Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes.

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant.

Synthesis of portimines reveals the basis of their anti-cancer activity.

Marine-derived cyclic imine toxins, portimine A and portimine B, have attracted attention because of their chemical structure and notable anti-cancer therapeutic potential. However, access to large quantities of these toxins is currently not feasible, and the molecular mechanism underlying their potent activity remains unknown until now. To address this, a scalable and concise synthesis of portimines is presented, which benefits from the logic used in the two-phase terpenoid synthesis along with other tactics such as exploiting ring-chain tautomerization and skeletal reorganization to minimize protecting group chemistry through self-protection.

KSO-Mediated Radical Cyclization of 1,6-Enyne for the Synthesis of Diiodonated γ-Lactams.

A novel and convenient KSO-mediated diiodo cyclization of 1,6-enynes for the facile synthesis of functionalized γ-lactam derivatives has been developed. This reaction features mild and transition-metal-free conditions, which offer a green and efficient entry to synthetically important γ-lactam scaffolds. Mechanistic studies suggest that iodide radicals initiate the cascade cyclic transformation.

Silver(I)-Catalyzed Oxidative Cyclopropanation of 1,6-Enynes: Synthesis of 3-Aza-bicyclo[3.1.0]hexane Derivatives.

A simple Ag(I)-catalyzed oxidative cyclopropanation of heteroatom-tethered 1,6-enynes for the establishment of valuable functionalized 3-aza-bicyclo[3.1.0]hexane is presented, which allows the formation of multiple chemical bonds in one step under 20 mol % silver(I) catalysts and air conditions.

Methyl 6-O-cinnamoyl-α-d-glucopyranoside Ameliorates Acute Liver Injury by Inhibiting Oxidative Stress Through the Activation of Nrf2 Signaling Pathway.

Excessive stimulation of hepatotoxins and drugs often lead to acute liver injury, while treatment strategies for acute liver injury have been limited. Methyl 6-O-cinnamoyl-α-d-glucopyranoside (MCGP) is a structure modified compound from cinnamic acid, a key chemical found in plants with significant antioxidant, anti-inflammatory, and antidiabetic effects. In this study, we investigated the effects and underlying mechanisms of MCGP on acetaminophen (APAP)- or carbon tetrachloride (CCl)-induced acute liver injury.

A Removable Acyl Group Promoted the Intramolecular Dehydro-Diels-Alder Reaction of Styrene-Ynes: Highly Chemoselective Synthesis of Aryldihydronaphthalene Derivatives.

A removable acyl group promoted the intramolecular didehydro-Diels-Alder reaction of styrene-ynes under mild reaction conditions is proposed. The reaction is free of metals and catalysts, is easy to perform, and exhibits good functional group tolerance, providing a highly chemoselective approach for obtaining the valuable aryldihydronaphthalene derivatives.

A mild tetradehydro-Diels-Alder reaction of aryldiyne compounds affords exclusively linear products.

The thermal tetradehydro-Diels-Alder (TDDA) reaction for the synthesis of polysubstituted aromatic compounds remains underestimated probably due to the harsh conditions and multiproduct results. Herein, a mild intramolecular TDDA reaction of aryldiyne compounds is presented with linear naphthalenes only, exhibiting good functional group tolerance. The reaction is easy to operate and amenable to multigram-scale synthesis.

Unprecedented polycyclic polyprenylated acylphloroglucinols with anti-Alzheimer's activity from St. John's wort.

Hyperforones A-J (), ten degraded and reconstructed polycyclic polyprenylated acylphloroglucinols (PPAPs) with six different types of unusual architectures, were isolated from (St. John's wort). Compound is characterized by an unprecedented 1,5-epoxyfuro[3',4':1,5]cyclopenta[1,2-]oxecine ring system; compounds and represent the first PPAPs with a contracted B-ring leading to the unique 5/5 core skeletons; compound , a proposed biosynthetic precursor of , is defined by an oxonane-2,7-dione architecture; compound features an unusual spiro[furo[3',4':1,5]cyclopenta[1,2-]oxepine-3,2'-oxetane] ring system; compounds possess a rare macrocyclic lactone ring in addition to the newly formed C-ring; and compounds and contain a newly formed six-membered C-ring, which constructed the unexpected 6/6 scaffold with the B-ring.

