Bisindole Alkaloids from the Alstonia Species: Recent Isolation,Bioactivity, Biosynthesis,and Synthesis

Bisindoles are structurally complex dimers and are intriguing targets for partial and total synthesis. They exhibit stronger biological activity than their corresponding monomeric units. Alkaloids, including those containing C-19 methyl-substitution in their monomeric units, their synthetic derivatives, and their mismatched pairs can be attractive targets for synthesis and may unlock better drug targets. We herein discuss the isolation of bisindoles from various Alstonia species, their bioactivity, putative biosynthesis, and synthesis. The total synthesis of macralstonidine, macralstonine, O-acetylmacralstonine, and dispegatrine, as well as the partial synthesis of alstonisidine, villalstonine, and macrocarpamine are also discussed in this review. The completion of the total synthesis of pleiocarpamine by Sato et al. completes the formal synthesis of the latter two bisindoles.     

Segmented Frequency-domain Fluorescence Lifetime Measurements: Minimizing the Effects of Photobleaching Within a Multi-component System

This study introduces a newly developed frequency segmentation and recombination method for frequency-domain fluorescence lifetime measurements to address the effects of changing fractional contributions over time and minimize the effects of photobleaching within multi-component systems. Frequency segmentation and recombination experiments were evaluated using a two component system consisting of fluorescein and rhodamine B. Comparison of experimental data collected in traditional and segmented fashion with simulated data, generated using different changing fractional contributions, demonstrated the validity of the technique. Frequency segmentation and recombination was also applied to a more complex system consisting of pyrene with Suwannee River fulvic acid reference and was shown to improve recovered lifetimes and fractional intensity contributions. It was observed that photobleaching in both systems led to errors in recovered lifetimes which can complicate the interpretation of lifetime results. Results showed clear evidence that the frequency segmentation and recombination method reduced errors resulting from a changing fractional contribution in a multi-component system, and allowed photobleaching issues to be addressed by commercially available instrumentation. Electronic supplementary material The online version of this article doi: contains supplementary material, which is available to authorized users.     

Sensitivity of a continuum vocal fold model to geometric parameters, constraints, and boundary conditions

The influence of key dimensional parameters, motion constraints, and boundary conditions on the modal properties of an idealized, continuum model of the vocal folds was investigated. The Ritz method and the finite element method were used for the analysis. The model's vibratory modes were determined to be most sensitive to changes in the anterior-posterior length of the vocal fold model, due to the influence of three-dimensional stress components acting in the transverse plane. Anterior/ posterior boundary conditions were found to have a significant influence on the vibratory response. Overestimation of modal frequencies resulted when vibration of the structure was restricted to the transverse plane. The overestimation of each modal frequency was proportional to the ratio of longitudinal to transverse Young's modulus, and was significant for ratio values less than 20.     

First enantiospecific total synthesis of the important biogenetic intermediates, (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epi-vellosimine and macusine A

The first enantiospecific total synthesis of the alkaloids 16-epi-vellosimine (1), (+)-polyneuridine (2), (+)-polyneuridine aldehyde (3), and macusine A (4) is reported. The key oxidation was accomplished with the Corey-Kim reagent to provide the important biogenetic intermediates, 16-epi-vellosimine (1) and polyneuridine aldehyde (3), the latter of which is required for the conversion of the sarpagan skeleton into the ajmalan system in the biosynthesis of quebrachidine. [reaction: see text].