New cytotoxic natural products from the marine sponge-derived fungus Pestalotiopsis sp. by epigenetic modification

Four new polyketide derivatives, pestalotiopols A–D (1–4), together with seven known compounds (5–11), were isolated from a chemical-epigenetic culture of Pestalotiopsis sp. The structures and absolute configurations of the new compounds (1–4) were determined by spectroscopic analyses, Mo₂-induced CD, and electronic circular dichroism (ECD) calculations. All the isolated compounds (1–11) were tested for their cytotoxic activities. Among these compounds, compounds 1, 2, 6 and 7 exhibited cytotoxicity against four human cancer cell lines with IC₅₀ values of 16.5–56.5 μM. The structure–activity relationships of compounds (1–11) were examined. The results indicated that both the diol system of the side chain and the aldehyde group might contribute to the cytotoxic activity. The possible biosynthetic pathways for compounds (1–4) were also postulated.

Four new polyketide derivatives, pestalotiopols A–D (1–4), together with seven known compounds (5–11), were isolated from a chemical-epigenetic culture of Pestalotiopsis sp.     

New phenol and chromone derivatives from the endolichenic fungus Daldinia species and their antiviral activities

Three new phenolic metabolites, daldispols A–C (1–3), two new chromone derivatives, (5R,7R)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4H-chromen-4-one (9) and (5R,7R)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4H-chromen-4-one (10), together with five known phenolic compounds (4–8) and two known chromone compounds (11 and 12) were isolated from the endolichenic fungus Daldinia sp. CPCC 400770. Their structures were elucidated on the basis of spectroscopic methods, electronic circular dichroism (ECD), and comparison with reported data. Compounds 1, 3, 4, 9, and 11 exhibited significant anti-influenza A virus (IAV) activities with IC₅₀ values of 12.7, 6.4, 12.5, 16.1, and 9.0 μM, respectively, and compound 8 displayed significant anti-ZIKV activity with inhibitory ratio of 42.7% at 10 μM. The results demonstrated that the fungus Daldinia sp. CPCC 400770 might be a rich source for discovering anti-IAV secondary metabolites as potential novel leading compounds.

Eight phenols including three new ones (1–3) and four chromones including two new ones (9 and 10) were isolated from endolichenic fungus Daldinia sp. CPCC 400770, and some of them showed significant antiviral activities.     

Heptaketides from the endophytic fungus Pleosporales sp. F46 and their antifungal and cytotoxic activities

Six new heptaketides, pleosporalins A–F (1–5, and 7), and a new heptaketide derivative, pleosporalin G (9), together with four biosynthetically related known compounds (6, 8, 10, and 11), were isolated from an endophytic fungus, Pleosporales sp. F46, found in the medicinal plant Mahonia fortunei. The structures and stereochemistry of these compounds were established by extensive spectroscopic analyses including LC-HRMS, NMR spectroscopy, optical rotations, ECD calculations, and single-crystal X-ray diffraction. The antifungal activities of isolated compounds 1–11 were investigated against Candida albicans, and their cytotoxic activities were evaluated against A549, SMMC-721, and MDA-MB-231 cancer cell lines. Compound 1 was active against C. albicans with an MIC₈₀ of 128 μg mL⁻¹, and compound 7 showed moderate cytotoxicity against MDA-MB-231 with an IC₅₀ of 22.4 ± 1.1 μM. By comparing compounds 1 and 7 with structurally related metabolites, it was revealed that alterations to their C-1 or C-2 substitutions could significantly influence their antifungal or cytotoxic efficacies.

New bioactive heptaketide derivatives were isolated and characterized from an endophytic fungus, Pleosporales sp. F46.     

Dalpulapans A–E from the roots of Dalbergia stipulacea

Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb. Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb. An evaluation of cytotoxic activity against HeLa, A549 and normal cell lines using MTT assay was performed. The results showed that R,R-velucarpin A (6) was the most active against HeLa cells with an IC₅₀ value of 10.9 ± 0.42 μM, while fortunately this compound exhibited weak cytotoxicity against normal cells (29.20 ± 1.16 μM). Structures of all isolates were identified from their 1D and 2D NMR spectroscopic data and MS analysis. Experimental and calculated ECD spectra were studied to define the absolute configurations.

