Enantioselective formal synthesis of (+)-madangamine A

An enantioselective formal synthesis of the marine alkaloid madangamine A using phenylglycinol-derived lactam 1 as the starting enantiomeric scaffold is reported. The synthesis involves the construction of the C-9 substituted diazatricyclic ABC core and the final closure of D and E rings from the polyunsaturated skipped intermediate 19

A Straightforward Synthesis of Functionalized cis-Perhydroisoquinolin-1-ones

Base-catalyzed annulation reactions of 5,6-dihydro-2(1H)-pyridones with Nazarov-type reagents are reported. The effect of the solvent polarity and the concentration of the reagents is studied. The process involves two successive Michael additions and stereoselectively provides functionalized cis-perhydroisoquinolin-1-ones

Stereocontrolled annulations of indolo[2,3-a]quinolizidine-derived lactams with a silylated Nazarov reagent. Access to allo and epiallo yohimbine-type derivatives

The facial selectivity of double Michael addition reactions of the silylated Nazarov reagent 4 to unsaturated indolo[2,3-a]quinolizidine lactams 3 has been studied. Pentacyclic 3-H/15-H trans adducts 5 are generated from Nind -unsubstituted lactams, but the corresponding cis isomers 6 are formed when the indole nitrogen has a tert-butyloxycarbonyl (Boc) substituent. This reversal in the facial selectivity of the annulation has been rationalized by means of theoretical calculations, which indicate that the initial nucleophilic attack under stereoelectronic control is hampered by the presence of the bulky Boc group. The synthetic usefulness of the pentacyclic Nazarov-derived adducts is demonstrated by their conversion into allo and epiallo yohimbine-type targets

Inclusive J/ψ production at midrapidity in pp collisions at √s=13 TeV

We report on the inclusive $\text {J}/\psi$ production cross section measured at the CERN Large Hadron Collider in proton–proton collisions at a center-of-mass energy $\sqrt{s}~=~13$ TeV. The $\text {J}/\psi$ mesons are reconstructed in the $\text {e}^{+}\text {e}^{-}$ decay channel and the measurements are performed at midrapidity ($|y|<0.9$) in the transverse-momentum interval $0<p_{\mathrm{T}} <40$ GeV/$c$, using a minimum-bias data sample corresponding to an integrated luminosity $L_{\text {int}} = 32.2~\text {nb}^{-1}$ and an Electromagnetic Calorimeter triggered data sample with $L_{\text {int}} = 8.3~\mathrm {pb}^{-1}$. The $p_{\mathrm{T}}$-integrated $\text {J}/\psi$ production cross section at midrapidity, computed using the minimum-bias data sample, is $\text {d}\sigma /\text {d}y|_{y=0} = 8.97\pm 0.24~(\text {stat})\pm 0.48~(\text {syst})\pm 0.15~(\text {lumi})~\mu \text {b}$. An approximate logarithmic dependence with the collision energy is suggested by these results and available world data, in agreement with model predictions. The integrated and $p_{\mathrm{T}}$-differential measurements are compared with measurements in pp collisions at lower energies and with several recent phenomenological calculations based on the non-relativistic QCD and Color Evaporation models.publishedVersio

