Bioinspired total synthesis and biological activity of Pegaharine A.

BACKGROUND: Phytopathogens cause various diseases by parasitizing crops, reducing crop yield and resulting in substantial economic losses in agricultural production. A novel type isolated from the perennial herbaceous Peganum harmala L. seeds, ß-carboline alkaloids pegaharine A (PA), has become a hot topic in developing plant-originated green pesticides owing to their significant physiological activities. RESULTS: A scalable bioinspired total synthesis of PA is accomplished in the present work. The systematical biological assay study showed that PA exhibited moderate inhibitory activity against nine tested plant pathogenic fungi and showed significant inhibitory activity in vitro against the three tested plant pathogenic bacteria. Most noteworthy is the inhibitory rates of PA on Xanthomonas oryzae pv. oryzae (Xoo), X. oryzae pv. oryzicola (Xoc) and X. axonopodis pv. citri (Xac) of 93.6%, 92.1% and 86.1%, respectively, which are better than the control drug, bismerthiazol (63.4%, 61.2% and 53.7% at 100 µg mL-1 concentration). Furthermore, the EC50 value of PA against Xoo, Xoc and Xac was 52.2, 60.0 and 65.1 µg mL-1 , respectively, superior to 72.9, 64.2 and 70.1 µg mL-1 of the control drug. Moreover, the anti-Xoo mechanistic studies revealed that PA exerted its antibacterial effects by increasing the permeability of the bacterial membrane, reducing the extracellular polysaccharide content and inducing morphological changes in bacterial cells. CONCLUSION: A novel ß-carboline alkaloid, PA, was prepared by biomimetic total synthesis. Its significant antibacterial activity was closely related to the permeation of bacterial cell membranes, which was confirmed by anti-Xoo mechanistic studies. More importantly, the structure could be regarded as a model for developing novel bactericides. © 2023 Society of Chemical Industry.

Increasing Structural Diversity of Prenylated Chalcones by Two Fungal Prenyltransferases.

Prenylated chalcones are found mainly in plants and exhibit diverse biological and pharmacological activities. Some of these compounds are components of food and dietary supplements with significant health benefits. In plants, they are derived from chalcones by prenylation with membrane-bound prenyltransferases. In this study, we demonstrate prenylations of 10 chalcones by two fungal prenyltransferases (AtaPT/AnaPT) in the presence of dimethylallyl diphosphate. Eleven mono- (1a-10a and 9b) and four diprenylated products (8b, 9c, 10b, and 10c) were obtained. Among them, 12 have new structures (1a, 2a, 4a-6a, 8a, 8b, 9b, 9c, 10a, 10b, and 10c). Most of the obtained prenylated chalcones are products of AnaPT and carry prenyl moieties at ring B. Our study provides an excellent example for increasing structural diversity of plant metabolites with microbial enzymes.

Stereoselective (4 + 3) cycloadditions of allenyl ethers-furans by chiral auxiliaries inducing and evaluation of anti-breast cancer activity.

The medicinal plants were wildly library of natural products in drug discovery. The most active molecules with seven-membered rings skeleton represent a challenge for construction. A stereoselectivity (4 + 3) cycloadditions between allenyl ethers and substituted furans induced by chiral auxiliaries has been investigated. And the results showed significant stereoselectivities and regioselectivities. The optical cycloadducts with an oxygen-substituted seven-membered ring framework were generated by removing chiral auxiliaries under acidic conditions. The antiproliferative activity of the novel compounds displayed moderate antiproliferative effects toward T47D cells.

A Synthetic View on Haedoxans and Related Neolignans From Phryma leptostachya.

Haedoxans are a series of sesquilignan natural products isolated from the traditional insecticidal plant Phryma leptostachya. Given their significant insecticidal activity, haedoxans and related analogs have been considered as potential agents for plant defense. Moreover, these compounds also exhibit promising antifungal, antibacterial, and anticancer activities. The present paper is a review of the structure, biological activity, and chemical synthesis of naturally occurring haedoxan-like molecules.

Reversible Protonic Doping in Poly(3,4-Ethylenedioxythiophene).

In this study, poly(3,4-ethylenedioxythiophene), a benchmark-conducting polymer, was doped by protons. The doping and de-doping processes, using protonic acid and a base, were fully reversible. We predicted possible doping sites along the polymer chain using density functional theory (DFT) calculations. This study sheds potential light and understanding on the molecular design of highly conductive organic materials.

Systemic study on the biogenic pathways of yezo'otogirins: total synthesis and antitumor activities of (±)-yezo'otogirin C and its structural analogues.

A systematic study of the biomimetic pathways to yezo'otogirin C under aerobic and anaerobic conditions has been investigated, and both are found to be feasible pathways to the natural product depending on the physiological conditions. Because of the lower activation energy, the aerobic process would be more favorable when the in vivo oxygen level is high. In the course of this study, a highly efficient synthetic route to (±)-yezo'otogirin C has been established in four steps (31% overall yield) from a readily available compound without using any protecting groups. The natural product and its structural analogues exhibited antitumor activities against several human cancer cell lines and appeared to arrest cell cycles in different phases.

An approach to cyclohepta[b]indoles through an allenamide (4 + 3) cycloaddition-Grignard cyclization-Chugaev elimination sequence.

