Total Synthesis of (−)-L-755,807: Establishment of Relative and Absolute Configurations

The first total synthesis of (−)-L-755,807 and its three stereoisomers was achieved by our Horner–Wadsworth–Emmons reaction for stereoselective formation of trisubstituted olefins, highly diastereoselective Darzens condensation to construct the epoxy-γ-lactam ring, and late-stage coupling of the ring and side-chain segments for efficient convergent synthesis. This synthesis shows that the originally proposed structure of natural (−)-L-755,807 was incorrect and establishes its relative and absolute configurations

A Unified Route to the Welwitindolinone Alkaloids: Total Syntheses of (−)-<i>N</i>-Methylwelwitindolinone C Isothiocyanate, (−)-<i>N</i>-Methylwelwitindolinone C Isonitrile, and (−)-3-Hydroxy-<i>N</i>-methylwelwitindolinone C Isothiocyanate

As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]­decane core, we report herein concise asymmetric total syntheses of (−)-<i>N</i>-methylwelwitindolinone C isothiocyanate (<b>2a</b>), (−)-<i>N</i>-methylwelwitindolinone C isonitrile (<b>2b</b>), and (−)-3-hydroxy-<i>N</i>-methylwelwitindolinone C isothiocyanate (<b>3a</b>) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of <b>2a</b> provided access to <b>2b</b> and <b>3a</b>, respectively. Notably, this work provides corrected ¹H and ¹³C NMR spectral data for <b>3a</b>

A Unified Route to the Welwitindolinone Alkaloids: Total Syntheses of (−)-<i>N</i>-Methylwelwitindolinone C Isothiocyanate, (−)-<i>N</i>-Methylwelwitindolinone C Isonitrile, and (−)-3-Hydroxy-<i>N</i>-methylwelwitindolinone C Isothiocyanate

As part of a comprehensive strategy to the welwitindolinone alkaloids possessing a bicyclo[4.3.1]­decane core, we report herein concise asymmetric total syntheses of (−)-<i>N</i>-methylwelwitindolinone C isothiocyanate (<b>2a</b>), (−)-<i>N</i>-methylwelwitindolinone C isonitrile (<b>2b</b>), and (−)-3-hydroxy-<i>N</i>-methylwelwitindolinone C isothiocyanate (<b>3a</b>) from a common tetracyclic intermediate. The crucial vinyl chloride moiety was installed through electrophilic chlorination of a hydrazone, but only after adjustment of reactivity to circumvent a facile skeletal rearrangement. Selective desulfurization and oxidation of <b>2a</b> provided access to <b>2b</b> and <b>3a</b>, respectively. Notably, this work provides corrected ¹H and ¹³C NMR spectral data for <b>3a</b>

Establishment of Relative and Absolute Configurations of Phaeosphaeride A: Total Synthesis of <i>ent</i>-Phaeosphaeride A

The relative and absolute configurations of phaeosphaeride A have been established via the first total synthesis of <i>ent</i>-phaeosphaeride A. The three contiguous stereogenic centers were installed by Sharpless asymmetric dihydroxylation and a stereoselective intramolecular vinyl anion aldol reaction. This synthesis has altered the originally proposed structure of natural phaeosphaeride A

Location of sample sites.

<p>Location of sample sites.</p

Summed Probability Distribution (SPD) of the three regions (solid line).

<p>The thick lines show the 200-years rolling mean, whilst the grey band represents the 95% confidence interval for the null model (upper row: uniform distribution; lower row: exponential distribution). Red and blue vertical bands represent intervals with significant positive and negative deviations.</p

Significance levels of the global statistics for the null model and the pair-wise permutation tests (values in bold are significant at 0.01, values in italic at 0.1.

<p>Significance levels of the global statistics for the null model and the pair-wise permutation tests (values in bold are significant at 0.01, values in italic at 0.1.</p

Comparison of the three SPDs.

<p>Each row represents an observed SPD of a region compared against another in the column. Red and blue vertical bands represent intervals with significant positive and negative deviations from a null model of the aggregated set of each of pair. The x-axes are in cal BP.</p

Design, Synthesis, and Biological Evaluations of Aplyronine A–Mycalolide B Hybrid Compound

A hybrid compound consisting of aplyronine A and mycalolide B was synthesized, and its biological activities were evaluated. The hybrid compound was found to have somewhat more potent actin-depolymerizing activity than aplyronine A. In contrast, the hybrid compound possessed about 1000-fold less cytotoxicity than aplyronine A. These results indicated that there is no direct correlation between actin-depolymerizing activity and cytotoxicity

Total Synthesis of Highly Oxygenated Bisabolane Sesquiterpene Isolated from <i>Ligularia lankongensis</i>: Relative and Absolute Configurations of the Natural Product

The relative and absolute configurations of an oxygenated bisabolane natural product, isolated from <i>Ligularia lankongensis</i>, were determined by synthesis. All four possible stereoisomers and their tiglate analogues were synthesized from <i>R</i>-(−)-carvone, and their ¹H and ¹³C NMR spectra were compared to establish the 6<i>R</i>,8<i>S</i>,10<i>S</i> configuration. The stereoselective synthesis of the natural product was also achieved, featuring Brown allylation, vanadium-catalyzed epoxidation, and the Mitsunobu reaction