), a novel ent-eudesmanolide. The structure of diplophyllin was established by correlation with tetrahydro-isoalantolactone (17). In addition, the enantiomers of diplophyllin and diplophyllolide-A (16) were obtained on acid isomerization of isoalantolacetone (14a). Diplophyllin shows significantly greater activity against human epidermoid carcinoma (KB cell culture, ED₅₀? 8 μ $\text{g}\text{ml}$) than its enantiomer: the first demonstration (to our knowledge) of optical selectivity for this type of cytotoxicity. Among the more polar constituents of D. albicans were 9α-acetoxy-diplophyllin, and several sesquiterpene alcohols including albicanol (22).     

Cyclic cross-conjugated hydrocarbons having inserted p-quinoid ring—I : Diphenyl-p-tropylphenylmethyl cation formed on an attempted preparation of 1-cycloheptatrienylidene-4-diphenylmethylidene-2,5-cyclohexadiene

In connection with the synthetic studies of the cross-conjugated system 2, p-(diphenylhydroxymethyl)phenyltropolidene (13)* was prepared. On treatment with CF₃COOH, 13 transformed to an aryltropylium ion (15) via an unstable blue colored compound. Based on NMR spectroscopy and some chemical properties the structure of the pigment is assumed to be diphenyl-p-tropylphenylmethyl cation (16) rather than the primarily anticipated cross-conjugated hydrocarbon 9,9-diphenyl[1.6.7]quinarene (6).     

Constituents of morphologically similar sponges : Aplysina and smenospongia species

Compounds from the marine sponge Smenospongia aurea have been isolated and characterized as 5-bromo- and 5,6-dibromo-N,N-dimethyltryptamines (1 and 2), aureol (3), and two new aplysinopsin derivatives (6-bromoaplysinopsin and 6-bromo-4'-N-demethylaplysinopsin, 4 and 5, respectively). Morphologically similar species from the Caribbean have been surveyed and found to contain either mixtures of these metabolites or bromotyrosine-derived compounds. ¹H NMR spectra of bromoindole-containing metabolites are discussed.     

Concerted cycloaddition of chlorosulfonyl isocyanate to α-pinene stepwise rearrangement of the β-lactam cycloadduct to a γ-lactam

Chlorosulfonyl isocyanate adds to α-pinene in concerted fashion to give the unrearranged N-chlorosulfonyl-β-lactam 2 (75%). Thermolysis of cycloadduct 2 affords the rearranged N-chlorosulfonyl-γ-lactam 6 (60%) via a sequence of transient carbonium ions (45). Reductive hydrolysis of 2 and 6 gave, respectively, the NH-β-lactam 3 (70%) and the NH-γ-lactam 7 (70%). Proof of structure of the rearranged γ-lactams 6 and 7 are provided, respectively, by X-ray crystallographic analysis and the application of the Eu(dpm)₃ NMR shift reagent.     

A structural study of new tetrakis(1H-pyrazol-1-yl)methanes

Tetrakis(1H-pyrazol-1-yl)methanes are very rare compounds of which only two are known: the unsubstituted 1 obtained classically by Hückel in 1937 from carbon tetrachloride and prepared again several times and the 3,5-dimethyl substituted 2 obtained serendipitously by Pombeiro in 2009. We have now extended this group to include four new derivatives 8, 9, 11 and 12 bearing methyl groups. The X-ray crystal structure of the four compounds has been determined. They have been studied by NMR both in solution (¹H, ¹³C, ¹⁵N) and in the solid state (¹³C and ¹⁵N). DFT calculations of the six compounds (geometries, energies and absolute shieldings) have been used to discuss the experimental observations.     

Photochemistry of β, γ-unsaturated ketones-V: The direct irradiation of some γ-phenyl β, γ-enones

The photochemistry of some members of the two series of γ-phenyl substituted acyclic β, γ-unsaturated ketones 1 and 2 upon direct irradiation with γ 310nm has been investigated, viz 1c–1h and 2b+2c.The alkyl substituted (E)-5-phenyl-4-penten-2-ones 1c–1h yield the corresponding 1,3-acyl shift products and (Z)-isomers, and 1g and 1h in addition two decarbonylated products. 2b only yields the (Z)-isomer and some benzaldehyde, but 2c yields the 1,3-acyl shift product, the ODPM product, three hydrocarbons formed by disproportionation of the allyl radical, and some benzaldehyde. The β-phenyl β, γ-UK 3a proved to be photostable. The 1,3-acyl shift products of 1c–1h result mainly from the singlet excited state in a cage radical process. The exclusive formation of the (E)-configuration of the 1,3-acyl shift product is explained in terms of conformational preference of the intermediate allyl radical. It is proposed that the formation of the (Z)-isomer proceeds from ¹T(π -π^*) which is populated according to

. Evidence is presented which supports the proposed mechanism.The β,γ-UK 2b containing a benzoyl moiety leads to a higher degree of (E)-(Z) isomerization than the corresponding 1d which has an acetyl moiety.The triplet energies of (E)- and (Z)-1h are 56 and ca 70 kcal/mol respectively.     

