Exploring and exploiting biologically relevant chemical space.

Small bioactive molecules are pre-requisite for any discovery discipline. Aware of the fact that bioactivity is not randomly dispersed in the vast chemical space, chemists have been developing hypothesis that can lead them to the islands of bioactivities. Natural products have always been a source of inspiration and their structural motifs provide biologically relevant starting points for library synthesis.

Silver catalyzed cascade synthesis of alkaloid ring systems: concise total synthesis of fascaplysin, homofascaplysin C and analogues.

A silver catalyzed and microwave assisted one-pot cascade synthesis provides efficient access to diverse alkaloid-inspired scaffold classes, and a concise and efficient total synthesis of homofascaplysin C and fascaplysin.

BINOL-derived phosphoramidites in asymmetric hydrogenation: can the presence of a functionality in the amino group influence the catalytic outcome?

In discovering the remarkable catalytic properties of BINOL-derived phosphoramidites (binoP-NR(2)), Dutch researchers recently achieved a long-awaited breakthrough in asymmetric catalysis. For the first time, easily accessible monodentate chiral P(III) ligands turned out to provide high enantioselectivities when used in rhodium-catalysed olefin hydrogenation. The simplest ligand representative of this family is MonoPhos, which can be made straightforwardly from BINOL and hexamethylphosphorous triamide.

Efficient asymmetric hydrogenation of olefins with hydrazine-derived diphosphoramidites.

Enantiopure, BINOL-derived diphosphoramidites built upon an achiral hydrazine spacer are efficient ligands for the hydrogenation of 2-(acetylamino)-3-(aryl)-propenoic methyl esters. The activity and enantioselectivity of the hydrazine derivatives were shown to be markedly influenced by the nature of the two NR substituents, symmetrical but bulky R groups leading to the best results. A diphosphosphoramidite obtained from (t)BuHNNH(t)Bu resulted in ee's as high as 95%.