Synthetic applications of a three-component Mannich reaction. Total synthesis of IL-6 inhibitor (+)-madindoline A and B

A three-component Mannich reaction of 3a-hydroxyfuroindoline (3), β-ketoester and formaldehyde was employed as an efficient and concise method to synthesize naturally-occurring (+)-Madindolines A (1) and B (2). The scope and limitations of the Mannich reaction with 3 are described.     

Enzymatic assembly of the bis-indole core of rebeccamycin

Rebeccamycin is a member of the family of indolocarbazole antibiotics with broad spectrum antitumor activity. The indolocarbazole framework is derived from two molecules of tryptophan, but very little is known about the enzymes involved in rebeccamycin biosynthesis. Here, we show that RebD is responsible for all catalytic steps forming the central pyrrole ring of chlorochromopyrrolic acid from two molecules of chloroindolepyruvic acid. This transformation does not require any additional cofactors and constitutes the first step of bis-indole formation in the biosynthesis of rebeccamycin.     

Novel antifungal polyene amides from the myxobacterium Cystobacter fuscus: isolation, antifungal activity and absolute structure determination

Three new unstable metabolites, (6E,10Z)-2′-O-methylmyxalamide D (1), 2′-O-methylmyxalamide D (2) and (6E)-2′-O-methylmyxalamide D (3) were isolated from the myxobacterium Cystobacter fuscus. The planar structures were elucidated by spectroscopic analyses to be geometrical isomers of a polyene amide related to a myxobacterial metabolite, myxalamide D (4). Their absolute stereochemistry was determined by synthesis of degradation products. Antifungal activities of 1-3 as well as their acetates were evaluated against the phythopathogenic fungus Phythopthora capsici.     

Kinetics and mechanism of the base hydrolysis of cis-eq-[Cr(NCS)(S-pdtra)]−, trans-eq-[Cr(NCS)(edtrp)]− and trans-eq-[Cr(NCS)(R-pdtrp)]− complexes. Strong rate enhancement for NCS− ligand release with an increase of [OH−] only for the trans-equatorial isomers

The [Cr(NCS)(edtrp)]⁻, [Cr(NCS)(R-pdtrp)]⁻ and [Cr(NCS)(S-pdtra)]⁻ complexes, that are derivatives of the trans-equatorial isomers of [Cr(edtrp)(H₂O)]° and [Cr(R-pdtrp)(H₂O)]° and the cis-equatorial isomer of [Cr(S-pdtra)-(H₂O)]° (edtrp = ethylenediamine-N,N,N′-tripropionate, R-pdtrp = R-propane-1,2-diamine-N,N,N′-tripropionate, S-pdtra = S-propane-1,2-diamine-N,N,N′-triacetate) undergo aquation in alkaline media with a strong dependence of the rate on [OH⁻] for the trans-equatorial isomers and a very weak dependence for the cis-equatorial isomer. The thiocyanate ligand release follows a stereoretentive course for all reactants. Based on kinetic data the reaction mechanism has been discussed. Rate differences between the isomers are interpreted in terms of an interchange via a conjugate base (I c.b.) mechanism, assuming an equilibrium between the cis-equatorial-Cr^III-S-pdtra complexes with penta- and tetradentate coordination of the edta-like ligand. This revised version was published online in June 2006 with corrections to the Cover Date.     

Effects of substituent groups of polyimides on sorption and diffusion of gases

Sorption rate curves of CO₂, N₂, and He gases below 1 atm were measured for polyimide films prepared from benzophenone tetracarboxylic dianhydride (BTDA) with 3,5-diaminotoluene trifluoride (DATF), 2,4-diaminotoluene (DAT), m-phenylenediamine (MPD), and diaminobenzoic acid (DABA). The molecular structures of these four polyimides differ only in the substituent groups of the diamine structure. These polyimides exhibit dualmode type sorption isotherms for carbon dioxide that are concave to the pressure axis, typical of glassy polymer/gas system. The apparent diffusion coefficients below 1 atm pressure of carbon dioxide for this series of compounds decrease in the order: BTDA-DATF > BTDA-DAT > BTDA-MPD > BTDA-DABA. A linear relation between the logarithm of the apparent diffusion coefficient and the reciprocal of free volume, calculated by the method of Bondi using density data, is found for these polyimides. However, this tendency is not observed for the other two gases. The activation energies of the apparent diffusion coefficients at 20 cmHg pressure of carbon dioxide increase with increasing cohesive energy density of the polyimides. The energy per mole of free volume elements in a liquidlike structure in each cohesive energy density may be equated to the activation energy and used to calculate the free volume. The values from the activation energy are almost the same as those from Bondi's method.     

Sorption and diffusion of gases in a polyimide

Sorption and diffusion of gases (CO₂, N₂, and He) in a polyimide (PI2080) film were measured by using an apparatus which gives the sorption rate curves from the initial state to the equilibrium state. Nonlinear isotherms observed for CO₂ sorption were interpreted successfully in terms of the dual-mode model for sorption in glassy polymers. Linear isotherms observed for N₂ and He seemed to obey Henry's law. Two diffusion coefficients (D_I and D_E) were obtained using the short-time method and the long-time method for a Fickian diffusion model, together with the equilibrium solubility (C_e) from each experiment. The initial sorption rate curves agreed with the calculated curves using D_I, however near sorption equilibrium the curves are in accord with the calculated curves using D_E. These observations suggest that some relaxation process is superimposed on the diffusion process. The non-Fickian transport data were correlated successfully with a model that combines time-dependent diffusion and the Fickian model.     

Long-term evolution of stellar self-gravitating systems away from thermal equilibrium: connection with nonextensive statistics

With particular attention to the recently postulated introduction of a nonextensive generalization of Boltzmann-Gibbs statistics, we study the long-term stellar dynamical evolution of self-gravitating systems on time scales much longer than the two-body relaxation time. In a self-gravitating N-body system confined in an adiabatic wall, we show that the quasiequilibrium sequence arising from the Tsallis entropy, so-called stellar polytropes, plays an important role in characterizing the transient states away from the Boltzmann-Gibbs equilibrium state.