Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium.

Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of 13C chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations.

Stereochemical Revision, Total Synthesis, and Solution State Conformation of the Complex Chlorosulfolipid Mytilipin B.

Chlorosulfolipids constitute a structurally intriguing and synthetically challenging class of marine natural products that are isolated from mussels and freshwater algae. The most complex structure from this family of compounds is currently represented by Mytilipin B, isolated in 2002 from culinary mussel Mytilus galloprovincialis, whose initially proposed structure was shown to be incorrect. In this study, we present the synthesis of four diastereomers which allowed the reassignment of eight stereocenters and the stereochemical revision of Mytilipin B, along with the determination of the dominant solution-state conformation.

Enantioselective Chemo- and Biocatalysis: Partners in Retrosynthesis.

Recent developments of stereoselective biocatalytic and chemocatalytic methods are discussed. The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focused attention on retrosynthetic considerations and analysis. The transformations presented are organized according to bond disconnections and attendant synthetic methods. The review is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches. It depicts for researchers in bio- and chemocatalysis a road map of challenges and opportunities for the evolution (and at times revolution) in chemical synthesis.