Total Synthesis of Marine Polyketide Plakortone Q.

The total synthesis of the natural bicyclo[3.3.0]furanolactone polyketide, plakortone Q, was achieved in 24 steps from (R)-Roche ester. The main feature of this synthetic strategy is the stereoselective construction of a central tetrahydrofuran moiety with four consecutive stereoisomeric centers using the Upjohn dihydroxylation of oxiranyl-substituted alkenes and acid-mediated 5-endo-tet cyclization.

Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds.

MGB polyamide-oligonucleotide conjugates ON 1-4 with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using T m and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py4- and Py3-), which possess binding affinity for A-T base pairs, and imidazole (Im3-) and pyrrole-γ-imidazole (Py3-γ-Im3-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py4- and Py3-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im3-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.

Biomimetic total synthesis of plakortone Q via acid-mediated tandem cyclization.

Plakortone Q and plakdiepoxide are natural polyketides isolated from the marine sponge Plakortis simplex. Bicyclo[3.3.0]furanolactone compounds, including plakortone Q, are expected to exhibit a wide range of pharmacological activities. Therefore, developing a simple and versatile synthetic method to produce these compounds is an important research goal. We have achieved the first total synthesis of plakortone Q and plakdiepoxide through an efficient protecting-group-free strategy. The key transformation was an acid-mediated tandem 5-endo-tet/5-endo-tet cyclization of vicinal diepoxide to build the tetrahydrofuran-γ-lactone motif.

Total syntheses of ent-hypocoprin A and ent-hypocoprin B.

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular SN2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.

Total Synthesis of Chlorinated Oxylipin Eiseniachloride B.

Eiseniachloride B is a marine chlorinated oxylipin isolated from the brown alga Eisenia bicyclis. This natural product contains cyclopentane, chlorohydrin, and 14-membered lactone systems that incorporate five stereogenic centers. In this paper, we report on the total synthesis of structurally unique oxylipin eiseniachloride B from optically active lactol via ecklonialactone B in a linear sequence comprising 11 steps with a 12.1% overall yield.

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy.

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.

Total synthesis of squafosacin F: stereodivergent approach to mono-tetrahydrofuran acetogenins.

Annonaceous acetogenins have a wide range of potential biological activities. The development of simple and diversity-oriented approaches to their synthesis is therefore important. We have achieved the first total synthesis of squafosacin F and assigned its absolute configuration. The key steps were an acid-mediated tandem intramolecular double cyclization to build the hydroxy-flanked mono-tetrahydrofuran core and decoration with the desired functionalities of the target natural product via highly stereoselective reactions.

Formal synthesis of cis-solamin: acid-catalyzed one-step construction of 2,5-disubstituted tetrahydrofuran.

A divergent strategy has been used for the concise and efficient enantioselective formal synthesis of Annonaceous acetogenin cis-solamin. Our synthetic strategy comprises concise preparation of the diepoxyester via an 11-membered silaketal constructed by ring-closing metathesis after the dimerization of chiral epoxides, and uses an acid-catalyzed tandem intramolecular SN2-like reaction to construct the threo-cis-threo configuration of the tetrahydrofuran-diol moiety.

Total Synthesis of ent-Ascospiroketal B.

Ascospiroketal B was isolated from a marine-derived fungus as a structurally unique polyketide possessing a rare tricyclic core including 5,5-spiroketal-γ-lactone. An asymmetric total synthesis of ent-ascospiroketal B was achieved using an original synthetic route. The synthesis included the stereoselective construction of 5,5-spiroketal for ascospiroketal B and stereocontrolled construction of a quaternary asymmetric carbon by rearrangement of a trisubstituted epoxide.

Phellilane L, Sesquiterpene Metabolite of Phellinus linteus: Isolation, Structure Elucidation, and Asymmetric Total Synthesis.

A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).

Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis.

Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate.

First total synthesis of (-)-sinularianin B.

The first enantioselective total synthesis of (-)-sinularianin B, a structurally unique sesquiterpenoid isolated from the Formosan soft coral Sinularia sp., has been accomplished in 16 steps with 39.5% overall yield. Key transformations include formation of a cyclopentane possessing a tertiary hydroxy group via a tandem intermolecular-intramolecular alkylation involving a 5-endo cyclization.

Total synthesis of marine eicosanoid (-)-hybridalactone.

(-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13-membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In this paper, we report on the total synthesis of (-)-hybridalactone (1). The unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically active γ-butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9%. A key step in the synthesis of (-)-hybridalactone (1) is the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis-cyclopropane-γ-lactone derivative. This reaction provided an efficient and stereoselective access to cis-cyclopropane-γ-lactone 12. Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (-)-hybridalactone.

Total synthesis and absolute configuration of the marine norditerpenoid xestenone.

Xestenone is a marine norditerpenoid found in the northeastern Pacific sponge Xestospongia vanilla. The relative configuration of C-3 and C-7 in xestenone was determined by NOESY spectral analysis. However the relative configuration of C-12 and the absolute configuration of this compound were not determined. The authors have now achieved the total synthesis of xestenone using their developed one-pot synthesis of cyclopentane derivatives employing allyl phenyl sulfone and an epoxy iodide as a key step. The relative and absolute configurations of xestenone were thus successfully determined by this synthesis.