Tufan K. Mukhopadhyay

Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4 + 2] (Diels-Alder) cycloaddition, which efficiently furnishes cyclohexene derivatives. In comparison, the [6 + 4] cycloaddition, which forms cyclodecatriene derivatives from triene and diene reactants, is far less common. Here, we report a short and stereoselective synthesis of a highly unsaturated macrolactone that has been proposed as a biosynthetic precursor of the tricyclic cyclodecatriene collinoketone A and the neuroprotective natural product collinolactone. We find that this macrolactone undergoes effective transannular [6 + 4] cycloadditions to afford stereoisomers of collinoketone A, which we name collinoketones B and C. Our work reassigns the structure of the natural product reported as collinoketone A and highlights the complexity of [6 + 4] cycloadditions with conformationally flexible substrates.

Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4+2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene derivatives. In comparison, the [6+4] cycloaddition, which forms cyclodecatriene derivatives from triene and diene reactants, is far less common. Here, we report a short and stereoselective synthesis of a highly unsaturated macrolactone that has been proposed as a biosynthetic precursor of the tricyclic cyclodecatriene collinoketone A and the neuroprotective natural product collinolactone. We find that this macrolactone undergoes effective transannular [6+4] cycloaddi-tions to afford stereoisomers of collinoketone A, which we name collinoketones B and C. Our work reassigns the structure of the natural product reported as collinoketone A and highlights the complexity of [6+4] cycloadditions with conformationally flexible substrates.

Activation of the oxysterol‐sensing transcription factor liver X receptor (LXR) has been studied as a therapeutic strategy in metabolic diseases and cancer but is compromised by the side effects of LXR agonists. Local LXR activation in cancer treatment may offer an opportunity to overcome this issue suggesting potential uses of photopharmacology. We report the computer‐aided development of photoswitchable LXR agonists based on the T0901317 scaffold, which is a known LXR agonist. Azologization and structure‐guided structure‐activity relationship evaluation enabled the design of an LXR agonist, which activated LXR with low micromolar potency in its light‐induced (Z)‐state and was inactive as (E)‐isomer. This tool sensitized human lung cancer cells to chemotherapeutic treatment in a light‐dependent manner supporting potential of locally activated LXR agonists as adjuvant cancer treatment.

Glycerophospholipids are major components of cellular membranes and provide important signaling molecules. Besides shaping membrane properties, some bind to specific receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening of a phosphate triester epoxide with carboxylic acids catalyzed by Jacobsen's Co(salen) complex. We show that this method can be applied to a variety of commercially available fatty acids, photoswitchable fatty acids, and other carboxylic acids to provide the corresponding glycerophosphate derivatives.

Article published online: 15 June 2022 © 2022. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article published online: 15 June 2022 © 2022. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Publication Date: 17 May 2022 (online) © 2022. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

C–H arylation of arenes without the use of directing groups is a challenge, even for simple molecules, such as benzene. We describe spatial anion control as a concept for the design of catalytic sites for C–H bond activation, thereby enabling nondirected C–H arylation of arenes at ambient temperature. The mild conditions enable late-stage structural diversification of biologically relevant small molecules, and site-selectivity complementary to that obtained with other methods of arene functionalization can be achieved. These results reveal the potential of spatial anion control in transition-metal catalysis for the functionalization of C–H bonds under mild conditions.

The dimeric β-diketiminate manganese hydride compound, [(^2,6-iPr2PhBDI)Mn(μ-H)]₂, was prepared by treating [(^2,6-iPr2PhBDI)Mn(μ-Cl)]₂ with NaEt₃BH. This compound was characterized by single crystal X-ray diffraction and found to feature high-spin Mn centres that exhibit strong magnetic coupling by EPR spectroscopy. Once characterized, [(^2,6-iPr2PhBDI)Mn(μ-H)]₂ was found to mediate the hydrosilylation of a broad scope of alkenes at elevated temperature. Aliphatic alkenes were found to undergo anti-Markovnikov hydrosilylation, while the hydrosilylation of styrenes using [(^2,6-iPr2PhBDI)Mn(μ-H)]₂ afforded Markovnikov's product. Importantly, this catalyst has also been employed for the cross-linking of industrially-relevant silicones derived from vinyl-terminated poly(dimethylsiloxane) and 1,2,4-trivinylcyclohexane with catalyst loadings as low as 0.05 mol%. To gain a mechanistic understanding of [(^2,6-iPr2PhBDI)Mn(μ-H)]₂-catalyzed olefin hydrosilylation, 4-tert-butylstyrene was added to [(^2,6-iPr2PhBDI)Mn(μ-H)]₂ and conversion to the monomeric Mn alkyl complex, (^2,6-iPr2PhBDI)Mn(CH(CH₃)(4-^tBuPh)), was observed. Isolation of this secondary alkyl intermediate confirms that olefin insertion into the Mn–H bond dictates the observed regioselectivities. The importance of our mechanistic findings as they relate to recent advances in Mn hydrosilylation catalysis is described herein.