Photomediated ring contraction of saturated heterocycles

Jurczyk, Justin; Lux, Michaelyn C.; Adpressa, Donovon A.; Kim, Sojung F.; Lam, Yu-hong; Yeung, Charles S.; Sarpong, Richmond

doi:10.1126/science.abi7183

Cited by 82 publications

(77 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1A). In contrast, complementary approaches that can directly modify the underlying core skeleton of a molecule are less common, despite their potential to expand the accessible chemical space (4)(5)(6)(7)(8)(9)(10)(11). Formal single atom insertion reactions to modify aromatic moieties have proven to be especially challenging given the inherent inertness of aromatic carbon-based skeleton towards cleavage of a carbon-carbon bond (12).…”

Section: Main Textmentioning

confidence: 99%

Late-stage diversification of indole skeletons through nitrogen atom insertion

Reisenbauer

Green

Franchino

et al. 2022

Preprint

View full text Add to dashboard Cite

Advances in the field of late-stage functionalization have expedited lead-structure discovery and established new opportunities to access valuable molecules. Although many peripheral late-stage transformations, mainly focusing on C–H functionalizations, have been reported, reliable strategies to directly edit the core skeleton of lead compounds have remained scarce. Late-stage remodeling strategies of widely encountered and pharmaceutically relevant scaffolds, such as indoles, would offer enormous potential to expand accessible chemical space. Herein, we report the skeletal editing of indoles through nitrogen atom insertion, accessing their corresponding quinazoline or quinoxaline bioisosteres via trapping of an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This unique reactivity is unlocked through the strategic use of a silyl group which acts as a reactivity-controlling element to suppress the inherent nucleophilicity of the nitrogen in indoles. Importantly, the utility of this highly functional group-tolerant methodology in the context of late-stage skeletal editing of several commercial drugs is demonstrated.

show abstract

Section: Main Textmentioning

confidence: 99%

Late-stage diversification of indole skeletons through nitrogen atom insertion

Reisenbauer

Green

Franchino

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…There are other examples of success with violet and blue light in microbe inactivation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Even other examples are emerging with violet-blue or blue light in synthetic organic (22)(23)(24)(25)(26)(27)(28) and photopolymerization reactions (29), and naturally, there is a history of blue light therapy in neonatal jaundice (30)(31)(32)(33). Yet, following Maclean and coworker's first accomplishment of microbe reduction to decent levels is the secondary challenge of protecting the sample against protein photooxidation (34)(35)(36)(37).…”

Section: Maximal Violet-blue Disinfectionmentioning

confidence: 99%

Violet‐blue Light Induces “Natural” Photodynamic Plasma Disinfection with Endogenous Sensitizers

Greer

2022

Photochem & Photobiology

View full text Add to dashboard Cite

Naturally, endogenous porphyrins can provide sensitized disinfection power, and to photobiologists' delight, violet-blue light has potential virtues, but progress is needed before violet-blue light treatment can be used for microbe treatment of blood plasma, and yet safeguard against protein photooxidation. A report by Maclean et al. in this issue of Photochemistry & Photobiology on microbe reduction in blood plasma showing negligible competing protein photooxidation may bring that goal a step closer.

show abstract

“…1 Recent reports in this area have included nitrogen deletion, 2 single-atom insertion, 3 and ring contractions. 4 Through a collaboration involving researchers at the University of California-Berkeley in Prof. Richmond Sarpong's laboratory and at the research labs of Merck & Co., Inc., Kenilworth, NJ, USA -known as MSD outside of the US and Canada -a light-mediated ring contraction of saturated six-membered heterocycles to five-membered rings that relocates the heteroatom from an endocyclic to exocyclic position has been achieved. This academia/industry partnership started as part of the "Disruptive Chemistry" initiative at MSD -an effort focused on developing enabling chemical reactions of importance for industrial applications, including novel scaffold changes to precisely edit molecules.…”

Section: Literature Coverage Synformmentioning

confidence: 99%

Synform Issue 2022/1

Zanda¹

2021

Synthesis

View full text Add to dashboard Cite

I am delighted to introduce a new year of SYNFORM with an absolutely first-class January issue, packed full of great science, published in top-notch journals. If a good beginning bodes well, it is safe to say that we have a very exciting year ahead. The critical duty of kicking off this season is on the shoulders of Y. Nagata (Japan) who is the protagonist -and past Thieme Chem istry Journals Awardee -of our Young Career Focus interview, which zooms in on robot-assisted synthesis and stereochemical properties of polymers in solution. The first Literature Coverage article covers a recent ground-breaking publication in Science by the group of R. Sarpong (USA) on a photo-mediated ring contraction of saturated heterocycles, such as piperid ines, cyclic ethers and thioethers, which allows for the skeletal editing of complex cyclic organic molecules. The next Literature Coverage article covers another recent Science paper, authored by the group of W. Han (P. R. of China), on a conceptually new approach to the notoriously challenging selective oxidation of phenols, which has been achieved via iron-catalysed non-directed arene C-H hydroxylation, enabled by L-cystinederived ligands inspired by cytochrome P450 enzymes. The fourth and final article of this pyrotechnic issue covers a new approach -developed through a collaboration involving the groups of M. Bradley (UK) and J. Geng (P. R. of China), and published in Nat. Chem.for activating prodrugs using radiotherapy, and specifically X-rays, which holds great promise for future clinical applications.

show abstract

Photomediated ring contraction of saturated heterocycles

Cited by 82 publications

References 64 publications

Late-stage diversification of indole skeletons through nitrogen atom insertion

Late-stage diversification of indole skeletons through nitrogen atom insertion

Violet‐blue Light Induces “Natural” Photodynamic Plasma Disinfection with Endogenous Sensitizers

Synform Issue 2022/1

Contact Info

Product

Resources

About