A Complex Stereochemical Relay Approach To The Antimalarial Alkaloid Ocimicide A1. Evidence For A Structural Revision

Ocimicide A1 (1) and the semisynthetic derivative ocimicide A2 (2) are highly potent antimalarial agents efficacious against chloroquine-sensitive and -resistant Plasmodium falciparum strains with IC50 values in the nanomolar and picomolar range, respectively. Members of this family have demonstrated radical cure in rhesus monkeys, without detectable toxicity, but their structure–function relationships and mechanism of action are unknown. Herein we describe a twelve-step synthesis of an advanced N-acylated pentacyclic precursor to the proposed structure of 1 (11% overall yield). Instability and poor P. falciparum growth inhibition of the corresponding free donor–acceptor cyclopropylamine, and large discrepancies between reported and both experimental and DFT-calculated 13C chemical shifts and coupling constants, suggest that substantial revision of the proposed structures may be necessary

Applications and usage of the real-time Neutron Monitor Database

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Applications and usage of the real-time Neutron Monitor Database

A high-time resolution Neutron Monitor Database (NMDB) has started to be realized in the frame of the Seventh Framework Programme of the European Commission. This database will include cosmic ray data from at least 18 neutron monitors distributed around the world and operated in real-time. The implementation of the NMDB will provide the opportunity for several research applications most of which will be realized in real-time mode. An important one will be the establishment of an Alert signal when dangerous solar cosmic ray particles are heading to the Earth, resulting into ground level enhancements effects registered by neutron monitors. Furthermore, on the basis of these events analysis, the mapping of all ground level enhancement features in near real-time mode will provide an overall picture of these phenomena and will be used as an input for the calculation of the ionization of the atmosphere. The latter will be useful together with other contributions to radiation dose calculations within the atmosphere at several altitudes and will reveal the absorbed doses during flights. Moreover, special algorithms for anisotropy and pitch angle distribution of solar cosmic rays, which have been developed over the years, will also be set online offering the advantage to give information about the conditions of the interplanetary space. All of the applications will serve the needs of the modern world which relies at space environment and will use the extensive network of neutron monitors as a multi-directional spectrographic detector. On top of which, the decreases of the cosmic ray intensity - known as Forbush decreases - will also be analyzed and a number of important parameters such as galactic cosmic ray anisotropy will be made available to the users of NMDB. A part of the NMDB project is also dedicated to the creation of a public outreach website with the scope to inform about cosmic rays and their possible effects on humans, technological systems and space-terrestrial environment. Therefore, NMDB will also stand as an informative gate on space research through neutron monitor's data usage. © 2010 Published by Elsevier Ltd. on behalf of COSPAR