Terpene-Shikimate conjugated meroterpenoids from the endophytic fungus Guignardia mangiferae.

Nine undescribed shikimate-conjugated meroterpenes, as well as nine known compounds, were isolated from solid cultures of the fungus Guignardia mangiferae, an endophyte obtained from the leaves of Dendrobium nobile. The structures of these undescribed compounds were characterized by analyses of their 1D and 2D NMR and HRESIMS data, and their absolute configurations were assigned by single-crystal X-ray crystallography, electronic circular dichroism (ECD) calculations, modified Mosher's method, and Mo(OCOCH)-induced ECD experiments. Of these compounds, mangnardone A represents the first example of terpene-shikimate-conjugated meroterpenoid with a hydroxy group at C-5.

Practical access to fluorescent 2,3-naphthalimide derivatives via didehydro-Diels-Alder reaction.

A practical and efficient approach for the synthesis of fluorescent 2,3-naphthalimide derivatives has been developed from readily available starting materials via an intramolecular didehydro-Diels-Alder reaction, which proceeded well under room temperature, exhibiting a wide substrate scope and good functional group tolerance. The practicability of this methodology has been verified by one-step synthesis of the environmentally sensitive fluorophore 6-DMN on a gram scale with a shorter time, fewer steps and less waste disposal, and without the utilization of toxic transition metals. The present experimental and computational studies support the crucial role of the propiolimide moiety in the transformation.

Piperazine-2,5-dione derivatives and an α-pyrone polyketide from Penicillium griseofulvum and their immunosuppression activity.

Four undescribed piperazine-2,5-dione derivatives designated janthinolides C-F, and an α-pyrone-containing polyketide namely trichopyrone C, were isolated from the extract of the fungus Penicillium griseofulvum along with four known products. Among them, janthinolide C represents the first naturally occured piperazine-2,5-dione analogue featuring a cleavaged piperazinedione ring with an oxime group, while the structure of janthinolide D possesses a rare N-methoxy group in natural products. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, theoretical NMR and ECD calculations, Snatzke's method, and modified Mosher's method.

Synthesis of Succinimides via Intramolecular Alder-Ene Reaction of 1,6-Enynes.

A novel and convenient method has been developed for the facile synthesis of functionalized succinimide derivatives via intramolecular Alder-ene reaction of 1,6-enynes. This reaction features mild and metal-free reaction conditions, which offers a green and efficient entry to synthetically important succinimide scaffolds. Preliminary mechanistic studies suggest that a diradical intermediate might be involved in this transformation.

Dimericchalasine A and Amichalasines D and E: Unexpected Cytochalasan Homodimer and Heterotrimers from PG-1.

The study of led to the isolation of three unprecedented cytochalasans (-). Dimericchalasine A () is the first cytochalasan homodimer fused by a C-20/C-20' single bond. Amichalasines D () and E () represent a new type of cytochalasan heterotrimer with a decacyclic 5/6/11/5/5/6/5/12/6/5 ring system.

Mangiterpenes A-C and 2',3'-seco-manginoid C, four sesquiterpene/monoterpene-shikimate-conjugated spirocyclic meroterpenoids from Guignardia mangiferae.

Mangiterpenes A-C and 2',3'-seco-manginoid C, four undescribed sesquiterpene/monoterpene-shikimate-conjugated meroterpenoids with spiro ring systems, were isolated from Guignardia mangiferae. The structures and absolute configurations of these compounds were established by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Mangiterpenes A-C represent the first examples of sesquiterpene-shikimate-conjugated spirocyclic meroterpenoids, and 2',3'-seco-manginoid C features an unexpected 2',3'-seco-manginoids skeleton.

Hyperforatins L-U: Prenylated acylphloroglucinols with a terminal double bond from Hypericum perforatum L. (St John's Wort).

