Examination of the reactivity of hydroxy groups in multioxygenated cyclohexanoids: synthetic study toward cytotoxic pericosine B

The reactivity of two hydroxy groups in some multioxygenated cyclohexanoids was examined for basic study of the synthesis of the cytotoxic marine natural product pericosine B and related compounds. Differences in reactivity for O-methylation or O-acylation among substrates were observed.     

Total synthesis of (+)-pericosine B and (+)-pericosine C and their enantiomers by using the Baylis–Hillman reaction and ring-closing metathesis as key steps

A simple and divergent route for the total synthesis of pericosine B and pericosine C and their enantiomers from d-ribose by using the Baylis–Hillman reaction and ring-closing metathesis reactions as key steps has been described.     

Chemoreactive Natural Products that Afford Resistance Against Disparate Antibiotics and Toxins

Microorganisms use chemical inactivation strategies to circumvent toxicity caused by many types of antibiotics. Yet in all reported cases, this approach is limited to enzymatically facilitated mechanisms that each target narrow ranges of chemically related scaffolds. The fungus‐derived shikimate analogues, pericoxide and pericosine A, were identified as chemoreactive natural products that attenuate the antagonistic effects of several synthetic and naturally derived antifungal agents. Experimental and computational studies suggest that pericoxide and pericosine A readily react via S_N2′ mechanisms against a variety of nucleophilic substances under both in vitro aqueous and in situ co‐culture conditions. Many of the substitution products from this reaction were highly stable and exhibited diminished toxicities against environmental fungal isolates, including the Tolypocladium sp. strain that produced pericoxide and pericosine A.     

Facile carbohydrate-based stereocontrolled divergent synthesis of (+)-pericosines A and B

An isomer-divergent synthesis of naturally occurring pericosines A and B is described starting from a known D-ribose derived ene-diol in 35% and 41% overall yields respectively of which the latter is the best synthetic method reported for pericosine B. The key features of this synthesis include the stereoselective NHK vinylation of the terminal aldehyde to the versatile diolefinic chiral intermediate and elegant conversions of the same to the corresponding final products via RCM (Ring Closing Metathesis).     

Total synthesis of trans,trans-Sanguinamide B and conformational isomers

The first total synthesis of Sanguinamide B is reported, prepared via an efficient synthetic strategy. The natural product, trans,trans-Sanguinamide B (1), was generated in a thermodynamic ratio with trans,cis-Sanguinamide B (2) and cis,cis-Sanguinamide B (3). Complete conversion of the cis,cis-Sanguinamide B conformer (3) to the natural product (1) and the trans,cis- conformer (2) was achieved by heating to 170 °C. Biological evaluation indicated that the Sanguinamide B conformers disrupted the activity of a virulence determinant in P. aeruginosa.     

Total synthesis of bis-（2,3-dibromo-4,5-dihydroxyphenyl）-methane as potent PTP1B inhibitor

Protein tyrosine phosphatase 1B （PTP1B） plays an important role as a negative regulator and has been proved to be an effective target for the treatment of type 2 diabetes mellitus. Bis-（2,3-dibromo-4,5-dihydroxyphenyl）-methane 7 was first reported as a natural bromophenol with significant inhibition against PTP1B which was isolated from red algae Rhodomela conrervoides. Intrigued by its astonishing activity （IC50 = 2.4 μmol/L）, compound 7 was synthesized with the overall yield of 24% and evaluated for its PTPIB inhibitory activity compared with natural compound.     

Total Syntheses of Linear Polythiazole/Oxazole Plantazolicin A and Its Biosynthetic Precursor Plantazolicin B

Plantazolicin A, a linear decacyclic natural product, exhibits desirable selective activity against the causative agent of anthrax toxicity. The total synthesis of plantazolicin A and its biosynthetic precursor plantazolicin B was successfully achieved by an efficient, unified, and highly convergent route featuring dicyclizations to form 2,4‐concatenated oxazoles and the mild synthesis of thiazoles from natural amino acids. This report represents the first synthesis of plantazolicin B and includes the first complete characterization data for both natural products.     

First total synthesis and structure confirmation of diacetylenic polyol (+)-oploxyne B

The first total synthesis of the natural product (+)-oploxyne B is achieved. The synthesis has led to the confirmation of absolute stereochemistry of the natural product. The natural product displayed cytotoxic activity with IC₅₀ values varying from 16 to 53 μM in four cancer cell lines tested.     

Total synthesis of (±)-hibiscone B and (±)-acyl hibiscone B

The first total syntheses of the furanosesquiterpenoids hibiscone B and acyl hibiscone B are reported. The chemistry used to prepare hibiscone B solves an important challenge to the synthesis of other members of the furanosesquiterpenoid family of natural products, for which the parent molecule, hibiscone C, has shown promising biological activity.     

