Novel One-pot Three-component Coupling Reaction with Trimethylsilylmethyl-phosphonate, Acyl Fluoride, and Aldehyde through the Horner–Wadsworth–Emmons Reaction

A novel three-component coupling between trimethylsilylmethylphosphonate, acyl fluoride, and aldehyde has been developed. A sequential nucleophilic addition of lithio-trimethylsilylmethylphosphonate to the acyl fluoride and Horner–Wadsworth–Emmons reaction of an aldehyde with the lithio-<b>β</b>-ketophosphonate generated in situ by desilylation at the α-position of the α-silyl-β-ketophosphonate by fluoride took place cleanly in a one-pot operation. Various <i>E</i>- and <i>Z</i>-enones were obtained in high yields with high stereoselectivities by this one-pot procedure

Confirmation of the Configuration of 10-Isothiocyanato-4-cadinene Diastereomers through Synthesis

The marine sponge metabolite 10-isothiocyanato-4-cadinene (<b>1</b>) was first isolated by Garson et al. from <i>Acanthella cavernosa</i> in 2000. The same structure <b>1</b> was later reported by Wright et al. from the nudibranch <i>Phyllidiella pustulosa</i> and its sponge diet, but with different NMR data. The syntheses of both enantiomers of <b>1</b> were accomplished through the isothiocyanation of 10-isocyano-4-cadinene (<b>2</b>) previously synthesized by our group. The correct spectroscopic data and specific rotation value of the structure <b>1</b> were determined on the basis of the syntheses. The NMR data of synthetic <b>1</b> matched those of the isothiocyanate isolated by Garson and differed from those reported by Wright. The spectroscopic data and specific rotation values of 10-<i>epi</i>-10-isothiocyanato-4-cadinene (<b>6</b>) and di-1,6-<i>epi</i>-10-isothiocyanato-4-cadinene (<b>8</b>) were also established through the syntheses of these diastereomers. Structure <b>6</b> has been reported as a natural product by Mitome et al., but the NMR data for the synthetic sample of <b>6</b> differ from those of the natural isolate

Synthesis and Biological Activity of Kalkitoxin and its Analogues

Total syntheses of kalkitoxin, isolated from the Caribbean <i>Lyngbya majuscula</i>, and its analogues, 3-<i>epi</i>-, 7-<i>epi</i>-, 8-<i>epi</i>-, 10-<i>epi</i>-, 10-<i>nor</i>-, and 16-<i>nor</i>-kalkitoxin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient TiCl₄-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp

Columbamides D and E: Chlorinated Fatty Acid Amides from the Marine Cyanobacterium Moorea bouillonii Collected in Malaysia

Two new chlorinated fatty acid amides, columbamides D (<b>1</b>) and E (<b>2</b>), along with apratoxins A and C and wewakazole, were isolated from the organic extract of a Moorea bouillonii sample from Sabah, Malaysia. Structure elucidation was accomplished by a combination of MS and NMR analyses. The total synthesis of all four stereoisomers of <b>1</b> was completed, and the absolute configuration was determined by chiral-phase HPLC and Marfey’s analysis

Thrombin Inhibitors from the Freshwater Cyanobacterium <i>Anabaena compacta</i>

Bioassay-guided investigation of the cyanobacterium <i>Anabaena compacta</i> extracts afforded spumigin J (<b>1</b>) and the known thrombin inhibitor spumigin A (<b>2</b>). The absolute configuration of <b>1</b> was analyzed by advanced Marfey’s methodology. Compounds <b>1</b> and <b>2</b> inhibited thrombin with EC₅₀ values of 4.9 and 2.1 μM, and 0.7 and 0.2 μM in the cathepsin B inhibitory assay, respectively. The MM-GBSA methodology predicted spumigin A with 2<i>S</i>-4-methylproline as the better thrombin inhibitor

Serinolamides and Lyngbyabellins from an <i>Okeania</i> sp. Cyanobacterium Collected from the Red Sea

NMR- and MS-guided fractionation of an extract of an <i>Okeania</i> sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (<b>1</b>) and D (<b>2</b>) and lyngbyabellins O (<b>3</b>) and P (<b>4</b>), together with the three known substances lyngbyabellins F (<b>5</b>) and G (<b>6</b>) and dolastatin 16 (<b>7</b>). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of <b>1</b> and <b>2</b> were determined by Marfey’s analysis of their hydrolysates. The absolute configuration of <b>3</b> was ascertained by chiral-phase chromatography of degradation products, while that of <b>4</b> was determined by comparison to <b>3</b> and <b>5</b>. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and <i>Amphibalanus amphitrite</i> larvae, respectively. Compounds <b>3</b>, <b>4</b>, and <b>7</b> exhibited strong antifouling activity, and <b>3</b> and <b>7</b> were not cytotoxic. A structure–activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (<b>4</b> is more active than <b>3</b>) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (<b>3</b>) was the most active