Isolation, Structure Elucidation, Biosynthesis, and Synthesis of Antalid, a Secondary Metabolite from Polyangium species.

The isolation, structure elucidation, and synthesis of antalid (1), a novel secondary metabolite from Polyangium sp., is described herein. The structure elucidation of 1 was performed with the aid of mass spectrometry, high field NMR experiments, and crystal structure analysis. The absolute configuration of antalid was confirmed through the Mosher ester method and ultimately by total synthesis. In addition, the biosynthetic origin of this hybrid PKS-NRPS natural product was unraveled by the in silico analysis of its biosynthetic gene cluster.

Paleo-soraphens: chemical total syntheses and biological studies.

The soraphens are natural products that exhibit a molecular structure different from what would have been expected by following its polyketidal assembly line. The most significant differences are the presence of a hemiketal instead of a trisubstituted double bond and a double bond at C9 and C10 where a saturated carbon chain was expected. We were interested in the biological activity of the soraphens with architectures as described by the polyketide synthase since we hypothesized that these modifications reflect the evolutionary optimization of the soraphens. Herein we describe four additional derivatives of the so-called paleo-soraphens and their biological profiling to provide a picture of the hypothetical evolutionary optimization of this family of natural products. The syntheses required a unified and convergent strategy and their biological profiling was performed with the aid of impedance measurements. The results of these biological experiments are consistent with the proposed evolutionary optimization of the soraphens.

Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.

The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.

Readily accessible chiral diene ligands for Rh-catalyzed enantioselective conjugate additions of boronic acids.

Enabled by the broad scope of the Pd-catalyzed asymmetric alkylation of meso- and d,l-divinylethylene carbonate, several chiral diene ligands were prepared in two steps from commercial materials. Subsequently, these ligands were evaluated in the Rh-catalyzed asymmetric conjugate addition of boronic acids to enones.