Probing the SAR of dEpoB via chemical synthesis: a total synthesis evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B

A practical total synthesis of 26-(1,3-dioxolanyl)-12,13-desoxyepothilone B (26-dioxolanyl dEpoB) was accomplished in a highly convergent manner. A novel sequence was developed to produce the vinyl iodide segment 17 in high enantiomeric excess, which was used in a key B-alkyl Suzuki merger. Subsequently, a Yamaguchi macrocyclization formed the core lactone, while a selective oxidation and a late stage Noyori acetalization incorporated the dioxolane functionality. Sufficient amounts of synthetic 26-dioxolane dEpoB were produced using this sequence for an in vivo analysis in mice containing xenograft CCRF-CEM tumors.     

Synthesis of pyrrolo[3,4-c]pyridazines

We have prepared the pyrrolopyridazines 7a-f starting from the diazo compounds 4 . The synthesis involves a tandem condensation-aza-Wittig reaction or a combination of Wittig and aza-Wittig reactions as key steps. Reaction of pyridazine 7d with diazomethane results in C-methylation to yield 7g . Sodium borohydride reduces 7d to either the dihydropyridazine 12 or the hydroxylactam 13b depending of the reaction conditions.     

(Non)thermal aspects of charmonium production and a new look at J/ψ suppression

To investigate a recent proposal that J/ψ production in ultra-relativistic nuclear collisions is of thermal origin we have reanalyzed the data from the NA38/50 Collaboration within a thermal model including charm. Comparison of the calculated with measured yields demonstrates the non-thermal origin of hidden charm production at SPS energy. However, the ratio ψ′/(J/ψ) exhibits, in central nucleus-nucleus collisions, thermal features which lead us to a new interpretation of open charm and charmonium production at SPS energy. Implications for RHIC and LHC energy measurements will be discussed.     

Semihard scattering unraveled from collective dynamics by two-pion azimuthal correlations in 158A GeV/c Pb+Au collisions

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-p(T) pions (p(T)>1 GeV/c) have been measured close to midrapidity in 158A GeV/c Pb+Au collisions by the CERES experiment. Elliptic flow (v(2)) rises linearly with p(T) to a value of about 10% at 2 GeV/c. Beyond p(T) approximately 1.5 GeV/c, the slope decreases considerably, possibly indicating a saturation of v(2) at high p(T). Two-pion azimuthal anisotropies for p(T)>1.2 GeV/c exceed the elliptic flow values by about 60% in midcentral collisions. These nonflow contributions are attributed to nearside and back-to-back jetlike correlations, the latter exhibiting centrality dependent broadening.     

A Monte Carlo model for ‘jet quenching’

We have developed the Monte Carlo simulation program Jewel 1.0 (Jet Evolution With Energy Loss), which interfaces a perturbative final-state parton shower with medium effects occurring in ultra-relativistic heavy-ion collisions. This is done by comparing for each jet fragment the probability of further perturbative splitting with the density-dependent probability of scattering with the medium. A simple hadronisation mechanism is included. In the absence of medium effects, we validate Jewel against a set of benchmark jet measurements. For elastic interactions with the medium, we characterise not only the medium-induced modification of the jet, but also the jet-induced modification of the medium. Our main physical result is the observation that collisional and radiative medium modifications lead to characteristic differences in the jet fragmentation pattern, which persist above a soft background cut. We argue that this should allow one to disentangle collisional and radiative parton energy loss mechanisms by measuring the n-jet fraction or a class of jet shape observables.