Comparative genomics of the niche-specific plant pathogen Streptomyces ipomoeae reveal novel genome content and organization.

IMPORTANCE: While most plant-pathogenic Streptomyces species cause scab disease on a variety of plant hosts, Streptomyces ipomoeae is the sole causative agent of soil rot disease of sweet potato and closely related plant species. Here, genome sequencing of virulent and avirulent S. ipomoeae strains coupled with comparative genomic analyses has identified genome content and organization features unique to this streptomycete plant pathogen. The results here will enable future research into the mechanisms used by S. ipomoeae to cause disease and to persist in its niche environment.

A decade review of triphosgene and its applications in organic reactions.

This review article highlights selected advances in triphosgene-enabled organic synthetic reactions that were reported in the decade of 2010-2019. Triphosgene is a versatile reagent in organic synthesis. It serves as a convenient substitute for the toxic phosgene gas. Despite its first known preparation in the late 19th interestingly began only three decades ago. Despite the relatively short history, triphosgene has been proven to be very useful in facilitating the preparation of a vast scope of value-added compounds, such as organohalides, acid chlorides, isocyanates, carbonyl addition adducts, heterocycles, among others. Furthermore, applications of triphosgene in complex molecules synthesis, polymer synthesis, and other techniques, such as flow chemistry and solid phase synthesis, have also emerged in the literature.

Mechanistic Perspectives in the Regioselective Indole Addition to Unsymmetrical Silyloxyallyl Cations.

Our investigations on the reaction mechanism to account for regioselectivity on the addition of indoles to unsymmetrical silyloxyallyl cations are reported. Using both experimental and computational methods, we confirmed the significance of steric effects from the silyl ether group toward directing the inward approach of indoles, leading to nucleophilic attack at the less substituted electrophilic α'-carbon. The role of residual water toward accelerating the rate of reaction is established through stabilization of the participating silyloxyallyl cation.

Synthesis of Vicinal Dichlorides via Activation of Aliphatic Terminal Epoxides with Triphosgene and Pyridine.

Herein we report a novel synthetic reaction to convert unactivated terminal aliphatic epoxide to alkyl vicinal dichloride based on triphosgene-pyridine activation. Our methodology is operationally simple and readily tolerated by a broad of scope of substrates as well as protecting groups. Furthermore, these mild conditions generally yield clean reaction mixtures that are free of byproducts upon aqueous workup.

Enantioselective Functionalization of Enamides at the ß-Carbon Center with Indoles.

We report an enantioconvergent approach for the functionalization of enamides at the ß-carbon atom, which involves a chiral Brønsted acid induced tautomerization of 2-amidoallyl into 1-amidoallyl cations. These putative reactive intermediates were produced by ionization of racemic α-hydroxy enamides with a chiral Brønsted acid and captured with substituted indoles in a highly regio- and enantioselective manner.

Brønsted Acid Catalyzed Synthesis of Functionalized 1,4- and 1,6-Dicarbonyl Monosilyl Enol Ethers under Operationally Practical Conditions.

Herein, we report an improved protocol for the concise synthesis of functionalized 1,4- and 1,6-dicarbonyl-derived monosilyl enol ethers via ionization of α'-hydroxy silyl enol ethers to generate unsymmetrical silyloxyallyl cations that were subsequently captured by TBS silyl enolates. These transformations were efficiently performed in acetonitrile at room temperature by employing pyridinium triflate as a catalyst. Our new reaction conditions are operationally more practical and broaden the accessibility of various 1,4- and 1,6-dicarbonyl groups, which include diketone, ketoester, and ketothioester functionalities.

Synthesis of Vinyl Chlorides via Triphosgene-Pyridine Activation of Ketones.

Herein, we describe a mild method to prepare aliphatic and aromatic vinyl chlorides from their corresponding ketones via triphosgene-pyridine activation in dichloromethane at reflux. The mechanism of this reaction is proposed to involve formation of a putative α-chloro pyridinium carbamate intermediate, which appeared to readily undergo E2 elimination in the presence of pyridine.