Hyperforatins L-U, ten undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) bearing a terminal double bond, together with a known compound hypericumoxide J, were isolated from the aerial parts of Hypericum perforatum L. Their structures were elucidated by spectroscopic methods, including HRESIMS, IR, UV, and NMR (H, C, DEPT, HSQC, HMBC, H-H COSY, and NOESY experiments). Their absolute configurations were determined by comprehensive analyses of their experimental ECD spectra in conjunction with a modified Mosher's method.

Phenolic C-Glycosides and Aglycones from Marine-Derived Aspergillus sp. and Their Anti-Inflammatory Activities.

A chemical investigation of the secondary metabolites of a marine-derived Aspergillus sp. led to the isolation and characterization of 13 phenolic compounds, including 10 new compounds (1-10). Seven new compounds (1-7) are unusual phenolic C-glycosides, while the other new compounds (8-10) are structurally related aglycones.

Amiaspochalasins A-H, Undescribed Aspochalasins with a C-21 Ester Carbonyl from Aspergillus micronesiensis.

Amiaspochalasins A-H (1-8), eight undescribed aspochalasins, and trichalasin D (9), a known analogue, were isolated from the solid culture of Aspergillus micronesiensis. Compounds 1-9 are aspochalasins with a C-21 ester carbonyl, and their structures were determined by spectroscopic data, X-ray crystallographic analyses, electronic circular dichroism calculations, and chemical methods. The CH-25 in compound 1 is located at C-16 rather than C-14 in the previously reported aspochalasins, endowing 1 with an unexpected carbon skeleton.

Anti-Inflammatory Activities of Leaf Oil from and .

The study determined the chemical constituents and anti-inflammatory effects of leaf oil from (CS-LO) that has been used in folk medicine to treat various symptoms including inflammation. The anti-inflammatory effects of the oil were evaluated by LPS-stimulated RAW264.7 cells and the Carr-induced hind mouse paw edema model, respectively.

(±)-Peniorthoesters A and B, Two Pairs of Novel Spiro-Orthoester en-antiomers With an Unusual 1,4,6-Trioxaspi-ro[4.5]decane-7-One Unit From .

(±)-Peniorthoesters A and B (± and ±), two pairs of unprecedented spiro-orthoester enantiomers with a 1,4,6-trioxaspiro[4. 5]decane-7-one unit, were obtained from . Their structures were determined by spectroscopic methods, X-ray diffraction analyses, and ECD calculations.

Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum.

Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring.

Fusicoccane-Derived Diterpenoids from Alternaria brassicicola: Investigation of the Structure-Stability Relationship and Discovery of an IKKβ Inhibitor.

The structure-stability relationships of 1-6 were investigated to show that 1 converted to 5 via a kinetic, solution-mediated autoxidation. In addition, alterbrassicene A (7), a fusicoccane-derived diterpenoid bearing an unprecedented 5/9/4-fused carbocyclic skeleton with a rare fused 2-cyclobuten-1-one motif, was characterized from Alternaria brassicicola. Its absolute structure was elucidated by spectroscopic analyses and quantum chemical calculations.

Kinsenoside: A Promising Bioactive Compound from Anoectochilus Species.

Kinsenoside is a main active component isolated from plants of the genus Anoectochilus, and exhibits many biological activities and pharmacological effects, including hepatoprotective, anti-hyperglycemic, anti-hyperliposis, anti-inflammatory, vascular protective and anti-osteoporosis effects and so on, which is contributing to its promising potency in disease treatments. This review aims to recapitulate the pharmacological functions of kinsenoside, as well as its source, extraction, identification, quantitative analysis, pharmacokinetics, synthesis and patent information. The data reported in this work can confirm the therapeutic potential of kinsenoside and provide useful information for further new drug development.

Asperversiamides, Linearly Fused Prenylated Indole Alkaloids from the Marine-Derived Fungus Aspergillus versicolor.

Asperversiamides A-H (1-8), eight linearly fused prenylated indole alkaloids featuring an unusual pyrano[3,2- f]indole unit, were isolated from the marine-derived fungus Aspergillus versicolor. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and optical rotation (OR) calculations. The relative configuration of C-21 of iso-notoamide B was herein revised, and a new methodology for preliminarily determining if the relative configuration of the bicyclo[2.