Five new compounds, dalpulapans A–E (1–5), were isolated from the hexane extract of the roots of Dalbergia stipulacea Roxb.     

Designing triazatruxene-based donor materials with promising photovoltaic parameters for organic solar cells

To address the increasing demand of efficient photovoltaic compounds for modern hi-tech applications, efforts have been made herein to design and explore triazatruxene-based novel donor materials with greater efficiencies. Five new molecules, namely M1–M5, were designed by structural modification of acceptor moiety (rhodanine-3-acetic acid) of well known experimentally synthesized JY05 dye (reference R), and their optoelectronic properties are evaluated to be used as donor molecules in organic solar cells. In these molecules M1–M5, triazatruxene acts as a donor unit and benzene spaced different end-capped moieties including 2-(4-(dicyanomethylene)-2-thioxothiazolidin-3-yl)acetic acid (A1), (E)-2-(4-(1-cyano-2-methoxy-2-oxoethylidene)-2-thioxothiazolidin-3-yl)acetic acid (A2), (Z)-2-(3′-ethyl-4′-oxo-2,2′-dithioxo-3′,4′-dihydro-2′H,5H-[4,5′-bithiazolylidene]-3(2H)-yl)acetic acid (A3), (Z)-2-(4′-(dicyano-methylene)-3′-ethyl-2,2′-dithioxo-3′,4′-dihydro-2′H,5H-[4,5′-bithiazol-ylidene]-3(2H)-yl)acetic acid (A4) and 2-((4Z,4′E)-4′-(1-cyano-2-methoxy-2-oxoethylidene)-3′-ethyl-2,2′-dithioxo-3′,4′-dihydro-2′H,5H-[4,5′-bithiazolylidene]-3(2H)-yl)acetic acid (A5) respectively, as acceptor units. The electronic, photophysical and photovoltaic properties of the designed molecules M1–M5 have been compared with reference molecule R. All designed molecules exhibit reduced energy gap in the region of 1.464–2.008 eV as compared to reference molecule (2.509 eV). Frontier molecular orbital (FMO) surfaces confirm the transfer of charge from donor to acceptor units. All designed molecules M1–M5 exhibited an absorption spectrum in the visible region and they were broader as compared to that of reference R. Especially, M5 with highest λ_max value 649.26 nm and lowest transition energy value 1.90 eV was accredited to the strong electron withdrawing end-capped acceptor moiety A5. The highest value of open circuit voltage (V_oc) 1.02 eV with respect to HOMO_donor–LUMO_BTP-4Cl was shown by M5 among all investigated molecules which was 0.15 V larger than reference molecule R. The designed molecule M5 is proven to be the best candidate for both electron and hole transport mobilities due to its smallest λ_e (0.0212 eV) and λ_h (0.0062 eV) values among all studied molecules.

Five new molecules (M1–M5) were designed by structural modification of acceptor moiety (rhodanine-3-acetic acid) of well-known synthesized dye JY05, and their optoelectronic properties are evaluated to be used as donor molecules in organic solar cells.     

New triterpenoid saponin glycosides from the fruit fibers of Trichosanthes cucumerina L.

Five new triterpenoid saponin glycosides, trichocucumerisides A–E (1–5), together with eleven known compounds (6–16) were isolated from Trichosanthes cucumerina fruit fibers. The structures of the new compounds were elucidated by detailed analysis of NMR and mass spectroscopic data as well as chemical reactions. The anti-inflammatory study against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells shows that compounds 7 and 9 exhibited stronger NO inhibitory activity, with IC₅₀ values of 3.0 and 2.7 μM, respectively, with comparison to positive references Celecoxib and aminoguanidine (IC₅₀ values 75.7 and 75.0 μM, respectively). Compounds 7 and 9 also possessed a greater selectivity index (SI) of approximately 3–4-fold activity than that of the positive references.

