Total Syntheses of β- and γ-Naphthocyclinones.

After half a century from their isolation in 1974, we report the first total syntheses of β- and γ-naphthocyclinones, two dimeric pyranonaphthoquinones featuring an unusual bicyclo[3.2.1]octadienone core.

One-Pot Synthesis of Functionalized Benzotropones via a Phthalide Ring-Opening/Intramolecular Aldol Condensation Cascade.

A one-pot protocol was developed for the synthesis of functionalized benzotropone derivatives via a nucleophilic phthalide ring opening by a 5-lithiated dioxinone derivative, followed by an intramolecular aldol condensation. The method demonstrates exceptional versatility with diverse substrates, yielding a variety of functionalized benzotropones. Subsequent transformations of the obtained benzotropone derivatives were explored for their potential applications.

Total Syntheses of Sparsomycin and Sparoxomycins A and A via Sulfenate-Anion-Mediated Iterative C-S Bond Formation.

The total synthesis of the pyrimidinylpropenamide antibiotics sparsomycin and sparoxomycins A and A has been achieved. The synthesis of sparsomycin relies on the iterative nucleophilic attack of sulfenate anions on alkyl halides to construct the dithioacetal monoxide chain with high diastereoselectivity. Subsequently, the reagent-controlled diastereoselective oxidation of the terminal sulfide moiety of sparsomycin directly provides sparoxomycins A and A.

Enantioselective Total Syntheses of Preussomerins: Control of Spiroacetal Stereogenicity by Photochemical Reaction of a Naphthoquinone through 1,6-Hydrogen Atom Transfer.

We report the enantioselective total syntheses of preussomerins EG , EG , and EG . The key transformation is a stereospecific photochemical reaction involving 1,6-hydrogen atom transfer to achieve retentive replacement of a C-H with a C-O bond, enabling otherwise-difficult control of the spiroacetal stereogenic center.

synthesis of dimerization-ready flavan unit intramolecular Pummerer/Friedel-Crafts cascade.

We describe the synthesis of a dimerization-ready flavan derivative the Pummerer/Friedel-Crafts cascade. This method allowed facile access to oligomeric proanthocyanidin natural products. The total synthesis of procyanidin B4 was achieved by this strategy.

Total Synthesis of Parameritannin A2, a Branched Epicatechin Tetramer with Two Double Linkages.

The first total synthesis of parameritannin A2 (1), a branched epicatechin (EC) tetramer is reported. The "phloroglucinol trick" was used to circumvent two synthetic issues encountered when assembling four EC units, namely, the steric constraint and the formation of the C4-C6 interflavan linkage. As a substructure of the middle EC unit, phloroglucinol enabled the single-step assembly of two EC units (top and side) through A-type linkages.

Total Synthesis and Structure Assignment of Saptomycin H.

We report herein the first total synthesis of saptomycin H (), by which the unidentified absolute stereochemistry of the oxiranyl side chain has been determined as 14,16. The keys include (1) concise assembly of three units, anthrone, sugar and side chain, and (2) AZADOL-mediated 6--selective pyranone (A-ring) formation.

Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins.

The number of people worldwide suffering from Alzheimer's disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively.

Intramolecular Benzyne-Phenolate [4+2] Cycloadditions.

An intramolecular benzyne-phenolate [4+2] cycloaddition is reported. Benzyne precursors, having vicinal halogen-sulfonate functionalities, linked with a phenol(ate) by various tether groups undergo efficient intramolecular [4+2] cycloaddition by treatment with either Ph MgLi or nBuLi for halogen-metal exchange to form various benzobarrelenes.

Synthesis of Enantiopure -Symmetric Anthracenophane and Dimerization En Route to Multiple-Bridged Cyclophanes.

We report the stereocontrolled synthesis of enantiopure -symmetric anthracenophanes and their derivatization to -symmetric multiple-bridged cyclophanes via photoinduced [4 + 4] dimerization.

Syntheses of doubly linked proanthocyanidins using free flavan units as nucleophiles: insight into the origin of the high regioselectivity of annulation.

A synthesis method of doubly linked flavan dimers is reported via the acid-promoted annulation reaction using nascent catechins, (+)-catechin or (-)-epicatechin, as a dianionic partner and an ethylenedioxy-bridged flavan as a dicationic partner. Procyanidins A1 and A2 were synthesized. On the high regioselectivity of the annulation reactions, model experiments and computational studies were carried out.

Stereochemical Dichotomy in Two Competing Cascade Processes: Total Syntheses of Both Enantiomers of Spiroxin A.

The first total synthesis of the marine antibiotic spiroxin A has been achieved for both enantiomeric forms. The discovery of two competing cascade processes triggered by two orthogonal stimuli, photo-irradiation or acid/base treatment, enabled the divergent conversion of a single chiral, nonracemic bis-quinone into both enantiomers of an advanced intermediate en route to both (-)- and (+)-spiroxin A. The mechanism of the enantiodivergence is discussed.

