Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach.

Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.

[Studies on chemical constituents of Serissa serissoides roots].

OBJECTIVE: To study the chemical constituents from Serissa serissoides DC. roots. METHODS: Seven compounds were obtained from the 80% ethanol extract of Serissa serissoides roots by repeated column chromatography over silica gel, Sephadex LH-20 and Polyamide. Their structures were identified by analysis of their spectral data and physics character. RESULTS: Seven compounds obtained from the plant leaves were identified as: (+)-pinoresinol(1), (-)-syringaresinol( 2), (+)-meduiresinol(3), (-)-olivil(4), beta-sitosterol(5), oleanolic acid(6) and daucosterol(7). CONCLUSION: They are all known compounds. Compound 2 and 4 was obtained from this genus plants for the first time, and compounds 1,3 and 7 as known compounds were obtained from the root of the plant firstly.

Two new alkaloids from the rhizome of Polygonatum sibiricum.

Two new alkaloids named polygonatine A (1) and polygonatine B (2) have been isolated from the rhizome of Polygonatum sibiricum Redoute (Liliaceae). By spectral data (IR, UV, MS, 1D and 2D NMR) and chemical evidence, their structures were elucidated as 3-hydroxymethyl-5,6,7,8-tetrahydroindolizin-8-one (1) and 3-ethoxymethyl-5,6,7,8-tetrahydroindolizin-8-one (2).

Absolute configuration determination of angular dihydrocoumarins from Peucedanum praeruptorum.

From Peucedanum praeruptorum, one new khellactone ester (3'R)-O-acetyl-(4'S)-O-angeloylkhellactone (3), as well as four known angular dihydropyranocoumarins (1, 2, 4, 5) have been isolated. On the basis of NMR spectra and X-ray crystallography, their structures were determined. We have elucidated their absolute configuration by either chiral separation of their alkaline hydrolysis products with Rp-18 HPLC eluted with 5% hydroxypropyl-beta-cyclodextrin (beta-HCD) or by measurement of their CD spectra. A general rule relating the position and absolute streochemistry of the khellactone esters to the sign of their Cotton effects in CD curves is proposed.