The new glycosides 1–5, together with eleven known compounds were isolated. Two compounds exhibited more potent anti-inflammatory activity than Celecoxib and aminoguanidine reference compounds.     

Effect of Bi-substitution into the A-site of multiferroic La0.8Ca0.2FeO3 on structural,electrical and dielectric properties

(La_0.8Ca_0.2)_1−xBi_xFeO₃ (x = 0.00, 0.05, 0.10, 0.15 and 0.20) (LCBFO) multiferroic compounds have been prepared by the sol–gel method and calcined at 800 °C. X-ray diffraction results have shown that all samples crystallise in the orthorhombic structure with the Pnma space group. Electrical and dielectric characterizations of the synthesized materials have been performed using complex impedance spectroscopy techniques in the frequency range from 100 Hz to 1 MHz and in a temperature range from 170 to 300 K. The ac-conductivity spectra have been analysed using Jonscher''s power law σ(ω) = σ_dc + Aω^s, where the power law exponent (s) increases with the temperature. The imaginary part of the complex impedance (Z′′) was found to be frequency dependent and shows relaxation peaks that move towards higher frequencies with the increase of the temperature. The relaxation activation energy deduced from the Z′′ vs. frequency plots was similar to the conduction activation energy obtained from the conductivity. Hence, the relaxation process and the conduction mechanism may be attributed to the same type of charge carriers. The Nyquist plots (Z′′ vs. Z′) at different temperatures revealed the appearance of two semi-circular arcs corresponding to grain and grain boundary contributions.

(La_0.8Ca_0.2)_1−xBi_xFeO₃ (x = 0.00, 0.05, 0.10, 0.15 and 0.20) (LCBFO) multiferroic compounds have been prepared by the sol–gel method and calcined at 800 °C.     

Pseudonectrins A–D,heptaketides from an endophytic fungus Nectria pseudotrichia

Four new heptaketides, pseudonectrins A–D (1–4), and four known compounds (5–8) were isolated from cultures of an endophytic fungus Nectria pseudotrichia. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1–3 and 4 were assigned by electronic circular dichroism calculations and the modified Mosher method, respectively. Compound 1–3 showed moderate cytotoxicity, with IC₅₀ values of 11.6–41.2 μM.

The new heptaketides, pseudonectrins A–D (1–4), were isolated from a plant endophyte Nectria pseudotrichia. Compounds 1–3 showed moderate cytotoxicity towards human tumor cells.     

Synthesis and characterisation of κ2-N,O-oxazoline-enolate complexes of nickel(ii): explorations in coordination chemistry and metal-mediated polymerisation

The synthesis and characterisation (UV-Vis, IR, X-ray diffraction, etc.) of a series of Ni(ii) complexes derived from both known and novel 2-acylmethyl-2-oxazolines (2a–g: i.e., (Z)-1-R-2-(4,4′-dimethyl-2′-oxazolin-2′-yl)eth-1-en-1-ol; R = –Ph, –2-furanyl, –p-NO₂-Ph, –t-Bu, –2-thiofuranyl, p-NC-Ph, –CF₃) is reported. These Ni materials (3a–g) represent the first group 10 metal complexes of this ligand class. All derivatives reported are paramagnetic (S = 1) compounds of formulae Ni(κ²-N,O-L)₂ where L represents an enolate of structure (Z)-1-R-2-(4′,4′-dimethyl-2′-oxazolin-2′-yl)eth-1-en-1-ate formed via proton loss from 2. The air- and moisture-stable metal complexes feature a less typical distorted seesaw-shaped disposition of binding atoms around the metal centre for six structurally characterised (X-ray) examples. Preliminary investigations indicate that 3a (R = –Ph) is a useful catalysts for olefin polymerisation in the presence of alkylaluminum reagents.

