Viability of a [2 + 2 + 1] Hetero-Pauson–Khand Cycloaddition Strategy toward <i>Securinega</i> Alkaloids: Synthesis of the BCD-Ring Core of Securinine and Related Alkaloids

Preliminary results related to the development of [2 + 2 + 1]-oxa-hetero-Pauson–Khand cycloaddition strategy toward the <i>Securinega</i> alkaloids are reported. The critical tricyclic BCD-ring core was assembled in only nine linear steps from cheap 4-hydroxy-l-proline. The study provides valuable insight into the scope of a rare hetero-Pauson–Khand reaction, a powerful tool for the rapid construction of butenolide-containing natural products

A new 3,4-<i>seco</i>-cycloartane from the leaves of <i>Hopea odorata</i> Roxb.

<div><p>A new 3,4-<i>seco</i>-cycloartane, identified as (24<i>R</i>,25<i>S</i>)-dihydroxy-26-<i>O</i>-nonadecylcarbonyloxy-3,4-secocycloarta-4(28)-en-3-oic acid (<b>1</b>), has been isolated from the leaves of <i>Hopea odorata</i> Roxb. (Dipterocarpaceae), together with the rare 3,4-<i>seco</i>-cycloart-4(28),24-diene-3,26-dioic acid (<b>2</b> or abiesatrine J) and six other known compounds (<b>3</b>–<b>8</b>). Their structures were elucidated on the basis of both chemical and spectroscopic methods.</p></div

Chiroptical study and absolute configuration of securinine oxidation products

<div><p>Time-dependant density functional theory–electronic circular dichroism spectra prediction was carried out to study the absolute configuration of phyllanthidine-type derivatives <b>5</b> and <b>6</b>, derived from securinine (<b>1</b>) and its enantiomer virosecurinine (<b>2</b>), respectively. This method demonstrated to be very reliable in this alkaloid series. Thus, <b>5</b> and <b>6</b> shared the same stereochemistry as their parent precursors, confirming the retentive nature of the oxidation sequence. In addition, this study highlighted the key role of the methylene bridge (BC ring) in the chiroptical activity of these compounds. These results fully clarified the stereochemical relationships between the phyllanthidine and the securinine subgroups.</p></div

One-Step Semisynthesis of Oleacein and the Determination as a 5‑Lipoxygenase Inhibitor

The dialdehydes oleacein (<b>2</b>) and oleocanthal (<b>4</b>) are closely related to oleuropein (<b>1</b>) and ligstroside (<b>3</b>), the two latter compounds being abundant iridoids of <i>Olea europaea</i>. By exploiting oleuropein isolated from the plant leaf extract, an efficient procedure has been developed for a one-step semisynthesis of oleacein under Krapcho decarbomethoxylation conditions. Highlighted is the fact that 5-lipoxygenase is a direct target for oleacein with an inhibitory potential (IC₅₀: 2 μM) more potent than oleocanthal (<b>4</b>) and oleuropein (<b>1</b>). This enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes. Taken together, the methodology presented here offers an alternative solution to isolation or total synthesis for the procurement of oleacein, thus facilitating the further development as a potential anti-inflammatory agent

Synthesis, Antitumor Activity, and Mechanism of Action of Benzo[<i>b</i>]chromeno[6,5‑<i>g</i>][1,8]naphthyridin-7-one Analogs of Acronycine

A series of 6-methoxy-3,3,14-trimethyl-3,14-dihydro-<i>7H</i>-benzo­[<i>b</i>]­chromeno­[6,5<i>-g</i>]­[1,8]­naphthyridin-7-one (<b>4</b>), 13-aza derivatives of benzo­[<i>b</i>]­acronycine, the isomeric 5-methoxy-2,2,13-trimethyl-2,13-dihydro-<i>6H-</i>benzo­[<i>b</i>]­chromeno­[7,6<i>-g</i>]­[1,8]­naphthyridin-6-one (<b>5</b>), and related <i>cis</i>-diols mono- and diesters were designed and synthesized. Their <i>in vitro</i> and <i>in vivo</i> biological activities were evaluated. As previously observed in the acronycine series, esters were the most potent derivatives exhibiting submicromolar activities; among them monoesters are particularly active. Racemic diacetate <b>21</b> showed a strong activity against KB-3-1 cell lines and was selected for <i>in vivo</i> evaluation and proved to be active, inhibiting tumor growth by more than 80%. After separation of the two enantiomers, compounds <b>21a</b> and <b>21b</b> were also evaluated against C38 colon adenocarcinoma; their activities were found to be significantly different