Inclusive quarkonium production in pp collisions at √s = 5.02 TeV

This article reports on the inclusive production cross section of several quarkonium states, $\textrm{J}/\psi$, $\psi \mathrm{(2S)}$, $\Upsilon \mathrm (1S)$, $\Upsilon \mathrm{(2S)}$, and $\Upsilon \mathrm{(3S)}$, measured with the ALICE detector at the LHC, in pp collisions at $\sqrt{s} = 5.02$ TeV. The analysis is performed in the dimuon decay channel at forward rapidity ($2.5< y < 4$). The integrated cross sections and transverse-momentum ($p_{\textrm{T}}$) and rapidity ($y$) differential cross sections for $\textrm{J}/\psi$, $\psi \mathrm{(2S)}$, $\Upsilon \mathrm (1S)$, and the $\psi \mathrm{(2S)}$-to-$\textrm{J}/\psi$ cross section ratios are presented. The integrated cross sections, assuming unpolarized quarkonia, are: $\sigma _{\textrm{J}/\psi }$ ($p_{\textrm{T}} <20$ GeV/c) = 5.88 ± 0.03 ± 0.34$~\mu$b, $\sigma _{\psi \mathrm{(2S)}}$ ($p_{\textrm{T}} <12$ GeV/c) = 0.87 ± 0.06 ± 0.10$~\mu$b, $\sigma _{\Upsilon \mathrm (1S)}$ ($p_{\textrm{T}} <15$ GeV/c) = 45.5 ± 3.9 ± 3.5 nb, $\sigma _{\Upsilon \mathrm{(2S)}}$ ($p_{\textrm{T}} <15$ GeV/c) = 22.4 ± 3.2 ± 2.7 nb, and $\sigma _{\Upsilon \mathrm{(3S)}}$ ($p_{\textrm{T}} <15$ GeV/c) = 4.9 ± 2.2 ± 1.0 nb, where the first (second) uncertainty is the statistical (systematic) one. For the first time, the cross sections of the three $\Upsilon$ states, as well as the $\psi \mathrm{(2S)}$ one as a function of $p_{\textrm{T}}$ and $y$, are measured at $\sqrt{s} = 5.02$ TeV at forward rapidity. These measurements also significantly extend the $\textrm{J}/\psi$ $p_{\textrm{T}}$ reach and supersede previously published results. A comparison with ALICE measurements in pp collisions at $\sqrt{s} = 2.76$, 7, 8, and 13 TeV is presented and the energy dependence of quarkonium production cross sections is discussed. Finally, the results are compared with the predictions from several production models.publishedVersio

First measurements of N-subjettiness in central Pb-Pb collisions at √sNN = 2.76 TeV

The ALICE Collaboration reports the first fully-corrected measurements of the N-subjettiness observable for track-based jets in heavy-ion collisions. This study is performed using data recorded in pp and Pb-Pb collisions at centre-of-mass energies of s√ = 7 TeV and sNN−−−√ = 2.76 TeV, respectively. In particular the ratio of 2-subjettiness to 1-subjettiness, τ2/τ1, which is sensitive to the rate of two-pronged jet substructure, is presented. Energy loss of jets traversing the strongly interacting medium in heavy-ion collisions is expected to change the rate of two-pronged substructure relative to vacuum. The results are presented for jets with a resolution parameter of R = 0.4 and charged jet transverse momentum of 40 ≤ pT,jet ≤ 60 GeV/c, which constitute a larger jet resolution and lower jet transverse momentum interval than previous measurements in heavy-ion collisions. This has been achieved by utilising a semi-inclusive hadron-jet coincidence technique to suppress the larger jet combinatorial background in this kinematic region. No significant modification of the τ2/τ1 observable for track-based jets in Pb-Pb collisions is observed relative to vacuum PYTHIA6 and PYTHIA8 references at the same collision energy. The measurements of τ2/τ1, together with the splitting aperture angle ∆R, are also performed in pp collisions at s√ = 7 TeV for inclusive jets. These results are compared with PYTHIA calculations at s√ = 7 TeV, in order to validate the model as a vacuum reference for the Pb-Pb centre-of-mass energy. The PYTHIA references for τ2/τ1 are shifted to larger values compared to the measurement in pp collisions. This hints at a reduction in the rate of two-pronged jets in Pb-Pb collisions compared to pp collisions.publishedVersio