Novel Ni(ii) enolate complexes derived from (Z)-1-R-2-(4′,4′-dimethyl-2′-oxazolin-2′-yl)eth-1-en-1-ols are synthesised and structurally examined. The complexes display good potency as olefin polymerisation catalysts.     

3-Decalinoyltetramic acids from kiwi-associated fungus Zopfiella sp. and their antibacterial activity against Pseudomonas syringae

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp. Their structures with absolute configurations were established by extensive spectroscopic methods and single crystal X-ray diffraction. The compounds possessed rare pentacyclic systems that might derive from a polyene precursor via [4 + 2] intramolecular Diels–Alder reactions. Compounds 1, 2, and 4 showed antibacterial activity against plant pathogen Pseudomonas syringae with MIC values of 64, 32, and 64 μg mL⁻¹, respectively.

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp.     

Sarcosenones A–C,highly oxygenated pimarane diterpenoids from an endolichenic fungus Sarcosomataceae sp.

Three new highly oxygenated pimarane diterpenoids, sarcosenones A–C (1–3), and the known 9α-hydroxy-1,8(14),15-isopimaratrien-3,7,11-trione (4), were isolated from cultures of an endolichenic fungus Sarcosomataceae sp. Their structures were elucidated based on NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compound 1 showed moderate cytotoxicity against a small panel of four human tumor cell lines, with IC₅₀ values of 7.5–26.4 μM.

The new highly oxygenated pimarane diterpenoids sarcosenones A–C (1–3) were isolated from an endolichenic fungus Sarcosomataceae sp. Compound 1 showed moderate cytotoxicity towards human tumor cells.     

New bioactive cyclopeptide alkaloids with rare terminal unit from the root bark of Ziziphus cambodiana

Six new 14-membered ring cyclopeptide alkaloids, cambodines A–F (1–6), and two known compounds, frangufoline (7) and lotusanine B (8), were isolated from the root bark extract of Ziziphus cambodiana Pierre. Their structures and configurations were established based on 1D and 2D NMR, HRMS, ECD, and X-ray crystallographic data. Compounds 1 and 3 are rare 5(14)-type cyclopeptide alkaloids that possess an imidazolidin-4-one ring in the terminal unit. The cyclopeptides were tested for their in vitro antiplasmodial, antitubercular, and cytotoxic effects against three cancer cell lines. Compound 3 showed significant antiplasmodial activity against the malarial parasite Plasmodium falciparum, with an IC₅₀ value of 6.09 μM.

Six new 14-membered ring cyclopeptide alkaloids, cambodines A–F (1–6), and two known compounds, frangufoline (7) and lotusanine B (8), were isolated from the root bark extract of Ziziphus cambodiana Pierre.     

Phomretones A–F,C12 polyketides from the co-cultivation of Phoma sp. YUD17001 and Armillaria sp.

Six new C₁₂ polyketides, phomretones A–F (1–6), were isolated from the co-culture of Armillaria sp. and the endophytic fungus Phoma sp. YUD17001 associated with Gastrodia elata. Neither fungus produced these compounds when cultured alone. The structures of 1–6 were established on the basis of comprehensive spectroscopic analyses, while their absolute configurations were determined by the comparsion of experimental and calculated ECD spectra. Compounds 2–4 are diastereoisomers of each other and featured high levels of stereoisomerization and oxidation.

Co-cultivation of Phoma sp. YUD17001 with Armillaria sp. led to the production of six new C₁₂ polyketides.     

New withanolides from Physalis minima and their cytotoxicity against A375 human melanoma cells

Seven previously undescribed withanolides, namely physaminilide A–G (1–7), and two artificial withanolides (8–9), along with 10 known analogues (10–19) were isolated from Physalis minima. The structures were established by spectroscopic analysis, including NMR and electronic circular dichroism (ECD) data. Cytotoxicity of all the isolates was evaluated against A375 human melanoma cells. Compounds 2, 5, 8, 10, 11 and 15 exhibited significant cytotoxic activities with IC₅₀ values in the range of 1.2–9.4 μM.

