Enantioselective and collective total synthesis of pentacyclic 19-nor-clerodanes.

We report herein the collective asymmetric total synthesis of seven pentacyclic 19-nor-clerodane diterpenoids, namely (+)-teucvin (+)-cracroson A, (+)-cracroson E, (+)-montanin A, (+)-teucvisin C, (+)-teucrin A, and (+)-2-hydroxyteuscorolide. An ytterbium-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of 4-methyl-2-pyrone with a chiral C5-substituted cyclohexa-1,3-dienol silyl ether is the key feature of the synthesis, which provides the common cis-decalin intermediate with five continuous stereocenters in excellent yield and stereoselectivity. From this diversifiable intermediate, the total synthesis of (+)-teucvin and (+)-2-hydroxyteuscorolide was realized in thirteen and eighteen steps, respectively. From (+)-teucvin, five other pentacyclic 19-nor-clerodanes were divergently and concisely generated through late-stage oxidation state adjustments.

Catalytic Asymmetric Inverse-Electron-Demand Diels-Alder Reactions of 2-Pyrones with Indenes: Total Syntheses of Cephanolides†A and B.

An inverse-electron-demand Diels-Alder (IEDDA) reaction could complement the conventional normal-electron-demand Diels-Alder reaction in the synthesis of six-membered carbocycles. However, catalytic asymmetric all-carbon-based IEDDA reactions are underdeveloped. Herein, we disclosed a copper-catalyzed asymmetric IEDDA reaction using electron-deficient 3-carboalkoxyl-2-pyrones and electronically unbiased indenes as reactants. This method enables the rapid and enantioselective construction of a wide range of hexahydrofluorenyl bridged-lactone scaffolds. Using this method, asymmetric total syntheses of cephanolides A and B were accomplished.

Enantioselective Synthesis of cis-Decalin Derivatives by the Inverse-Electron-Demand Diels-Alder Reaction of 2-Pyrones.

A novel strategy for the synthesis of cis-decalins by an ytterbium-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones and silyl cyclohexadienol ethers is reported here. A broad range of synthetically important cis-decalin derivatives with multiple contiguous stereogenic centers and functionalities are obtained in good yields and stereoselectivities. A full set of diastereomeric substituted cis-decalin motifs are readily accessible by tuning the absolute configurations of substituted silyl cyclohexadienol ethers (R or S) as well as the ligands (R or S). The synthetic potential is showcased by the enantioselective total synthesis of 4-amorphen-11-ol, and further demonstrated by the first total synthesis of cis-crotonin.

Enantioselective Synthesis of Arene cis-Dihydrodiols from 2-Pyrones.

An enantioselective chemical synthesis of arene cis-dihydrodiols has been realized from 2-pyrones through sequential ytterbium-catalyzed asymmetric inverse-electron-demand Diels-Alder (IEDDA) reaction of 2-pyrones and retro-Diels-Alder extrusion of CO2 . By using this strategy, a series of substituted arene cis-dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)-MK7607 and 1-epi-(+)-MK7607 were accomplished.

Effect and Mechanism of Active Fraction of Polyrhachis vicina in Treatment of Systemic Lupus Erythematosus(SLE) / 中国实验方剂学杂志

Objective: To observe the effect of an active fraction of Polyrhachis vicina (AFPV) on systemic lupus erythematosus (SLE) and its possible mechanism based on animal and cell models. Method: Totally 60 SD rats were randomly divided into normal control group, model group, prednisone acetate group (5 mg·kg-1), and high, medium and low-dose AFPV groups (400, 200, 100 mg·kg-1). SLE model was replicated with bovine serum albumin-Freund's complete (incomplete) adjuvant. Arthus reaction was observed to study the effect of AFPV on the diameter of back skin redness in rats with SLE. The expressions of anti-double-stranded DNA (dsDNA) antibody, complements 3 (C3), complement 4 (C4), immunoglobulin M (IgM), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-31 (IL-31) and interleukin-33 (IL-33) in serum were detected by enzyme-linked immunosorbent assay. CD4+T cells were isolated from the spleens of MRL/lpr and C57BL/6J mice at the age of 16 to 18 weeks by immunomagnetic beads method. The expressions of miR-200a and miR-155 and the levels of zinc-finger-enhancer binding protein 1(ZEB1) and suppressor of cytokine signaling1(SOCS1) in CD4+T cells were observed to explore the effect of AFPV on SLE and its possible mechanism. Result: Compared with the normal group, the diameter of back skin swelling in the model group was significantly increased (PPPPPPP+T cells of MRL/lpr lupus mice. Compared with the model group, the expression of microRNA-200a increased significantly, the expression of microRNA-155 decreased significantly (PPConclusion: AFPV has therapeutic effect on rats with SLE, its mechanism may be related to the regulation of miR-200a/ZEB1 and miR-155/SOCS1.