Anisotropic flow of identified hadrons in Xe-Xe collisions at √sNN = 5.44 TeV

Measurements of elliptic (v2) and triangular (v3) flow coefficients of π±, K±, p+$\overline{\mathrm{p}}$, ${\mathrm{K}}_{\mathrm{S}}^0$, and Λ+$\overline{\Lambda}$ obtained with the scalar product method in Xe-Xe collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.44 TeV are presented. The results are obtained in the rapidity range |y| < 0.5 and reported as a function of transverse momentum, pT, for several collision centrality classes. The flow coefficients exhibit a particle mass dependence for pT < 3 GeV/c, while a grouping according to particle type (i.e., meson and baryon) is found at intermediate transverse momenta (3 < pT < 8 GeV/c). The magnitude of the baryon v2 is larger than that of mesons up to pT = 6 GeV/c. The centrality dependence of the shape evolution of the pT-differential v2 is studied for the various hadron species. The v2 coefficients of π±, K±, and p+$\overline{\mathrm{p}}$ are reproduced by MUSIC hydrodynamic calculations coupled to a hadronic cascade model (UrQMD) for pT < 1 GeV/c. A comparison with vn measurements in the corresponding centrality intervals in Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV yields an enhanced v2 in central collisions and diminished value in semicentral collisions.publishedVersio

KS0 - and (anti-) Λ -hadron correlations in pp collisions at √s=13 TeV

Two-particle Azimuthal correlations are measured with the ALICE apparatus in pp collisions at s√=13s=13 TeV to explore strangeness- and multiplicity-related effects in the fragmentation of jets and the transition regime between bulk and hard production, probed with the condition that a strange meson (KS0KS0) or baryon (ΛΛ) with transverse momentum pT>3pT>3 GeV/cc is produced. Azimuthal correlations between kaons or ΛΛ hyperons with other hadrons are presented at midrapidity for a broad range of the trigger (3<ptriggT<203<pTtrigg<20 GeV/cc) and associated particle pTpT (1 GeV/cc <passocT<ptriggT<pTassoc<pTtrigg), for minimum-bias events and as a function of the event multiplicity. The near- and away-side peak yields are compared for the case of either KS0KS0 or ΛΛ(Λ¯¯¯¯Λ¯) being the trigger particle with that of inclusive hadrons (a sample dominated by pions). In addition, the measurements are compared with predictions from PYTHIA 8 and EPOS LHC event generators.publishedVersio

Experimental Evidence for an Attractive p-φ Interaction

This Letter presents the first experimental evidence of the attractive strong interaction between a proton and a ϕ meson. The result is obtained from two-particle correlations of combined p-ϕ⊕ p¯-ϕ pairs measured in high-multiplicity pp collisions at s√=13  TeV by the ALICE Collaboration. The spin-averaged scattering length and effective range of the p-ϕ interaction are extracted from the fully corrected correlation function employing the Lednický-Lyuboshits approach. In particular, the imaginary part of the scattering length vanishes within uncertainties, indicating that inelastic processes do not play a prominent role for the p-ϕ interaction. These data demonstrate that the interaction is dominated by elastic p-ϕ scattering. Furthermore, an analysis employing phenomenological Gaussian- and Yukawa-type potentials is conducted. Under the assumption of the latter, the N-ϕ coupling constant is found to be gN-ϕ=0.14±0.03(stat)±0.02(syst). This work provides valuable experimental input to accomplish a self-consistent description of the N-ϕ interaction, which is particularly relevant for the more fundamental studies on partial restoration of chiral symmetry in nuclear medium.publishedVersio

Una estrategia unificada para la síntesis enantioselectiva de los alcaloides del grupo de las madangaminas

