Divergent Synthesis of Scabrolide A and Havellockate via an exo-exo-endo Radical Cascade.

Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.

Sustainable and practical formation of carbon-carbon and carbon-heteroatom bonds employing organo-alkali metal reagents.

Metal-catalysed cross-coupling reactions are amongst the most widely used methods to directly construct new bonds. In this connection, sustainable and practical protocols, especially transition metal-catalysed cross-coupling reactions, have become the focus in many aspects of synthetic chemistry due to their high efficiency and atom economy. This review summarises recent advances from 2012 to 2022 in the formation of carbon-carbon bonds and carbon-heteroatom bonds by employing organo-alkali metal reagents.

Thujasutchins N and O, two new compounds from the stems and roots of Thuja sutchuenensis.

Two novel secondary metabolites, including one thujopsene-type sesquiterpene designated thujasutchin N (1) and one norlignan named thujasutchin O (2) were obtained from the ethanolic extract of the stems and roots of Thuja sutchuenensis. Among them, thujasutchin O (2) represents the first example of lignan sharing a unique carbon-reduced skeleton with novel acetal functionality. Their structures were unambiguously determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, NMR, and single crystal X-ray diffraction. Both of the isolates were evaluated for their in vitro cytotoxic and antibacterial activities.

Total syntheses of ericifolione and its analogues via a biomimetic inverse-electron-demand Diels-Alder reaction.

Driven by bioinspiration and appreciation of the structure of ericifolione, a biomimetic tautomerization/intermolecular inverse-electron-demand hetero Diels-Alder reaction cascade sequence promoted by sodium acetate to rapidly construct sterically hindered dihydropyran scaffolds was established, which allowed the first straightforward biomimetic total syntheses of ericifolione and its analogues with high simplicity. Moreover, this methodology set the stage for the preparation of relevant natural products or derivatives.

Herbivore-Induced (Z)-3-Hexen-1-ol is an Airborne Signal That Promotes Direct and Indirect Defenses in Tea (Camellia sinensis) under Light.

Tea (Camellia sinensis) is the most popular nonalcoholic beverage worldwide. During cultivation, tea plants are susceptible to herbivores and pathogens, which can seriously affect tea yield and quality. A previous report showed that (Z)-3-hexenol is a potentially efficient defensive substance. However, the molecular mechanism mediating (Z)-3-hexenol signaling in tea plants and the resulting effects on plant defenses remain uncharacterized. To clarify the signaling mechanisms in which (Z)-3-hexenol and light are involved, the gene transcription and metabolite levels were assessed, respectively. This study demonstrated that tea plants rapidly and continuously release (Z)-3-hexen-1-ol in response to an insect infestation. (Z)-3-Hexen-1-ol absorbed by adjacent healthy plants would be converted into three insect defensive compounds: (Z)-3-hexenyl-glucoside, (Z)-3-hexenyl-primeveroside, and (Z)-3-hexenyl-vicianoside identified with laboratory-synthesized standards. Moreover, (Z)-3-hexen-1-ol also activates the synthesis of jasmonic acid to enhance the insect resistance of tea plants. Additionally, a continuous light treatment induces the accumulation of (Z)-3-hexenyl-glycosides. Hence, (Z)-3-hexenol serves as a light-regulated signaling molecule that activates the systemic defenses of adjacent plants. Our study reveals the molecular mechanisms by which biotic and abiotic factors synergistically regulate the signaling functions of herbivore-induced plant volatiles in plants, providing valuable information for future comprehensive analyses of the systemic defense mechanisms in plants.

Sesquiterpenes and Steroids from an Endophytic Eutypella scoparia.

A chemical investigation on the EtOAc extract of the endophytic fungus Eutypella scoparia SCBG-8 led to the isolation of eight new sesquiterpenes eutyscoparins A-H (1-8), one C-28 steroid eutyscoparene A (9), one triterpenoid eutyscoparene B (10), six known terpenoids, and two known steroids. Their structures including absolute configurations were established on the basis of spectroscopic data analysis, single-crystal X-ray diffraction experiments, and electronic circular dichroism (ECD) calculations. Compound 7 displayed antibacterial activity against S. aureus and MRSA (methicillin-resistant Staphylococcus aureus) with MIC values of 6.3 µg/mL.

The Biomimetic Total Syntheses of the Antiplasmodial Tomentosones A and B.

The first biomimetic total syntheses of natural phloroglucinols tomentosones A and B and their analogues have been accomplished. The synthetic strategy primarily referred to the potential biosynthetic precursors and their possible sequence of segments assembly by chemological evolution of the structural entities and enabled rapid access of the titled compounds in a practical fashion.

Biomimetic Total Syntheses of Sanctis A-B with Structure Revision.

