https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Oxysterols are a class of endogenous signaling molecules that can activate the Hedgehog pathway, which has critical roles in development, regeneration and cancer. However, it has been unclear how oxysterols influence Hedgehog signaling, including whether their effects are mediated through a protein target or indirectly through effects on membrane properties. To answer this question, we synthesized the enantiomer and an epimer of the most potent oxysterol, 20(S)-hydroxycholesterol. Using these molecules, we show that the effects of oxysterols on Hedgehog signaling are exquisitely stereoselective, consistent with the hypothesis that they function through a specific protein target. We present several lines of evidence that this protein target is the seven-pass transmembrane protein Smoothened, a major drug target in oncology. Our work suggests that these enigmatic sterols, which have multiple effects on cell physiology, may act as ligands for signaling receptors and provides a generally applicable framework for probing sterol signaling mechanisms.

/pdf/oxysterols-are-allosteric-activators-of-the-oncoprotein-3v3yiobr7b.pdf

Oxysterols are allosteric activators of the oncoprotein Smoothened

A mild and operationally simple iron-catalyzed protocol for the selective aerobic oxidation of aromatic olefins to carbonyl compounds is described. Catalyzed by a Fe(III) species bearing a pyridine bisimidazoline ligand at 1 atm of O2, α- and β-substituted styrenes were cleaved to afford benzaldehydes and aromatic ketones generally in high yields with excellent chemoselectivity and very good functional group tolerance, including those containing radical-sensitive groups. With α-halo-substituted styrenes, the oxidation took place with concomitant halide migration to afford α-halo acetophenones. Various observations have been made, pointing to a mechanism in which both molecular oxygen and the olefinic substrate coordinate to the iron center, leading to the formation of a dioxetane intermediate, which collapses to give the carbonyl product.

Green and Efficient: Iron-Catalyzed Selective Oxidation of Olefins to Carbonyls with O2.

Enantiospecific, Biosynthetically Inspired Formal Total Synthesis of (+)-Liphagal

https://pubs.rsc.org/en/content/articlepdf/2016/np/c6np00059b

Diterpenoids of terrestrial origin

Further Synthetic Studies Towards the Austrodorane Skeleton: Synthesis of Austrodoral

Studies towards the synthesis of cheilanthane sesterterpenoids: superacidic cyclisation of methyl 13Z,17Z- and 13Z,17E-bicyclogeranylfarnesoates

Synthesis of a functionalized furan via ozonolysis—further confirmation of the Criegee mechanism

The family of scalaranic sesterterpenoids has been known since the early 70s, but they have attracted the attention of synthetic organic chemists only in the last decade. These marine natural products are considered secondary metabolites of marine organisms and have shown promising biological properties. Synthetic approaches towards scalaranes are discussed in the present review. Scalaranes are quite complex compounds, with many chiral centers and their transformations are strongly directed by steric effects of different functional groups attached to the tetracyclic framework. Therefore, methods of assembling the scalaranic skeleton are examined first, followed by the synthesis of natural products or their analogues on the basis of the available tetracyclic template.

Veaceslav Kulciţki

Papers

Further Synthetic Studies Towards the Austrodorane Skeleton: Synthesis of Austrodoral

Studies towards the synthesis of cheilanthane sesterterpenoids: superacidic cyclisation of methyl 13Z,17Z- and 13Z,17E-bicyclogeranylfarnesoates

Synthesis of a functionalized furan via ozonolysis—further confirmation of the Criegee mechanism

Synthetic paths towards scalaranes: Assembling the scalaranic skeleton and further transformations

Occurrence, biological activity and synthesis of cheilanthane sesterterpenoids