Total Synthesis of Carthamin, a Traditional Natural Red Pigment.

The first total synthesis of carthamin (3), a historic natural red pigment, has been achieved. The molecular structure was efficiently constructed by assembling two equivalents of the in situ generated lithiated monomers and triisopropyl orthoformate. This synthesis confirms the structure proposed in 1996.

Synthesis of Oxygenated -Methylbenzaldehydes Aryne [2+2] Cycloaddition and Benzocyclobutenol Ring Opening.

Herein, a two-step procedure for the preparation of oxygenated -methylbenzaldehyde derivatives, starting from commercially available bromoarenes, is described. The synthesis features the simultaneous and highly regioselective installation of both the methyl and the formyl group onto the benzene core benzyne [2+2] cycloadditions with acetaldehyde lithium enolate to give the corresponding benzocyclobutenols in high yields. Bond-selective ring opening of the benzocyclobutenols under basic conditions in methanol delivers the title compounds.

Model Reactions for the Enantioselective Synthesis of γ-Rubromycin: Stereospecific Intramolecular Photoredox Cyclization of an ortho-Quinone Ether to a Spiroacetal.

A model study for the enantioselective total synthesis of γ-rubromycin has revealed a promising approach for constructing the chiral, nonracemic bicyclic spiroacetal via the stereospecific photoredox reaction of 1,2-naphthoquinone ether.

Intramolecular photoredox reactions of 1,2-naphthoquinone derivatives.

Photoirraditation of substituted 1,2-naphthoquinones gives the corresponding oxacycle via intramolecular redox reaction, which enabled net CH functionalization of the proximal position to the excited carbonyl group of the quinones. The substrate scope and mechanistic insights are described.

Total Syntheses of Pusilatins A-C, Liverwort-Derived Macrocyclic Bisbibenzyl Dimers.

The total syntheses of pusilatins A (2), B (3), and C (5), macrocyclic bisbibenzyl dimers isolated from Japanese liverwort are reported. The common monomeric unit (6) was prepared via macrocyclization of an o-sulfinylfluorobenzene derivative by SAr attack of an internal phenol, which was exploited for site-selective dimerizations en route to 2, 3, and 5.

Total Synthesis of Selligueain A, a Sweet Flavan Trimer.

The first total synthesis of selligueain A (4), a plant-derived sweet polyphenol, has been achieved. The key step was the de novo synthetic approach to the selectively protected epiafzelechin unit 10, which was divergently converted to three flavan units 7, 8, and 9. These components were combined by an orthogonal activation and annulation method, enabling assembly of the characteristic trimeric structure with single and double interflavan linkages.

Impact of Green Tea Catechin ECG and Its Synthesized Fluorinated Analogue on Prostate Cancer Cells and Stimulated Immunocompetent Cells.

Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3--gallate only, we studied epicatechin-3--gallate, the second most abundant green tea polyphenol with essential therapeutic potential, to obtain a more detailed understanding of its anti-tumor and anti-inflammatory action.

Stereospecificity in Intramolecular Photoredox Reactions of Naphthoquinones: Enantioselective Total Synthesis of (-)-Spiroxin C.

Intramolecular photoredox reactions of naphthoquinone derivatives were found to proceed in a stereospecific manner. This method was used as a basis for the enantioselective total synthesis of (-)-spiroxin C.

Enantioselective Access to Bicyclo[3.2.1]octadienone Skeleton: Total Syntheses of (+)-Engelharquinone and Its Epoxide.

The first enantioselective total syntheses of engelharquinone (2) and its epoxide 3 have been achieved. The key steps include (1) catalytic asymmetric 1,4-addition of a naphthylboronic acid derivative to a masked naphthoquinone derivative by using a chiral Rh-complex and (2) thiolate-promoted stereospecific construction of the bicyclo[3.2.

Synthetic Study on Carthamin. 2. Stereoselective Approach to C-Glycosyl Quinochalcone via Desymmetrization.

Toward the total synthesis of carthamin, a stereoselective approach to the C-glycosyl quinochalcone intermediate is reported via the desymmetrization of a pseudo-C-symmetric C-glycosyl cyclohexadienone.

Stereocontrolled Total Syntheses of (-)-Rotenone and (-)-Dalpanol by 1,2-Rearrangement and S Ar Oxycyclizations.

The total syntheses of (-)-rotenone and (-)-dalpanol have been achieved by a group-selective, stereospecific 1,2-shift of an epoxy alcohol and S Ar cyclizations. Three oxacycles are constructed, thus illustrating a versatile synthetic route to various rotenoids.