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1. Interactions of Truncated Menaquinones in Lipid Monolayers and Bilayers

   https://doi.org/https://doi.org/10.3390/ ijms22189755  

   Van Cleave, C.; Koehn, J. T.; Pereira, C. S.; Haase, A. A.; Peters, B. J.; Croslow, S. W.; McLaughlin, K. G.; Werst, K. R.; Goach, A. L.; Crick, D. C.; et al (September 2021, International journal of molecular sciences)

   null (Ed.)

   Menaquinones (MK) are hydrophobic molecules that consist of a naphthoquinone headgroup and a repeating isoprenyl side chain and are cofactors used in bacterial electron transport systems to generate cellular energy. We have previously demonstrated that the folded conformation of truncated MK homologues, MK-1 and MK-2, in both solution and reverse micelle microemulsions depended on environment. There is little information on how MKs associate with phospholipids in a model membrane system and how MKs affect phospholipid organization. In this manuscript, we used a combination of Langmuir monolayer studies and molecular dynamics (MD) simulations to probe these questions on truncated MK homologues, MK-1 through MK-4 within a model membrane. We observed that truncated MKs reside farther away from the interfacial water than ubiquinones are are located closer to the phospholipid tails. We also observed that phospholipid packing does not change at physiological pressure in the presence of truncated MKs, though a difference in phospholipid packing has been observed in the presence of ubiquinones. We found through MD simulations that for truncated MKs, the folded conformation varied, but MKs location and association with the bilayer remained unchanged at physiological conditions regardless of side chain length. Combined, this manuscript provides fundamental information, both experimental and computational, on the location, association, and conformation of truncated MK homologues in model membrane environments relevant to bacterial energy production. 

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2. A One‐Pot Biocatalytic Cascade to Access Diverse l ‐Phenylalanine Derivatives from Aldehydes or Carboxylic Acids

   https://doi.org/10.1002/cctc.202401979  

   Anderson, Shelby R; Gopal, Madan R; Spangler, Abigail P; Jones, Michaela A; Wyllis, D'Jana R; Kunjapur, Aditya M (December 2024, ChemCatChem)

   Abstract Nonstandard amino acids (nsAAs) that are L‐phenylalanine derivatives with aryl ring functionalization have long been harnessed in natural product synthesis, therapeutic peptide synthesis, and diverse applications of genetic code expansion. Yet, to date, these chiral molecules have often been the products of poorly enantioselective and environmentally harsh organic synthesis routes. Here, we reveal the broad specificity of multiple natural pyridoxal 5′‐phosphate (PLP)‐dependent enzymes, specifically an L‐threonine transaldolase, a phenylserine dehydratase, and an aminotransferase, toward substrates that contain aryl side chains with diverse substitutions. We exploit this tolerance to construct a one‐pot biocatalytic cascade that achieves high‐yield synthesis of 18 diverse L‐phenylalanine derivatives from aldehydes under mild aqueous reaction conditions. We demonstrate the addition of a carboxylic acid reductase module to this cascade to enable the biosynthesis of L‐phenylalanine derivatives from carboxylic acids that may be less expensive or less reactive than the corresponding aldehydes. Finally, we investigate the scalability of the cascade by developing a lysate‐based route for preparative‐scale synthesis of 4‐formyl‐L‐phenylalanine, a nsAA with a bio‐orthogonal handle that is not readily market‐accessible. Overall, this work offers an efficient, versatile, and scalable route with the potential to lower manufacturing costs and democratize synthesis for many valuable nsAAs. 

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3. Catalytic intramolecular hydroamination of aminoallenes using titanium and tantalum complexes of sterically encumbered chiral sulfonamides

   https://doi.org/10.1039/D0DT02557G  

   Sha, Fanrui; Shimizu, Emily A.; Slocumb, Hannah S.; Towell, Sydney E.; Zhen, Yi; Porter, Hanna Z.; Takase, Michael; Johnson, Adam (January 2020, Dalton Transactions)

   Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe 2 ) 4 or Ta(NMe 2 ) 5 to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18-24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33-39%. 

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4. Heck reaction synthesis of anthracene and naphthalene derivatives as traps and clean chemical sources of singlet molecular oxygen in biological systems

   https://doi.org/10.1039/d0pp00153h  

   Oliveira, Marilene Silva; Chorociejus, Gabriel; Angeli, José Pedro; Vila Verde, Giuliana; Aquino, Gilberto L.; Ronsein, Graziella E.; Oliveira, Maurício César; Barbosa, Livea F.; Medeiros, Marisa H.; Greer, Alexander; et al (November 2020, Photochemical & Photobiological Sciences)

   null (Ed.)

   Studies have previously shown that anthracene and naphthalene derivatives serve as compounds for trapping and chemically generating singlet molecular oxygen [O 2 ( 1 Δ g )], respectively. Simple and efficient synthetic routes to anthracene and naphthalene derivatives are needed, for improved capture and release of O 2 ( 1 Δ g ) in cellular environments. Because of this need, we have synthesized a dihydroxypropyl amide naphthlene endoperoxide as a O 2 ( 1 Δ g ) donor, as well as five anthracene derivatives as O 2 ( 1 Δ g ) acceptor. The anthracene derivatives bear dihydroxypropyl amide, ester, and sulfonate ion end groups connected to 9,10-positions by way of unsaturated (vinyl) and saturated (ethyl) bridging groups. Heck reactions were found to yield these six compounds in easy-to-carry out 3-step reactions in yields of 50–76%. Preliminary results point to the potential of the anthracene compounds to serve as O 2 ( 1 Δ g ) acceptors and would be amenable for future use in biological systems to expand the understanding of O 2 ( 1 Δ g ) in biochemistry. 

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5. Pyrrole-stabilized free carbenes generated from alkynyl imidates or aldimines and electrophilic alkynes give pyrrolone- or pyrrole-containing products

   https://doi.org/10.1038/s44160-025-00899-0  

   Xu, Qian; Shi, Jingyang; Hoye, Thomas R (October 2025, Nature Synthesis)

   Pyrrole and 2-pyrrolone derivatives are valuable heterocyclic compounds and while classical condensation methods for their synthesis have a long history, many of the recent developments for their preparation involve the use of transition metal catalysis. Here we report a complementary, metal-free strategy for constructing structurally diverse derivatives of these heterocycles. The key feature of the approach is the in situ creation of a reactive intermediate by an initial facile event that simultaneously generates a pyrrole ring bearing a free carbene. This is straightforwardly accessed via a spontaneous, net [3 + 2] cyclization reaction of a linear alkynyl O-silylimidate or alkynyl aldimine with an electrophilic alkyne. The carbene then undergoes either 1,4-silyl migration (to produce 2-pyrrolone derivatives) or C–H insertion, cycloaddition, cyclopropanation or macrocyclization reactions (leading to pyrrole derivatives). 

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