Brønsted acid catalyzed α'-functionalization of silylenol ethers with indoles.

A new method which enables carbon-carbon bond formation at the α'-position of silylenol ethers by using catalytic amounts of pyridinium triflate is reported. This chemistry successfully produces, structurally challenging, highly substituted indole-containing silylenol ethers in excellent yields with complete regiocontrol, presumably through silyloxyallyl cation intermediates. Despite the use of Brønsted acid, the silylenol ether moiety does not undergo protodesilylation, thus underscoring the very mild reaction conditions.

Triphosgene-amine base promoted chlorination of unactivated aliphatic alcohols.

Unactivated α-branched primary and secondary aliphatic alcohols have been successfully transformed into their corresponding alkyl chlorides in high yields upon treatment with a mixture of triphosgene and pyridine in dichloromethane at reflux. These mild chlorination conditions are high yielding, stereospecific, and well tolerated by numerous sensitive functionalities. Furthermore, no nuisance waste products are generated in the course of the reactions.

Directing the Stereoselectivity of the Claisen Rearrangement to Form Cyclic Ketones with Full Substitution at the α-Positions.

We report an enantioselective synthesis of cyclic ketones with full substitutions at the α-positions in a highly diastereoselective manner. Our method is achieved by subjecting substrate motifs in 2-allyloxyenones to chiral organomagnesium reagents, which trigger the Claisen rearrangement upon direct 1,2-carbonyl addition. The observed diastereoselectivity of the allyl migration is proposed to originate from the intramolecular chelation of the magnesium alkoxide to the allyloxy moiety.

Exploring post-translational arginine modification using chemically synthesized methylglyoxal hydroimidazolones.

The methylglyoxal-derived hydroimidazolones (MG-Hs) comprise the most prevalent class of non-enzymatic, post-translational modifications of protein arginine residues found in nature. These adducts form spontaneously in the human body, and are also present at high levels in the human diet. Despite numerous lines of evidence suggesting that MG-H-arginine adducts play critical roles in both healthy and disease physiology in humans, detailed studies of these molecules have been hindered by a lack of general synthetic strategies for their preparation in chemically homogeneous form, and on scales sufficient to enable detailed biochemical and cellular investigations. To address this limitation, we have developed efficient, multigram-scale syntheses of all MG-H-amino acid building blocks, suitably protected for solid-phase peptide synthesis, in 2-3 steps starting from inexpensive, readily available starting materials. Thus, MG-H derivatives were readily incorporated into oligopeptides site-specifically using standard solid-phase peptide synthesis. Access to synthetic MG-H-peptide adducts has enabled detailed investigations, which have revealed a series of novel and unexpected findings. First, one of the three MG-H isomers, MG-H3, was found to possess potent, pH-dependent antioxidant properties in biochemical and cellular assays intended to replicate redox processes that occur in vivo. Computational and mechanistic studies suggest that MG-H3-containing constructs are capable of participating in mechanistically distinct H-atom-transfer and single-electron-transfer oxidation processes. Notably, the product of MG-H3 oxidation was unexpectedly observed to disassemble into the fully unmodified arginine residue and pyruvate in aqueous solution. We believe these observations provide insight into the role(s) of MG-H-protein adducts in human physiology, and expect the synthetic reagents reported herein to enable investigations into non-enzymatic protein regulation at an unprecedented level of detail.

Copper(I)-Catalyzed Synthesis of Unsymmetrical All-Carbon Bis-Quaternary Centers at the Opposing α-Carbons of Cyclohexanones.

We describe a new synthetic reaction that generates all-carbon bis-quaternary centers at the opposing side of α-carbons in cyclohexanone with four different substituents in a controlled manner. Catalyzed by Cu(MeCN)4BF4 salt, this chemistry is proposed to proceed via an intermediacy of unsymmetrical O-allyl oxyallyl cations, which undergo a sequence of regioselective nucleophilic addition with substituted indoles and diastereoselective Claisen rearrangement in a single synthetic operation. The stereochemical outcome of the products features the cis diastereorelationship between the two aryl groups at the α,α'-positions.