The new withanolides physaminilide A–G (1–7), and two artificial withanolides (8–9) were isolated from Physalis minima. Compounds 2, 5 and 8 exhibited significant cytotoxicity towards human tumor cells.     

Neuroinflammatory inhibitors from Gardneria nutans Siebold & Zuccarini

Two new monoterpene indole alkaloid glycosides nutanoside A–B (1–2), two new phenolic glycoside esters nutanester A–B (6–7), together with five known compounds (3–5, 8–9) were isolated from the ethanol extract of Gardneria nutans Siebold & Zuccarini. Their structures were established on the basis of extensive spectroscopic analysis and TDDFT/ECD calculations. Compounds 1 and 2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids. Compounds 3, 4 and 6 displayed significant inhibitory effects on NO production in over-activated BV2 microglial cells, with the IC₅₀ values of 2.29, 6.36, and 8.78 μM, respectively. Compounds 1, 5, 7 could significantly inhibit the mRNA expression of inflammatory factors TNF-α and IL-6 induced by LPS in BV2 microglial cells at the effective concentration. Moreover, compound 3 exhibited stronger cytotoxicities against U87 and HCT116 cell lines than taxol with IC₅₀ values of 10.58 and 14.60 μM, respectively.

Four new compounds were isolated from G. nutans. Compounds 1–2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids.     

Sulfonic acid functionalized metal–organic framework (S-IRMOF-3): a novel catalyst for sustainable approach towards the synthesis of acrylonitriles

A sulfonic acid functionalized metal–organic framework (S-IRMOF-3) has been synthesized by dropwise addition of chlorosulfonic acid (0.5 mL) in IRMOF-3 (1 g) containing 20 mL of CHCl₃ at 0 °C under simple stirring. The catalyst was applied in Knoevenagel condensation of various aromatic and hetero-aromatic aldehydes forming acrylonitrile derivatives. The catalyst was characterized thoroughly by using FT-IR, XRD, ¹³C MAS NMR, SEM, EDX, elemental mapping, TEM, BET, NH₃-TPD and TGA/DTA techniques. The presence of characteristic bands at 1694 cm⁻¹, 1254–769 cm⁻¹ and 1033 cm⁻¹ in the FT-IR spectrum, 2θ ≃ 6.7° and 9.8° in the XRD pattern and δ = 31.79, 39.55, 129.61, 131.46 (4C, CH), 133.54, 140.07 (2C), 167.71, 171.47 ppm (2C, 2C O) in the solid state ¹³C MAS NMR spectrum confirmed the successful formation of catalyst. This new eco-friendly approach resulted in a significant improvement in the synthetic efficiency (90–96% yield), high product purity, and minimizing the production of chemical wastes without using highly toxic reagents for the synthesis of acrylonitriles with selectivity for (Z)-isomer. Steric interactions seem to have an influence on the control of the Z-configurational isomers. By performing DFT calculations, it was found that the (Z)-isomer 3a is stabilized by 1.64 kcal mol⁻¹ more than the (E)-isomer. The catalyst could be reused for five consecutive cycles without substantial loss in catalytic activity.

Sulfonic acid functionalized metal–organic framework (S-IRMOF-3) as an efficient heterogeneous catalyst has been synthesized and employed for sustainable approach towards the synthesis of acrylonitriles in high yield and shorter reaction time period.     

New α-pyrones from an endophytic fungus,Hypoxylon investiens J2

Four new α-pyrones, hypotiens A–D (1–4), were isolated from a fungal endophyte, Hypoxylon investiens J2, harbored in the medicinal plant Blumea balsamifera. Their structures were determined through detailed HRMS and NMR spectroscopic data. Compounds 1–4 are new α-pyrone derivatives containing an unusual dimethyl substitution in the highly unsaturated side chain. Their plausible biosynthetic pathway was discussed. Biological assay indicated that compounds 1–4 showed no antimicrobial, quorum sensing inhibitory, and cytotoxic activities. The specific side chain in α-pyrone derivatives 1–4 might be responsible for the weak pharmacological activities.

