Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis

Cytochalasans (CYTs), as well as their polycyclic (pcCYTs) and polymerized (meCYTs) derivatives, constitute one of the largest families of fungal polyketide-nonribosomal peptide (PK-NRP) hybrid natural products. However, the mechanism of chemical conversion from mono-CYTs (moCYTs) to both pcCYTs and meCYTs remains unknown. Here, we show the first successful example of the reconstitution of the CYT core backbone as well as the whole pathway in a heterologous host. Importantly, we also describe the berberine bridge enzyme (BBE)-like oxidase AspoA, which uses Glu538 as a general acid biocatalyst to catalyse an unusual protonation-driven double bond isomerization reaction and acts as a switch to alter the native (for moCYTs) and nonenzymatic (for pcCYTs and meCYTs) pathways to synthesize aspochalasin family compounds. Our results present an unprecedented function of BBE-like enzymes and highly suggest that the isolated pcCYTs and meCYTs are most likely artificially derived products.

Kinetics, SOA yields and chemical composition of secondary organic aerosol from β-caryophyllene ozonolysis with and without nitrogen oxides between 213 and 313 K

β-caryophyllene (BCP) is one of the most important sesquiterpenes (SQTs) in the atmosphere, with a large potential contribution to secondary organic aerosol (SOA) formation mainly from reactions with ozone (O3) and nitrate radicals (NO3). In this work, we study the temperature dependence of the kinetics of BCP ozonolysis, SOA yields, and SOA chemical composition in the dark and in the absence and presence of nitrogen oxides including nitrate radicals (NO3). We cover a temperature range of 213 K – 313 K, representative of tropospheric conditions. The oxidized components in both gas and particle phases were characterized on a molecular level by a Chemical Ionization Mass Spectrometer equipped with a Filter Inlet for Gases and AEROsols using iodide as the reagent ion (FIGAERO-iodide-CIMS). The batch mode experiments were conducted in the 84.5 m3 aluminium simulation chamber AIDA at the Karlsruhe Institute of Technology (KIT). In the absence of nitrogen oxides, the temperature-dependent rate coefficient of the endocyclic double bond in BCP reacting with ozone between 243 – 313 K are negatively correlated with temperature, corresponding to the following Arrhenius equation: k = (1.6 ± 0.4) × 10−15 × exp((559 ± 97)/T). The SOA yields increase from 16 ± 5 % to 37 ± 11% with temperatures decreasing from 313 K to 243 K at a total organic particle mass of 10 µg m−3. The variation of the ozonolysis temperature leads to substantial impact on the abundance of individual organic molecules. In the absence of nitrogen oxides, monomers C14-15H22-24O3-7 (37.4 %), dimers C28-30H44-48O5-9 (53.7 %) and trimers C41-44H62-66O9-11 (8.6 %) are abundant in the particle phase at 213 K. At 313 K, we observed more oxidized monomers (mainly C14-15H22-24O6-9, 67.5 %) and dimers (mainly C27-29H42-44O9-11, 27.6 %), including highly oxidized molecules (HOMs, C14H22O7,9, C15H22O7,9 C15H24O7,9) which can be formed via hydrogen shift mechanisms, but no significant trimers. In presence of nitrogen oxides, the organonitrate fraction increased from 3 % at 213 K to 12 % and 49 % at 243 K and 313 K, respectively. Most of the organonitrates were monomers with C15 skeletons and only one nitrate group. Higher oxygenated organonitrates were observed at higher temperatures, with their signal-weighted O : C atomic ratio increasing from 0.41 to 0.51 from 213 K to 313 K. New dimeric and trimeric organic species without nitrogen atoms (C20, C35) were formed in presence of nitrogen oxides at 298–313 K indicating potential new reaction pathways. Overall, our results show that increasing temperatures lead to a relatively small decrease of the rate coefficient of the endocyclic double bond in BCP reacting with ozone, but to a strong decrease in SOA yields. In contrast, the formation of HOMs and organonitrates increases significantly with temperature.