Recent Advancements in Pyrrole Synthesis.

This review article features selected examples on the synthesis of functionalized pyrroles that were reported between 2014 and 2019. Pyrrole is an important nitrogen-containing aromatic heterocycle that can be found in numerous compounds of biological and material significance. Given its vast importance, pyrrole continues to be an attractive target for the development of new synthetic reactions. The contents of this article are organized by the starting materials, which can be broadly classified into four different types: substrates bearing π-systems, substrates bearing carbonyl and other polar groups, and substrates bearing heterocyclic motifs. Brief discussions on plausible reaction mechanisms for most transformations are also presented.

Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates.

An expedient synthesis of highly substituted tetrahydrobenzofuran via an unsymmetrical silyloxyallyl cation is reported. Conveniently generated under catalytic Brønsted acid conditions, nucleophilic capture of this reactive intermediate by silylenolate, followed by Paal-Knorr cascade cyclization in the presence of tosic acid monohydrate effectively constructed the tetrahydrobenzofuran core in a single synthetic step.

Correction: Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates.

Correction for 'Synthesis of functionalized tetrahydropyrans via cascade cycloaddition involving silyloxyallyl cation intermediates' by Fatimat O. Badmus et al., Chem. Commun., 2020, 56, 5034-5037, DOI: .

Brønsted Acid-Catalyzed Formal [2 + 2 + 1] Annulation for the Modular Synthesis of Tetrahydroindoles and Tetrahydrocyclopenta[ b]pyrroles.

An expedient synthesis of tetrahydroindoles and tetrahydrocyclopenta[ b]pyrroles, highlighted by Brønsted acid catalyzed formal [2 + 2 + 1] annulation reaction, is reported. Using three readily accessible reaction components, i.e., an electrophilic species in silyloxyallyl cations and two distinct nucleophiles in silylenol ethers and amines, our chemistry enables the assembly and functionalization of these biologically important N-heterocycles in a highly modular manner.

Triphosgene and DMAP as Mild Reagents for Chemoselective Dehydration of Tertiary Alcohols.

The utility of triphosgene and DMAP as mild reagents for chemoselective dehydration of tertiary alcohols is reported. Performed in dichloromethane at room temperature, this reaction is readily tolerated by a broad scope of substrates, yielding alkenes preferentially with the (E)-geometry. While formation of the Hofmann products is generally favored, a dramatic change in alkene selectivity toward the Zaitzev products is observed when the reaction is carried out in dichloroethane at reflux.

Electrophile-induced ether transfer: stereoselective synthesis of 2,6-disubstituted-3,4-dihydropyrans.

Stereoselective synthesis of trans-2,6-disubstituted-3,4-dihydropyrans has been achieved from a simple homoallylic alkoxyether via a three-step sequence: electrophile-induced ether transfer, cyclization, and functionalization, which is highlighted by a rare example of Ferrier rearrangement of allylic ether. This methodology was successfully implemented for the asymmetric synthesis of a C7-C17 fragment of swinholide A.

Regioselective Functionalization of Enamides at the α-Carbon via Unsymmetrical 2-Amidoallyl Cations.

A new method to functionalize enamides via an intermediacy of unsymmetrical 2-amidoallyl cations is reported. Generated under mild Brønsted acid catalysis, these reactive species were found to undergo addition with various nucleophiles at the less substituted α-carbon to produce highly substituted enamides in high yields with complete control of regioselectivity.

Electrophile-induced ether transfer: a new approach to polyketide structural units.

[Structure: see text] A strategically novel approach to the formation of syn-1,3-diol mono- and diethers through electrophilic activation of homoallylic alkoxymethyl ethers has been developed. The resulting polyketide-like synthetic fragments are generated in good yield and with excellent stereocontrol. A chairlike transition state is proposed to account for the high stereoselectivity. Varying the conditions of the reaction workup results in the efficient generation of mono- and diether containing structural units common to polyketide natural products.