Four new α-pyrones, hypotiens A–D (1–4), were isolated from a fungal endophyte, Hypoxylon investiens J2, harbored in the medicinal plant Blumea balsamifera.     

Synthesis of C14–C21 acid fragments of cytochalasin Z8via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

An efficient synthesis of the C14–C21 acid fragment of cytochalasin Z₈ was accomplished in 10 steps with 14% overall yield. Boron-mediated anti-selective aldol condensation and Pd(OAc)₂–Aphos-Y-catalysed B-alkyl Suzuki–Miyaura cross-coupling were employed to construct the requisite C17 and C18 stereogenic centres and alkene subunit.

An efficient synthesis of the C14–C21 acid fragment of cytochalasin Z₈ was accomplished in 10 steps with 14% overall yield.

Cytochalasins are secondary fungal metabolites with a wide range of biological activities that target cytoskeletal processes.¹ Cytochalasins Z₇–Z₉ (1–3, Chart 1) were isolated from the marine-derived fungus Spicaria elegans, and their structures and absolute configurations were established by Zhu et al.² Cytochalasin Z₈ (2, Chart 1) is structurally related to cytochalasins Z₇ and Z₉ and features highly substituted hydroisoindol-1-one fused with a 12-membered macrolactone ring at the C-8 and C-9 positions. Cytochalasin Z₈ has been reported to exert cytotoxicity against P388 and A-549 cell lines with IC50 values of 56 and 21 μM, respectively, and therefore has significant potential in cell biology and medicine. A number of laboratories have worked towards total synthesis of the cytochalasin family and developed linear³ or convergent⁴ strategies for their total synthesis. Total synthesis of cytochalasin congeners was accomplished by the laboratories of Stork,^3a,4a Thomas,^3b,3c,3e,3f Trost,^4d Vedejs (zygosporin E),^4b,4c,4e Myers,⁵ Liu and Tang (periconiasins A–E)⁶ and Nay (periconiasin G).⁷ To the best of our knowledge, total synthesis of cytochalasin with a 12-membered macrocyclic ring has not been reported. The intriguing molecular architecture and potent biological activity of cytochalasin Z₈ prompted us to pursue its total synthesis and render it to be readily available for biological investigations.Open in a separate windowChart 1Structures of cytochalasin Z₇–Z₉.The retrosynthetic strategy is depicted in Scheme 1. Intramolecular ring-closing metathesis (RCM) strategy⁸ which is a promising tool for constructing macrolactone is often used for synthesising macrolides.⁹ We envisioned an RCM reaction at C13 and C14 positions and an esterification for assembling a 12-membered macrolactone. Thus, acid fragment 4 was required for the total synthesis of 2. Our strategy was flexible and it allowed rapid access to structural analogues. In this study, we report the synthesis of C14–C21 acid fragment 4via a highly anti-selective aldol condensation¹⁰ of aldehyde 6 with Abiko''s chiral norephedrine-derived propionate (1R,2S)-7 (ref. 11) and B-alkyl Suzuki–Miyaura cross-coupling¹² of chiral alkyl iodide 5 with (Z)-1-bromoprop-1-ene.Open in a separate windowScheme 1Retrosynthetic bond disconnections of cytochalasin Z₈ (2) yielding C14–C21 acid fragment 4 and hydroisoindol-1-one fragment.Our first task was to construct C16–C18 syn–anti stereotriad.¹³ The aldehyde functionality in 6 was expected to undergo an anti-selective aldol reaction with the (E)-boron enolate generated from Abiko''s chiral propionate 7 for installing C17–C18 anti stereochemistry according to our synthetic strategy in Scheme 1. We initially prepared crude aldehyde 6 from commercially available (S)-methyl 3-hydroxy-2-methyl propionate (Roche ester)¹⁴ by tosylation and partial ester reduction¹⁵ (Scheme 2). The unstable crude aldehyde 6, without column chromatographic purification, was immediately used with the (E)-boron enolate derived from 7 for anti-selective aldol reaction to secure the syn/anti stereotriad in 8. The key intermediate 8 was prepared in high diastereoselectivity of 98 : 2 (determined by proton nuclear magnetic resonance spectroscopy) and in the desired absolute configuration as predicted by the chiral auxiliary in 7. The influence of the stereogenic centre of aldehyde 6 on the stereochemical course of the aldol reaction was not observed. The hydroxyl group in 8 was then protected as TES ether 9 (TESOTf, 2, 6-lutidine, 98% yield). Iodide replacement of the tosylate group in 9 with LiI–THF furnished alkyl iodide 5 in 95% yield (Scheme 2).Open in a separate windowScheme 2Synthesis of alkyl iodide 6.The cross-coupling reaction of chiral alkyl iodide 5 with (Z)-1-bromoprop-1-ene was performed under the established conditions¹⁶ for the ‘9-MeO-9-BBN variant’ of the B-alkyl Suzuki–Miyaura cross-coupling reaction.^12f,17 Alkyl iodide 5 was treated with t-BuLi in the presence of 9-MeO-9-BBN in Et₂O–THF to form the corresponding borinate species which was subjected to Pd(OAc)₂–Aphos-Y-catalysed^16,18 cross-coupling reaction with (Z)-1-bromoprop-1-ene in the presence of K₃PO₄·3H₂O as the base in THF–H₂O at room temperature to furnish 11 in 15% yield along with cyclopentanol 10 and deiodinated byproduct 12 (entry 1, Scheme 3). These results suggested that the formation of 10 could be suppressed by controlling reaction temperature. The first step reaction was maintained under low temperatures for a long time before warming up. After adding t-BuLi and THF, the reaction temperature was sequentially kept at −78 °C for 30 min, at −40 °C for 30 min, at −20 °C for 30 min and at room temperature for 2 h. The newly formed borinate species was subjected to coupling reaction with (Z)-1-bromoprop-1-ene. The yield was improved to 40% (entry 3,

