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Physicochemical properties constitute a key factor for the success of a drug candidate. Whereas many strategies to improve the physicochemical properties of small heterocycle-type leads exist, complex hydrocarbon skeletons are more challenging to derivatize because of the absence of functional groups. A variety of C-H oxidation methods have been explored on the betulin skeleton to improve the solubility of this very bioactive, yet poorly water-soluble, natural product. Capitalizing on the innate reactivity of the molecule, as well as the few molecular handles present on the core, allowed oxidations at different positions across the pentacyclic structure. Enzymatic oxidations afforded several orthogonal oxidations to chemical methods. Solubility measurements showed an enhancement for many of the synthesized compounds.

Flavoproteins catalyse a diversity of fundamental redox reactions and are one of the most studied enzyme families (12). As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate (1,3,4). Here we report that the bacterial flavoenzyme EncM (5,6) catalyses the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics and isotope labelling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unexpected stable flavin-oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization., The antibiotic enterocin (Fig. 1, compound 1) is producedby various streptomycete bacteria (7) and contains a unique tricyclic caged core. Nearly 40 years ago, isotope labelling studies suggested the involvement [...]

Olefin metathesis has tremendously impacted all fields of synthetic chemistry. However, the control of the olefin stereochemistry during this process remains a grand challenge. Recent innovations in catalyst design have permitted control of the stereochemistry of the olefin product. Here, we discuss the development of stereoretentive olefin metathesis, with an emphasis on the synthesis of stereodefined polyalkenamers through ring-opening metathesis polymerization (ROMP). We then present our application of this unique reaction manifold to the preparation of all- cis poly(p -phenylene vinylene)s (PPVs). A dithiolate Ru catalyst was found to deliver perfect cis selectivity for the polymerization of a paracyclophane diene monomer. By using optimized conditions, all- cis PPVs with narrow dispersities and predictable molar masses were obtained by varying the ratio of monomer to catalyst. The high chain fidelity of the stereoretentive ROMP with a paracyclophane diene monomer enabled the preparation of well-defined diblock copolymers with a norbornene co-monomer. Photochemical isomerization of all- cis to all- trans PPVs was effected with both homopolymers and diblock copolymers. This process was shown to be selective for the PPV block, and resulted in changes in optical properties, polymer size, and solubility. Stereoretentive ROMP provides a promising platform for synthesizing polymers with unique properties, including photoresponsive all- cis PPVs with living characteristics. 1 Introduction 2 Synthetic Applications of Stereoretentive Olefin Metathesis 3 Stereocontrol of Polyalkenamers through Stereoretentive ROMP 4 Stereoretentive ROMP To Access All- cis Poly(p -phenylene vinylene)s 5 Conclusion [ABSTRACT FROM AUTHOR]

C-H Amination of unactivated sp3 centers (non-benzylic and non-allylic) using MeCN as an inexpensive source of nitrogen proceeds under scalable and mild conditions and high functional group tolerance in the presence of a modified Selectfluor reagent. [ABSTRACT FROM AUTHOR]

The cis / trans stereochemistry of repeating alkenes in polymers provides a powerful handle to modulate the thermal and mechanical properties of these soft materials, but synthetic methods to precisely dictate this parameter remain scarce. We report herein a cis -selective acyclic diene metathesis (ADMET) polymerization of readily available α,ω-diene monomers with high functional group tolerance. Identification of a highly stereoselective cyclometalated Ru catalyst allowed the synthesis of a broad array of polymers with cis contents up to 99%. This platform was leveraged to study the impact of the cis geometry on the thermal and mechanical properties of polyalkenamers, including an ABA triblock copolymer synthesized via extension of a cis -rich telechelic polyoctenamer with d,l-lactide. These results suggest that cis -selective ADMET affords an efficient strategy to tune the properties of a variety of polymers.

Poly( p -phenylenevinylene)s (PPVs), a staple of the conductive polymer family, consist of alternating alkene and phenyl groups in conjugation. The physical properties of this organic material are intimately linked to the cis / trans configuration of the alkene groups. While many synthetic methods afford PPVs with all- trans stereochemistry, very few deliver the all- cis congeners. We report herein a synthesis of all- cis PPVs with living characteristics via stereoretentive ring-opening metathesis polymerization (ROMP). Exquisite catalyst control allows for the preparation of homopolymers or diblock copolymers with perfect stereoselectivity, narrow dispersities, and predictable average molar masses. All- cis PPVs can then serve as light-responsive polymers through clean photoisomerization of the stilbenoid units.

During the last 40 years, researchers investigating photoinitiated cationic polymerizations have delivered tremendous success in both industrial and academic settings. A myriad of photoinitiating systems have been developed, thus allowing polymerization of a broad array of monomers (e.g., epoxides, vinyl ethers, alkenes, cyclic ethers, and lactones) under practical, inexpensive, and environmentally benign conditions. More recently, owing to progress in photoredox catalysis, photocontrolled cationic polymerization has emerged as a means to precisely regulate polymer chain growth. This Minireview provides a concise historical perspective on cationic polymerization induced by light and discusses the latest advances in both photoinitiated and photocontrolled processes. The latter are exciting new directions for the field that will likely impact industries ranging from micropatterning to the synthesis of complex biomaterials and sequence-controlled polymers., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Physicochemical properties constitute a key factor for the success of a drug candidate. Whereas many strategies to improve the physicochemical properties of small heterocycle-type leads exist, complex hydrocarbon skeletons are more challenging to derivatize because of the absence of functional groups. A variety of C-H oxidation methods have been explored on the betulin skeleton to improve the solubility of this very bioactive, yet poorly water-soluble, natural product. Capitalizing on the innate reactivity of the molecule, as well as the few molecular handles present on the core, allowed oxidations at different positions across the pentacyclic structure. Enzymatic oxidations afforded several orthogonal oxidations to chemical methods. Solubility measurements showed an enhancement for many of the synthesized compounds., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)