The first concise total syntheses of sanctis A and B were reported, and it enabled revision of the structure of sanctis B through single-crystal X-ray diffraction. The established synthetic approach mainly mimics a biosynthetic olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade sequence, offering a viable synthetic methodology to efficiently access sanctis A-B and their analogues.

The First Racemic Total Syntheses of the Antiplasmodials Watsonianones A and B and Corymbone B.

The first biomimetic total syntheses of three biologically meaningful acylphloroglucinols, watsonianones A and B and corymbone B, with potent antiplasmodial activity, were performed. Their total syntheses were carried out through a diversity-oriented synthetic strategy from congener 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione with high step efficiency. The spontaneous enolization/air oxidation of the precursor 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione through a singlet O2-induced Diels-Alder reaction pathway to assemble the key biosynthetic peroxide intermediate is also discussed.

Prenylated stilbenes and flavonoids from the leaves of Cajanus cajan.

Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.

Chemical constituents of the trunks and roots of Thuja sutchuenensis.

Five new compounds including two stilbenes, designated thujasutchins A (1) and B (2), two phenolic compounds namely thujasutchins C (3) and D (4), as well as one sesquiterpene thujasutchin E (5), were isolated from the 95% ethanolic extract from the trunks and roots of Thuja sutchuenensis. Their structures were determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, 1H and 13C NMR (COSY, HSQC, HMBC). Moreover, compounds 1, 3-5 were evaluated for in vitro cytotoxic activities against SF-268, MCF-7, HepG-2, and A549 tumor cell lines.

Structural optimization and antibacterial evaluation of rhodomyrtosone B analogues against MRSA strains.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are well-known as a significant global health challenge. In this study, twenty-two congeners of the natural antibiotic rhodomyrtosone B (RDSB) were synthesized with the aim of specifically enhancing the structural diversity through modifying the pendant acyl moiety. The structure-activity relationship study against various MRSA strains revealed that a suitable hydrophobic acyl tail in the phloroglucinol scaffold is a prerequisite for antibacterial activity. Notably, RDSB analogue 11k was identified as a promising lead compound with significant in vitro and in vivo antibacterial activities against a panel of hospital mortality-relevant MRSA strains. Moreover, compound 11k possessed other potent advantages, including breadth of the antibacterial spectrum, rapidity of bactericidal action, and excellent membrane selectivity. The mode of action study of compound 11k at the biophysical and morphology levels disclosed that 11k exerted its MRSA bactericidal action by membrane superpolarization resulting in cell lysis and membrane disruption. Collectively, the presented results indicate that the novel modified RDSB analogue 11k warrants further exploration as a promising candidate for the treatment of MRSA infections.

Brachyanins A-C, pinene-derived meroterpenoids and phloroglucinol derivative from Leptospermum brachyandrum.

A pair of epimer brachyanins A (1) and B (2), along with a new phloroglucinol brachyanin C (3), were isolated from the leaves of Leptospermum brachyandrum. Brachyanins A (1) and B (2) were the first example of novel meroterpenoid with a unique skeleton that combined a synacrpic acid and a pinene units via a benzyl moiety. Their structures were elucidated through the application of extensive spectroscopic measurements and single-crystal X-ray diffraction analysis and with the absolute configurations of 1 and 2 were confirmed by the quantum chemical CD calculation. The hetero Diels-Alder as the key biotransformation was proposed to account for the biosynthesis of brachyanins A and B sheding light by the potential procursor brachyanin C.

A Bioinspired Cascade Sequence Enables Facile Assembly of Methanodibenzo[b,f][1,5]dioxocin Flavonoid Scaffold.

A remarkable bioinspired EDDA-mediated method for the selective construction of biologically interesting and highly strained bridged methanodibenzo[b,f][1,5]dioxocin flavonoid scaffold was uncovered by starting from a variety of readily available acylphloroglucinol and 2-hydroxycinnamaldehyde substrates. This method merges a fascinating olefin isomerization/hemiacetallization/dehydration/[3 + 3]-type cycloaddition cascade reaction driven by an in situ generated chromenylium intermediate and provides a convenient and viable synthetic strategy for the efficient access of such flavonoid analogues.

Biomimetic-Inspired Syntheses of Myrtucommuacetalone and Myrtucommulone J.

Driven by bioinspiration and appreciation of their structures, the first biomimetic total syntheses with structural revision of the acylphloroglucinols myrtucommulone J and myrtucommuacetalone, two biologically meaningful natural products, were achieved through a biosynthetic hemiacetalization/dehydration/[3 + 3]-type cycloaddition domino sequence with high step efficiency. These syntheses result in a corrected structure for myrtucommulone J.