Cp2ZrCl2 – Et3Al reagent system in the homo-coupling of trimethylsilyl-substituted alkynes

The reaction of trimethylsilyl-substituted alkynes with 0.5 equivalents of Cp₂ZrCl₂ and 1 equivalent of Et₃Al in toluene at room temperature for 18 hours gives, after hydrolysis/deuterolysis or iodination, functionalized products of the homo-coupling of silyl-substituted alkynes in good yield. Trimethylsilyl-substituted α,ω-diynes react with the Cp₂ZrCl₂ – Et₃Al reagent system to give (1Z,2Z)-1,2-bis(iodo(trimethylsilyl)methylene)cycloalkanes after iodinolysis.

The reaction of trimethylsilyl-substituted alkynes with 0.5 equivalents of Cp₂ZrCl₂ and 1 equivalent of Et₃Al in toluene at room temperature gives products of the homo-coupling in good yield.     

Total synthesis of Palmarumycin BGs,C1 and Guignardin E

The first total synthesis of Palmarumycin BG1–3, BG5–6, C₁ and Guignardin E (1–7) were achieved by the same intermediate Palmarumycin C₂ through a N-benzyl cinchoninium chloride-catalyzed epoxidation, an organoselenium-mediated reduction, and a cerium(iii) chloride hydrate-promoted regioselective ring-opening and elimination of cyclic α,β-epoxy ketone as the key steps via6–7 step routes using 1,8-dihydroxynaphthalene (DHN) and 5-methoxytetralone as the starting materials in overall yields of 1.0–17.4%, respectively. Their structures and absolute configurations were characterized and determined by ¹H, ¹³C NMR, IR, HR-ESI-MS and X-ray diffraction data. These compounds displayed significant inhibition activities against HCT116, U87-MG, HepG2, BGC823 and PC9 cell lines.

The first total syntheses of Palmarumycin BG1–3, BG5–6, C₁ and Guignardin E were achieved. These compounds displayed significant inhibition activities against HCT116, U87-MG, HepG2, BGC823 and PC9 cell lines.