Xu Deng

Hypercohin A, a new polycyclic polyprenylated acylphloroglucinol possessing an unusual bicyclo[5.3.1]hendecane core from Hypericum cohaerens

Hypercohin A (1), an unprecedented polycyclic polyprenylated acylphloroglucinol featuring with an unusual bicyclo[5.3.1]hendecane core, was isolated from Hypericum cohaerens. Its structure and absolute configurations were elucidated by extensive NMR methods and crystal X-ray diffractions of its p-bromobenzoate ester (2).

Lycopalhine A, a novel sterically congested Lycopodium alkaloid with an unprecedented skeleton from Palhinhaea cernua

A novel sterically congested Lycopodium alkaloid named lycopalhine A (1) that possesses a fused hexacyclic (5/5/5/6/6/6) ring system comprising a 5,9-diaza-tricyclo[6.2.1.0(4,9)]undecane moiety and a tricyclo[5.2.1.0(4,8)]decane moiety was isolated from Palhinhaea cernua L. The structure and absolute configuration were determined by spectroscopic and computational methods.

Construction of Tetracyclic 3-Spirooxindole through Cross-Dehydrogenation of Pyridinium: Applications in Facile Synthesis of (±)-Corynoxine and (±)-Corynoxine B

A facile and straightforward method was developed to construct the fused tetracyclic 3-spirooxindole skeleton, which exists widely in natural products. The formation of the tetracyclic 3-spirooxindole structure was achieved through a transition-metal-free intramolecular cross-dehydrogenative coupling of pyridinium, which were formed in situ by the condensation of 3-(2-bromoethyl)indolin-2-one derivatives with 3-substituted pyridines. As examples of the application of this new methodology, two potentially medicinal natural products, (±)-corynoxine and (±)-corynoxine B, were efficiently synthesized in five scalable steps.

Terpenoids and Norlignans from Metasequoia glyptostroboides

Four new terpenoids, metaseglyptorin A (1), metasequoic acid C (2), 12α-hydroxy-8,15-isopimaradien-18-oic acid (3), and (-)-acora-2,4(14),8-trien-15-oic acid (4), and three new norlignans, metasequirins D-F (5-7), were isolated from Metasequoia glyptostroboides, together with 15 known compounds. Structures of the new compounds were determined by analysis of their spectroscopic data, and the absolute configuration of 7 was established by the modified Mosher method. All of the compounds were evaluated for cytotoxicity against five human tumor cell lines.

Copper-Catalyzed Radical Cyclization To Access 3-Hydroxypyrroloindoline: Biomimetic Synthesis of Protubonine A

An unprecedented copper-catalyzed intramolecular radical cyclization was developed for the synthesis of 3-hydroxypyrroloindoline skeletons in excellent yields. The 3-hydroxyl group was introduced by trapping the radical intermediate with molecular oxygen or TEMPO. This process represents a unique radical oxidation pathway for tryptamine/tryptophan derivatives and allows a rapid biomimetic synthesis of natural product protubonine A.

Przewalskone: a cytotoxic adduct of a danshenol type terpenoid and an icetexane diterpenoid via hetero-Diels-Alder reaction from Salvia przewalskii.

Przewalskone (1), an unprecedented adduct of two different terpenoid units via a hetero-Diels-Alder cycloaddition, was isolated from the roots of Salvia przewalskii. The structure and absolute configurations were elucidated by extensive analysis of NMR spectra and crystal X-ray diffractions. Compound 1 exhibited significant cytotoxicities against five human cancer lines in vitro (IC(50) 0.69-2.35 μM).

Copper-Mediated Dimerization to Access 3a,3a′-Bispyrrolidinoindoline: Diastereoselective Synthesis of (+)-WIN 64821 and (−)-Ditryptophenaline

A copper-mediated cyclization and dimerization of tryptamine or tryptophan was developed to generate a C2-symmetry C3(sp(3))-C3(sp(3)) bridge with two contiguous stereogenic quaternary carbons in one step. Impressively, the ratio between exo and endo cyclization products varies when different protecting groups of Nb are utilized. This dimerization reaction could be conducted in gram scale. With this dimerization method, both endocyclotryptophan (+)-WIN 64821 and exocyclotryptophan (-)-ditryptophenaline were synthesized in 5 steps.

Discovery and structure–activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: Potential impact in diabetes

The biological screening of a collection of nature occurring diterpenoids against 11β-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11β-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11β-HSD1) = 9.4 nM and selectivity index (human 11β-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11β-HSD1 were generated using docking simulations. Based on the results, the structural-activity relationships (SARs) of compounds 1b and 2 were also discussed.

Chemical constituents from the aerial parts of Musella lasiocarpa

Phytochemical investigation of the aerial parts of the monotypic plant, Musella lasiocarpa, led to the isolation of four rare bicyclic diarylheptanoids, musellarins B-E (2–5), two new phenylphenalenones, 2-methoxy-9-(3′,4′-dihydroxyphenyl)-1Hphenalen-1-one (9), 2-methoxy-9-(3′-methoxy-4′-hydroxyphenyl)-1H-phenalen-1-one (10), a new acenaphtylene derivative, trans-(1S,2S)-3-(4′-methoxyphenyl)-acenaphthene-1,2-diol (13), and two new sucrose esters, 1,2′,3′,4′,6′-O-pentaacetyl-3-O-trans-pcoumaroylsucrose (16), 1,2′,3′,4′,6′-O-pentaacetyl-3-O-cis-p-coumaroylsucrose (17), together with nine known compounds. In addition, (4E,6E)-1-(3′,4′-dihydroxyphenyl)-7-(4″-hydroxyphenyl)-hepta-4,6-dien-3-one (15) was isolated for the first time from a natural source. The structures of new compounds were elucidated by analysis of their spectroscopic data. Compounds 2, 6, 8–10, 12, and 14 were cytotoxic toward several of the human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480). Of these, the new compound 9 was the most potent one, with IC50 values of 5.8, 10.3, 6.3, 3.3, and 2.3 µM, respectively.

Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz–enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90β. At the molecular level, inactivation of HSP90 can mimic vibsanin B’s effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90β and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.