Synthetic and pharmacophoric studies of quinocarcin

1990 Fall.Includes bibliographical references.A new synthetic approach to the stereoselective total synthesis of the structurally unique antitumor antibiotic quinocarcin (1) is described. The utilization of model studies in this approach has led to novel methodologies concerning the construction of 1-(hydroxymethyl)-8-methoxy-1,2,3,4-tetrahydroisoquinolin-4-one (195) and several variably substituted pyrrolidines (180, 181, 182 and 183). These methodologies are discussed in terms of their synthetic utility as well as their mechanistic aspects. The synthetic approach to quinocarcin described herein allowed for the construction of several oxazolidine containing alkaloids which incorporate various aspects of the 8-11- iminoazepinotetrahydroiso-quinoline skeleton of quinocarcin. To this end the synthesis of a new tetracyclic oxazolidine moiety (240), which mimics quinocarcin's DNA nicking capabilities and represents the isolation of the pharmacophore of this novel antibiotic was achieved. The significance of the chemical stability and biological activity of 240 relative to quinocarcin is discussed

Radical overhaul needed to halt Earth's sixth great extinction event

Life has existed on Earth for roughly 3.7 billion years. During that time we know of five mass extinction events — dramatic episodes when many, if not most, life forms vanished in a geological heartbeat. The most recent of these was the global calamity that claimed the dinosaurs and myriad other species around 66 million years ago. Growing numbers of scientists have asserted that our planet might soon see a sixth massive extinction — one driven by the escalating impacts of humanity. Others, such as the Swedish economist Bjørn Lomborg, have characterised such claims as ill-informed fearmongering. We argue emphatically that the jury is in and the debate is over: Earth's sixth great extinction has arrived

Vertebrates on the Brink as Indicators of Biological Annihilation and the Sixth Mass Extinction

The ongoing sixth mass species extinction is the result of the destruction of component populations leading to eventual extirpation of entire species. Populations and species extinctions have severe implications for society through the degradation of ecosystem services. Here we assess the extinction crisis from a different perspective. We examine 29,400 species of terrestrial vertebrates, and determine which are on the brink of extinction because they have fewer than 1,000 individuals. There are 515 species on the brink (1.7% of the evaluated vertebrates). Around 94% of the populations of 77 mammal and bird species on the brink have been lost in the last century. Assuming all species on the brink have similar trends, more than 237,000 populations of those species have vanished since 1900. We conclude the human-caused sixth mass extinction is likely accelerating for several reasons. First, many of the species that have been driven to the brink will likely become extinct soon. Second, the distribution of those species highly coincides with hundreds of other endangered species, surviving in regions with high human impacts, suggesting ongoing regional biodiversity collapses. Third, close ecological interactions of species on the brink tend to move other species toward annihilation when they disappear—extinction breeds extinctions. Finally, human pressures on the biosphere are growing rapidly, and a recent example is the current coronavirus disease 2019 (Covid-19) pandemic, linked to wildlife trade. Our results reemphasize the extreme urgency of taking much-expanded worldwide actions to save wild species and humanity’s crucial life-support systems from this existential threat