Total Synthesis of Fontanesine B and Its Isomer: Their Antiproliferative Activity against Human Colorectal Cancer Cells

A concise synthesis of pyrano[3,2‐e]indole alkaloid fontanesine B by a Fischer indolization is described. This key Fischer indolization starts with the pyran‐ring and alkene intact, facilitating potential synthetic applications. Furthermore, fontanesine B and its isomer were evaluated for in vitro antiproliferative activity against human colorectal cancer cells. The isomer of fontanesine B showed higher antiproliferative activity than the natural product, fontanesine B ( 2 ).     

5′位羟基异戊烯基查尔酮类天然产物的合成及其抗菌活性研究

首次合成了Bartericin A (1), 2’,6’-二羟基-5’-(2’’-羟基-3’’-甲基-3’’-丁烯基)-4’-甲氧基查尔酮(2), Xanthohumol D (3)和Angusticornin B (4) 4个羟基异戊烯基查尔酮类天然产物.为了探讨天然产物中不同官能团对其核心骨架结构抗菌活性的影响,设计合成了衍生物6.所合成的目标产物和未知中间体化合物经过1H NMR、13C NMR、IR、HRMS进行了确证.选取大肠杆菌[CMCC(B)44102]、绿脓杆菌[CMCC(B)10104]、金黄色葡萄球菌[CMCC(B)260003]和枯草芽孢杆菌[CMCC(B)63 501],采用稀释点样法对所合成的4个天然产物及1个新型衍生物进行了抗菌活性评估.结果显示,天然产物1、4和衍生物6对革兰氏阳性菌金黄色葡萄球菌和枯草芽孢杆菌表现出了一定的抑制活性.天然产物3对枯草芽孢杆菌表现出了较为明显的抑制活性,但对其他3种菌株无抑制活性(最小抑菌浓度>200μg/mL).     

Synthesis of (+/-)-hamigeran B, (-)-hamigeran B, and (+/-)-1-epi-hamigeran B: use of bulky silyl groups to protect a benzylic carbon-oxygen bond from hydrogenolysis

Enone 42 was converted into diene 56, which was then subjected to hydrogenation. Use of the tert-butyldimethylsiloxy groups enforces facial selectivity and protects the C(5) oxygen from hydrogenolysis. The resulting product (55) is easily converted into hamigeran B (1), a marine natural product with powerful activity against herpes and polio viruses. Optically pure enone 73 was made by use of a Meyers' auxiliary and converted into (-)-hamigeran B with the natural absolute configuration.     

Anti-neuraminidase activity of chemical constituents of Balanophora involucrata

Balanophora involucrata J. D. Hooker has been known to possess potential anti-inflammatory and antibacterial activities; however, its antiviral activity has not been evaluated so far. In order to find new neuraminidase inhibitors (NAIs), the neuraminidase (NA) inhibition activity of different B. involucrata extracts was evaluated. In this study, an in vitro NA inhibition assay was performed to identify which extract of B. involucrata exhibits (maximal) inhibitory activity against NA. Ultra high performance liquid chromatography/quadrupole time-of-flight–tandem mass spectroscopy (MS/MS) and molecular docking techniques were used to identify the specific compounds responsible for the anti-influenza activity of the extract, and to explore the potential natural NAIs. The ethyl acetate extract of B. involucrata exhibited significant inhibitory activity against NA with 50% inhibitory concentration (IC₅₀) value of 159.5 μg/mL. Twenty compounds were identified according to the MS/MS spectra; among them two compounds (quercitrin and phloridzin) showed obvious inhibitory activity against NA, with IC₅₀ of 311.76 and 347.32 μmol/L, respectively. This study suggested that B. involucrata can be a potential natural source of NAIs and may be useful in the fight against ferocious influenza viruses.     

Syntheses of amamistatin fragments and determination of their HDAC and antitumor activity

[reaction: see text] Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC50 0.24-0.56 microM). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells.     

Synthesis and antiviral activities of synthetic glutarimide derivatives

A series of novel glutarimide compounds were synthesized and their antiviral activities were evaluated. The compounds displaying the strongest antiviral activities included 5, 6f, 7e and 9 against coxsackievirus B3 (Cox B3), 10 and 6f against influenza virus A (influenza A) and 7a against herpes simplex virus 2 (HSV-2). However, most of the synthetic glutarimides showed comparatively much weaker activity against influenza A, Cox B3 and HSV-2 than the natural glutarimide compounds tested. Based on the results, it seemed likely that a conjugated system at the β-substituted moiety provides stronger antiviral activity.     

Total synthesis of spiruchostatin B aided by an automated synthesizer

The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs.     

A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.     

Total syntheses of (+)- and (-)-cacospongionolide B: new insight into structural requirements for phospholipase A(2) inhibition

The first total synthesis of the antiinflammatory marine sponge metabolite (+)-cacospongionolide B has been accomplished in 12 linear steps. The pivotal transformations include a three-step sequence coupling the two main regions of the natural product as well as generating the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A(2) suggests that cacospongionolide B has an enantiospecific interaction with the enzyme that is independent of the gamma-hydroxybutenolide moiety.