Water‐Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4‐Oxadiazoles

Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water‐assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4–5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five‐ and six‐membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4‐oxadiazole derivatives having a unique hybrid isoxazoline‐oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly‐like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.     

Sesterterpenes and phenolic alkenes from the Thai sponge Hyrtios erectus

Sesterterpene, erectusolide A (1), six phenolic alkenes, erectuseneols A?F (2–7) and nine known compounds, luffalactone (8), luffariolide E (9), (6E)- and (6Z)-neomanoalide 24,25-diacetates (10 and 11), 6,6-dimethylundecane-2,5,10-trione (12), threo- and erythro-cavernosines (13 and 14), (4E,6E)-dehydromanoalide (15), echinoclerodane A (16), were isolated from the marine sponge Hyrtios erectus. Compound 13 was isolated for the first time from a natural source. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The phenolic alkenes 3 and 7, the sesterterpenes 8–11 and 15, and compounds 12–14 were evaluated for cytotoxic activities against six cancer cell lines, MOLT-3, HepG2, HeLa, HuCCA-1, A549, and MDA-MB-231.     

Iodo–sesquiterpene hydroquinone and brominated indole alkaloids from the Thai sponge Smenospongia sp.

6′-Iodoaureol, an iodo–sesquiterpene hydroquinone, 6′-aureoxyaureol, a bissesquiterpene hydroquinone, and four brominated indole alkaloids 3–6 were isolated from the Thai sponge Smenospongia sp. Additionally, four known sesquiterpene hydroquinones 12–15, ten known brominated indole alkaloids 7–11, 17–18, and 20–22, ergosterol, and furospinosulin-1 were also isolated. Compound 1 is the first reported iodo–sesquiterpene hydroquinone and compounds 7–11 were isolated for the first time from natural sources. The structures were characterized by spectroscopic analyses as well as comparison with literature data. Several of these metabolites were evaluated for cytotoxic activity against seven tumor cell lines.     

Labdane diterpenes from the rhizomes of Hedychium coronarium

A new labdane diterpenoid, (E)-labda-8(17),12-dien-15,16-olide (1) together with eight known compounds, coronarin D (2), coronarin D methyl ether (3), coronarin D ethyl ether (4), isocoronarin D (5), coronarin B (6), labda-8(17),11,13-trien-15,16-olide (7), (E)-labda-8(17),12-diene-15,16-dial (8) and 16-hydroxylabda-8(17),11,13-trien-15,16-olide (9), are isolated from the rhizomes of Hedychium coronarium. Compounds 2-4, 5 and 9 are isolated as mixtures of C-15, C-14 and C-16 epimers, respectively. Their structures are determined on the basis of their spectroscopic data. The epimeric mixtures of 2 and 3 have not been reported before. Some of them were evaluated for their cytotoxicity.     

A novel tricyclic polyketide and its biosynthetic precursor azaphilone derivatives from the endophytic fungus Dothideomycete sp

Azaphilone derivatives 1 and 2 and a novel tricyclic polyketide 3, together with a known azaphilone, austdiol (4), were isolated from the endophytic fungus Dothideomycete sp., which was isolated from a Thai medicinal plant, Tiliacora triandra. Compound 3 is the first polyketide having a tricyclic 6,6,6 ring system, which is similar to that of a terpenoid skeleton. The absolute configurations of stereogenic centers in 1-3 were addressed by Mosher's method and biosynthetic analogy with a known azaphilone isolated from the same fungus. Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.     

Siamenols A-D, four new coumarins from Mammea siamensis

Further investigation of the dichloromethane extract of the twigs of Mammea siamensis led to the isolation of four novel coumarins, named siamenols A-D (1-4) together with three known xanthones. The structures of the new coumarins were elucidated by spectroscopic analysis, including 2D NMR spectroscopic data. In addition, the absolute stereochemistry of hydroxyl group of siamenol C (3) was determined to be S configuration by using modified Mosher's method.     

Nitrogenous sesquiterpenes from the Thai marine sponge Halichondria sp.

Five nitrogenous sesquiterpenes having an isonitrile [(−)-axisonitrile-3], a formamide [(+)-axamide-3, axamide-2 and (3S^*,5R^*,6R^*,9R^*)-3-formamido-1(10)-cadinene], and an amine [(−)-halichamine] functionality were isolated from the Thai marine sponge Halichondria sp., together with two steroids, ergosterol and ergosterol peroxide. (−)-Axisonitrile-3 was isolated from the natural source for the first time, while (+)-axamide-3 and (−)-halichamine were new metabolites. The structures of these compounds were elucidated on the basis of their spectroscopic data and by chemical transformations. All sesquiterpenes were tested for their cytotoxic activity against six cancer cell lines (HeLa, HuCCA-1, A549, MOLT-3, HepG2, MDA-MB231). Only (−)-axisonitrile-3 showed strong activity to the HepG2 cell line with an IC₅₀ value of 1.3 μM.