Discovery of Polyoxypregnane Derivatives From Aspidopterys obcordata With Their Potential Antitumor Activity

The bioassay-guided phytochemical study of an ethnic medicinal plant Aspidopterys obcorda ta Hemsl. var. obcordata results in the isolation of eight new polyoxypregnane derivatives, named aspidatasides A–H (1–8), along with ten known analogs (9–18). The series polyoxypregnane derivatives were screened for their cytoxic activity against HL-60 cells, and compound 2 showed the highest potency with an IC50 8.03 μM. Preliminary structure–activity relationship studies displayed that the sugar chain and double bond could notably impact their biological activity.

Study on the Synthesis, Properties and Characterization of EPEG Slump Retaining Typed Polycarboxylate Superplasticizer

The ethyl glycol vinyl ether polyoxyethylene ether (EPEG) is a new type of macromonomer to synthesize polycarboxylate superplasticizer (PCE), which has higher reactivity due to the unsaturated double bond and easily to polymerization. The EPEG slump retaining typed PCE can be synthesized by free radical polymerization though EPEG, acrylic acid and hydroxyethyl acrylate (HEA). The HEA had the greatest influence on slump retaining performance. High polymerization conversion rate of EPEG typed PCE was beneficial to improve the concrete performance.

Chiron approach for the total synthesis of brevipolide M

An efficient stereoselective synthesis of brevipolide M was established in 13 linear steps and 17.8% overall yields base on chiron approach. The key steps of our synthesis involved tandem homologation / tetrahydrofuran cyclization and sequential ring-closing metathesis (RCM) / double-bond migration in one-pot processes.

Synthesis of [1,4]Oxathiepino[5,6-b]quinolines via Base-Mediated Intramolecular Hydroalkoxylation

A base-mediated intramolecular hydroalkoxylation that was used to prepare a series of seven-membered S,O-heterocycles is described. 2-Thiopropargyl-3-hydroxymethyl quinolines were prepared starting from 2-mercaptoquinoline-3-carbaldehydes, via S-propargylation and reduction of a formyl group. Interestingly, 2-mercaptopropargyl-3-hydroxymethyl quinolines were converted into the corresponding oxathiepinoquinolines in the presence of t-BuOK. It is proposed that the S-propargyl moiety, in the presence of base, is converted into its allenyl isomer; subsequent addition of a hydroxyl group to the terminal double bond yields the 3-methyl-5H-[1,4]oxathiepino[5,6-b]quinoline in good to high yield. Notably, the procedure is adaptable to the conversion of N-propargyl indole-2-methanol into the corresponding intramolecular hydroalkoxylation product.

6.1 Thiol–Ene/Yne Click Reactions: A Powerful Tool Toward Diversity-Oriented Synthesis

The clickable addition reaction between thiols and unsaturated compounds leading to the generation of (branched/linear) thioethers or (branched/linear) vinyl sulfides is known as the hydrothiolation reaction. Based upon the nature of unsaturation, i.e. double bond or triple bond, hydrothiolation reactions are classified as thiol–ene and thiol–yne click reactions, respectively. These reactions have emerged as a powerful and widely used strategy for the generation of carbon–sulfur bonds due to several associated benefits including versatile synthetic procedures, wide functional-group tolerance, high atom economy with few to no byproducts, and simple purification. The hydrothiolation reactions have numerous trapping applications in the fields of polymer chemistry, nanoengineering, pharmaceuticals, natural products, and perhaps most importantly in medicinal chemistry for the synthesis of many drugs and bioactive molecules.

Heavier group 13/15 multiple bond systems: Synthesis, Structure and Chemical Bond Activation

Heavier group 13/15 multiple bonds have been under investigation since the late 80s and to date, several examples have been published, which shows the obsoleteness of the so-called double bond...