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1. Cooperative Biocatalysis Enables Assembly of a Prenylated Indole Alkaloid

   https://doi.org/10.1002/adsc.202300980  

   Hohlman, Robert M. ; Keramati, Nikki R. ; Sherman, David H. ( November 2023 , Advanced Synthesis & Catalysis)

   The hapalindole‐type metabolites have garnered significant interest due to their diverse biological activities and unique chemical structures. Recently, the biosynthesis of this family of indole alkaloids has been uncovered and shown to involve a rare biocatalytic Cope rearrangement. Previously, we demonstratedcis‐indole isonitrile C‐3 normal geranylation using FamD2. Thus, we sought to explore further the reaction potential with this substrate and dimethylallyl pyrophosphate (DMAPP) using prenyltransferases and cyclases from the hapalindole biosynthetic pathways. Here, we report a new compound derived from an unexpected biosynthetic Cope rearrangement, which expands further the scope of metabolites generated from cyanobacterial Stig cyclases.

    

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2. Enantioselective Catalysis of an Anionic Oxy‐Cope Rearrangement Enabled by Synergistic Ion Binding

   https://doi.org/10.1002/ijch.201900168  

   Kennedy, C. Rose ; Choi, Bo Young ; Reeves, Mary‐Grace R. ; Jacobsen, Eric N. ( March 2020 , Israel Journal of Chemistry)

   Charge‐accelerated rearrangements present interesting challenges to enantioselective catalysis, due in large part to the competing requirements for maximizing reactivity (ion‐pair separation) and stereochemical communication. Herein, we describe application of a synergistic ion‐binding strategy to catalyze the anionic oxy‐Cope rearrangement of a symmetricbis‐styrenyl allyl alcohol in up to 75 : 25 e.r. Structure‐reactivity‐selectivity relationship studies, including linear free‐energy‐relationship analyses, with bifunctional urea catalysts indicate that H‐bonding and cation‐binding interactions act cooperatively to promote the chemo‐ and enantioselective [3,3]‐rearrangement. Implications for catalyst designs applicable to other transformations involving oxyanionic intermediates are discussed.

    

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3. Metallocarbenes as Substituents in 8‐Electron Electrocyclizations

   https://doi.org/10.1002/ejoc.202301183  

   Cao, Yumeng ; Kong, Wang‐Yeuk ; DeSnoo, William ; Tantillo, Dean J. ( January 2024 , European Journal of Organic Chemistry)

   Density functional theory was used to elucidate the mechanism and the pericyclicity of chromium‐catalyzed bicyclization reactions that purportedly involve 8‐electron electrocyclization steps. Our computational results indicate that these reactions do indeed proceed via 8‐electron electrocyclization rather than an alternative pathway involving 4‐electron electrocyclization followed by Cope rearrangement. The role of C=[M] groups on the electrocyclization, specifically its pericyclicity, was examined in detail using modern theoretical tools.

    

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4. N -Acyl pyrroles: chemoselective pyrrole dance vs. C–H functionalization/aroylation of toluenes

   https://doi.org/10.1039/D1QO00944C  

   Wang, Huan ; Mao, Jianyou ; Shuai, SuJuan ; Chen, Shuguang ; Zou, Dong ; Walsh, Patrick J. ; Li, Jie ( October 2021 , Organic Chemistry Frontiers)

   Chemoselectivity is one of the most challenging issues facing the chemical sciences. In this study, the first highly chemoselective reactions of N -acylpyrroles via either an anionic Fries rearrangement (pyrrole dance) or a C–H functionalization of toluene to provide aryl benzyl ketones are advanced. This efficient and operationally simple approach enables the synthesis of either 2-aroylpyrroles or aryl benzyl ketones in good to excellent yields under transition metal-free conditions. The choice of base plays a crucial role in controlling the chemoselectivity. The aroylation of toluene derivatives was observed with N -acylpyrroles when subjected to KN(SiMe 3 ) 2 , while anionic Fries rearrangement products were produced with LiN(SiMe 3 ) 2 . Surprisingly, cross-over experiments indicate that the anionic Fries rearrangement is an intermolecular process. The aroylation reaction has the advantage over Weinreb amide chemistry in that it does not require preformed organometallic reagents or cryogenic temperatures. 

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5. Evaluating impacts of syntenic block detection strategies on rearrangement phylogeny using Mycobacterium tuberculosis isolates

   https://doi.org/10.1093/bioinformatics/btad024  

   Elghraoui, Afif ; Mirarab, Siavash ; Swenson, Krister M. ; Valafar, Faramarz ; Schwartz, ed., Russell ( January 2023 , Bioinformatics)

   The phylogenetic signal of structural variation informs a more comprehensive understanding of evolution. As (near-)complete genome assembly becomes more commonplace, the next methodological challenge for inferring genome rearrangement trees is the identification of syntenic blocks of orthologous sequences. In this article, we studied 94 reference quality genomes of primarily Mycobacterium tuberculosis (Mtb) isolates as a benchmark to evaluate these methods. The clonal nature of Mtb evolution, the manageable genome sizes, along with substantial levels of structural variation make this an ideal benchmarking dataset.

   We tested several methods for detecting homology and obtaining syntenic blocks and two methods for inferring phylogenies from them, then compared the resulting trees to the standard method’s tree, inferred from nucleotide substitutions. We found that, not only the choice of methods, but also their parameters can impact results, and that the tree inference method had less impact than the block determination method. Interestingly, a rearrangement tree based on blocks from the Cactus whole-genome aligner was fully compatible with the highly supported branches of the substitution-based tree, enabling the combination of the two into a high-resolution supertree. Overall, our results indicate that accurate trees can be inferred using genome rearrangements, but the choice of the methods for inferring homology requires care.

   Analysis scripts and code written for this study are available at https://gitlab.com/LPCDRP/rearrangement-homology.pub and https://gitlab.com/LPCDRP/syntement.

   Supplementary data are available at Bioinformatics online.

    

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