[spa] El presente trabajo se centra en los alcaloides del grupo de las madangaminas, un pequeño grupo de alcaloides diaminopentacíclicos, aislados de esponjas marinas pertenecientes al orden Haplosclerida y derivados biogenéticamente de precursores con estructura de 3-alquilpiperidina. Estructuralmente, las madangaminas se caracterizan por la presencia de un núcleo diazatricílico (anillos ABC), sin precedentes entre los productos naturales, y dos puentes de carbono lineales que conectan el nitrógeno N-7 al carbono de la posición C-9 (anillo D) y el nitrógeno N-1 al carbono de la posición C-3 (anillo E). El anillo macrocíclico D varía en cada madangamina, tanto en tamaño (de 13 a 15 miembros) como en posición y grado de insaturación, mientras que el anillo E es idéntico en las madangaminas A-E (dos insaturaciones y 11 miembros) pero es diferente en la madangamina F (cuatro insaturaciones; 13 miembros). Además, la madangamina F incorpora una función hidroxilo en la posición C-4. Tras alcanzar la primera síntesis total de un alcaloide del grupo de las madangaminas, llevada a cabo por nuestro grupo en el 2014,1 en la presente Tesis Doctoral nos propusimos abordar la síntesis de otros alcaloides de esta familia. Para ello, centramos nuestra atención en las madangaminas A, B, C y E, para las que, al inicio de la presente Tesis Doctoral, no se había descrito ninguna síntesis total. Nuestra estrategia sintética se basa en la construcción enantioselectiva de un núcleo diazatricíclico altamente funcionalizado a partir de una lactama quiral derivada del R- fenilglicinol y en la posterior formación de los macrociclos D y E. La síntesis del sistema tricíclico 16 se ha logrado de forma satisfactoria y a gran escala (multigramos) mediante una secuencia sintética de 13 etapas con un rendimiento global del 15% a partir de la lactama derivada del feniglicinol 1a. A partir de este intermedio se ha estudiado la construcción del sistema ABCE común a las madangaminas A-E. En concreto, la estrategia basada en una reacción de Wittig con el iluro derivado de la sal de fosfonio 47 con posterior macrolactamización ha mostrado ser la más eficiente para la construcción del anillo macrocíclico E común a todas las madangaminas. De esta manera se ha sintetizado el tetraciclo ABCE de forma satisfactoria. Por otro lado, también a partir del compuesto tricíclico 16 se ha explorado la construcción de los macrociclos D de las madangaminas A, B, C y E. Un proceso de ring closing metathesis altamente eficiente (90% de rendimiento) ha permitido la construcción del anillo D de la madangamina C de trece miembros, aunque como mezcla inseparable de isómeros. Por hidrogenación del anterior se ha podido acceder al sistema tetracíclico ABCD de la madangamina E. Por otra parte, una estrategia basada en una reacción de coupling entre un alquino terminal y un ioduro diinico y posterior reducción del triple enlace resultante a trans- alqueno ha permitido por primera vez alcanzar la construcción del complejo macrociclo D de la madangamina B en una piperidina modelo. Finalmente, se ha descrito una nueva aproximación enantioselectiva a la síntesis de la madangamina A. La síntesis del sistema pentacíclico 111 representa la síntesis formal del alcaloide.[eng] Madangamines alkaloids constitute a small group of complex pentacyclic alkaloids isolated from marine sponges of the order Haposclerida. Structurally, these alkaloids have an unprecedented skeletal type, characterized by a diazatricyclic core (ABC rings) and two linear carbon bridges. The peripheral macrocyclic ring D is different in each madangamine, in size as well as in degree and position of unsaturation, whereas ring E is identical in madangamines A-E. In the context of our studies on the enantioselective synthesis of complex piperidine-containing natural products from phenylglycinol- derived bicyclic lactams, we have developed a unified strategy to access the variety of alkaloids of this group. Appling this strategy, that involves the formation of the macrocyclic rings after the construction of the highly functionalized central core, recently in our group was carried out the enantioselective synthesis of madangamine D, which represents the first total synthesis of an alkaloid of the madangamine group.1 In this Doctoral Thesis we focused our attention in the total synthesis of other members of the family: madangamines A, B, C and E. Starting from tricyclic intermediate 16, which was prepared by 13 steps, we performed the construction of the complex E ring, common to madangamines A-E. The construction of the different D rings was explored in model compounds as well in the tricyclic and tetracyclic intermediates; these studies allowed to accomplish the synthesis of the ring of madangamine B in a piperidine derivative, the ABCD system of madangamines C and E and the pentacyclic system of madangamine A, which represent the formal synthesis of this alkaloid