Synthesis of the enantiomers of 4-substituted γ-lactones with known absolute configuration

The highly pure enantiomers of several 4-alkyl (or alkenyl)-γ-lactones of known absolute configuration were synthesized from glutamic acid enantiomers. The key step is selective tosylate displacement rather than ring opening of the lactone tosylate (7→1) by lithium dialkylcuprate or dialkenylcuprate. The enantiomeric purity of synthesized γ-caprolactone was confirmed within the limitations of Pirkle's chiral solvating agent. The enantiomers of synthesized (Z)-6-dodecen-4-olide were used for reference to determine the enantiomeric composition of the pheromone isolated from the black-tailed deer.     

Thermal analysis graphite intercalation compounds with dichlorides of some d-elements: A.S. Skoropanov,G.S. Petrov,A.A. Vecher,Yu.N. Novikov and M.E. Vol'pin,Thermochim. Acta, 90 (1985) 339-342

Kinetic and thermodynamic aspects of the axial base dissociation of solid Co(salen) (X-py) complexes, X = H (1), 3-Me (2), 4-Me (3), 3,4-Me₂ (4), 3,5-Me₂ (5), 3-NH₂ (6), 3-Cl (7), 3-CN (8), 4-CN (9), have been investigated by means of TG-DSC and isothermal weight-loss measurements. These adducts endothermically dissociate the axial base giving rise to the oxygen-active Co(salen) complex. The axial base dissociation reactions fit the contracting disc equation and the kinetic compensation effect is observed for all the adducts excepting Adducts 4–6. For the remaining adducts the kinetic and thermodynamic stabilities of the Co-(X-py) bond are found to increase linearly with increasing Hammett's substitution constants of X except for Adducts 3 and 9. These results are discussed in terms of the σ and π interactions between cobalt(II) and substituted pyridine. Factors dominating the kinetic bond stability are briefly discussed.     

Rearrangement during cyclisation of some 3-(2-pyrrolyl) propionic acids and related compounds

Cyclisation of the title compounds leads to mixtures of the expected 4H-cyclopental[b]pyrrol-4-ones (1), the corresponding 6-ones (3) by a single rearrangement, and the cyclopenta[c]pyrrol-4-ones (4) by a double rearrangement, the proportions depending upon the substituents.The ¹H NMR spectra of 2-methyl-4H-cyctopenta[b]thiophen-6-one (3f) shows 6J long range $\text{CH}{}_3\text{CH}{}_2$ coupling, but this is absent in the corresponding pyrroles (3c,d). The ¹³C spectra of 1 and 3 cannot be interpreted on the basis of substituent chemical shifts in pyrroles and thiophens, and are clearly -CH = CH-X (X = NMe, NPh, S) bridged derivatives of cyclopent-2-enone.     

Reductive coupling of aliphatic cyclic imides and ω-amidoesters with benzophenones by low-valent titanium: Synthesis of 5-diarylmethylene-1,5-dihydropyrrol-2-ones, 6-diarylmethyl-2-pyridones,and ω-(diarylmethylene)lactams

The reductive coupling of cyclic imides and ω-amidoesters with benzophenones by Zn-TiCl₄ in THF and subsequent acid-catalyzed dehydration gave 5-diarylmethylene-1,5-dihydropyrrol-2-ones A, 6-diarylmethyl-2-pyridones B, and ω-(diarylmethylene)lactams C. In a similar manner, 3-((benzyloxy)carbonyl)amino substituted A, B, and C were synthesized from the corresponding 3-((benzyloxy)carbonyl)amino cyclic imides and ω-((benzyloxy)carbonyl)amino-ω-amidoesters prepared from L-aspartic and L-glutamic acids. In addition, 4- and 5-((benzyloxy)carbonyl)amino substituted C were also obtained by the same procedures from 2-((benzyloxy)carbonyl)amino-ω-amidoesters prepared from L-asparagine and L-glutamine, respectively.     

Total synthesis,reactivity, and structural clarification of lindenatriene

The synthesis of lindenatriene (1) and iso-lindenatriene (12) were achieved, along with the des-hydroxy model compounds (10 and 18, respectively), and compared to reported ¹H NMR spectra in the literature (1a and 10a). These comparisons clarify the correct initial assignment of lindenatriene (1) as well as its instability and propensity to isomerize into the more thermodynamically favored iso-lindenatriene (12).     

Design,synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

A series of novel N-1 and C-3 substituted indole derivatives (5a–f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC₅₀ of 6.49 μM and 5c with an IC₅₀ of 33.69 μM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively.     

Resolution,absolute configuration and antifilarial activity of coumarinyl amino alcohols

The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-l-proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(?)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(?)-9 and (S)-(+)-10, (R)-(?)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Energy and angular differential cross sections for K + NO2 charge transfer reactions

Doubly differential cross sections, in energy and angle, are reported for the electron transfer reaction between potassium and nitrogen dioxide in a crossed beam apparatus at relative collision energies between 2.7 and 30.8 eV. The formation of NO^?₂ in its ground ¹A₁ and excited ³B₁ state has been observed. Theoretical consideration of these processes indicates that bond bending during the collision has a stronger influence on ion-pair formation than bond stretching. At the lower collision energies most of the excess energy is converted into internal energy of NO^?₂.