A strategy for synthesizing highly functionalized cyclohepta[b]indoles through a concise (4 + 3) cycloaddition-cyclization-elimination sequence is described. The cycloaddition features nitrogen-stabilized oxyallyl cations derived from epoxidations of N-aryl-N-sulfonyl-substituted allenamides, while the cyclization and elimination employed an intramolecular Grignard addition and a one-step Chugaev process, respectively.

Bioinspired total synthesis of (±)-yezo'otogirin C.

The first and protective group-free total synthesis of (±)-yezo'otogirin C has been achieved from 3-methyl-4-prenylcyclohex-2-enone in eight steps with 23% overall yield. The tricyclic core of (±)-yezo'otogirin C was established via a bioinspired oxidative cascade cyclization strategy using Mn(II)/Mn(III) and O2, followed by reduction of the peroxy-bridged intermediate using thiourea in refluxing methanol.

Ynamides in ring forming transformations.

The ynamide functional group activates carbon-carbontriple bonds through an attached nitrogen atom that bears an electron-withdrawing group. As a result, the alkyne has both electrophilic and nucleophilic properties. Through the selection of the electron-withdrawing group attached to nitrogen, chemists can modulate the electronic properties and reactivity of ynamides, making these groups versatile synthetic building blocks. The reactions of ynamides also lead directly to nitrogen-containing products, which provides access to important structural motifs found in natural products and molecules of medicinal interest. Therefore, researchers have invested increasing time and research in the chemistry of ynamides in recent years. This Account surveys and assesses new organic transforma-tions involving ynamides developed in our laboratory and in others around the world. We showcase the synthetic power of ynamides for rapid assembly of complex molecular structures. Among the recent reports of ynamide transformations, ring-forming reactions provide a powerful tool for generating molecular complexity quickly. In addition to their synthetic utility, such reactions are mechanistically interesting. Therefore, we focus primarily on the cyclization chemistry of ynamides. This Account highlights ynamide reactions that are useful in the rapid synthesis of cyclic and polycyclic structural manifolds. We discuss the mechanisms active in the ring formations and describe representative examples that demonstrate the scope of these reactions and provide mechanistic insights. In this discussion, we feature examples of ynamide reactions involving radical cyclizations, ring-closing metathesis, transition metal and non-transition metal mediated cyclizations, cycloaddition reactions, and rearrangements. The transformations presented rapidly introduce structural complexity and include nitrogen within or in close proximity to a newly formed ring (or rings). Thus, ynamides have emerged as powerful synthons for nitrogen-containing heterocycles and nitrogen-substituted rings, and we hope this Account will promote continued interest in the chemistry of ynamides.

Formal syntheses of (±)-platensimycin and (±)-platencin via a dual-mode Lewis acid induced cascade cyclization approach.

A mild and efficient dual-mode Lewis acid induced Diels-Alder (DA)/carbocyclization cascade cyclization reaction has been developed for construction of the tricyclic core of ent-kaurenoids in one pot with the aid of a theoretical study on the π,σ-Lewis acidities of a variety of Lewis acids. With ZnBr2 as the dual-mode Lewis acid, a series of substituted enones and dienes underwent DA/carbocyclization cascade cyclization reaction smoothly at room temperature and provided the tricyclic cyclized products in one pot with good yields and high diastereoselectivity. The tricyclic cyclized product has been successfully utilized as a common intermediate for formal syntheses of (±)-platensimycin and (±)-platencin.

Intramolecular oxyallyl-carbonyl (3 + 2) cycloadditions.

Cycloadditions involving oxyallyl intermediates typically require an electron-rich diene or alkene, but we have discovered the first examples of the cycloaddition of heteroatom-stabilized oxyallyls onto carbonyl groups. An oxazolidinone-substituted oxyallyl undergoes chemoselective (3 + 2) cycloaddition onto the carbonyl group of a tethered dienone in preference to formation of the expected (4 + 3) cycloadduct. Density functional theory calculations indicated that the (3 + 2) cycloaddition takes place through a concerted, highly asynchronous mechanism. The transition state features simultaneous interactions of the oxyallyl LUMO with the carbonyl π and lone-pair orbitals, making this reaction "hemipseudopericyclic" (halfway between purely pericyclic and purely pseudopericyclic). Further (3 + 2) cycloadditions involving tethered phenyl ketones and a tethered enone were predicted theoretically and verified experimentally.

α-Aryl-substituted allenamides in an imino-Nazarov cyclization cascade catalyzed by Au(I).

An imino-Nazarov cyclization using α-aryl-substituted allenamides is described. This gold(I)-catalyzed cascade is efficient and regioselective in constructing a diverse array of synthetically useful aromatic-ring fused cyclopentenamides. The success in this transformation represents a solution to the challenge in establishing an imino-Nazarov cyclization process.

Responsive two-photon induced europium emission as fluorescent indicator for paralytic shellfish saxitoxin.

A water-soluble europium(III) complex (1) has been synthesized and demonstrated to be a specific fluorescence probe for the paralytic shellfish toxin saxitoxin, a neurotoxin that blocks the voltage-gated sodium channels on cell membranes. Saxitoxin binds to the europium complex (K(B) = 6.1 × 10(4) M(-1)) and triggers a two-photon induced f-f emission enhancement by over 100% and increases the two-photon absorption cross-section from 9 to 36 GM.