Cyclopropanols are readily available via the Kulinkovich cyclopropanation, the Simmons-Smith reaction, and other synthetic methods. Due to their intrinsic ring stains, cyclopropanols and their ...derivatives are highly reactive and can be converted to different structural scaffolds which are frequently found in many natural products. In this review, we highlight the applications of various cyclopropanol ring opening/expansion/fragmentation reactions in the total syntheses of natural products.
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Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various β-substituted carbonyl products. Among these ring opening cross coupling ...reactions, the formation of α,β-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of α,β-unsaturated enone intermediates is actually essential for the γ-butyrolactone synthesis and also contributes to the formation of the δ-ketoester product. The γ-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated α,β-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope.
Tetrahydrofurans (THFs) and tetrahydropyrans (THPs) are important core scaffolds frequently found in many molecules of medicinal importance. Herein, we report a novel copper-catalyzed ...hydroxycyclopropanol ring-opening cyclization methodology to synthesize di- or tri-substituted THFs and THPs. In this reaction, a strained C-C bond was cleaved and a new Csp
3
-O bond was formed to produce the aforementioned O-heterocycles. The new THF synthesis features a broad substrate scope, scalability, and good functional-group tolerability. It enabled us to complete the shortest enantioselective syntheses of hyperiones A and B (3 and 4 steps, respectively), which is significantly shorter than the previously reported two total syntheses (≥10 steps).
A novel Cu-catalyzed hydroxycyclopropanol ring-opening cyclization was developed to synthesize substituted tetrahydrofuran/tetrahydropyran molecules including two norlignan natural products hyperiones A and B.
Herein, we report the total syntheses of phleghenrines A and C from commercially available starting materials in 7 and 8 steps, respectively. Notable steps include an inverse electron-demand ...Diels–Alder reaction between a masked o-benzoquinone and a N-protected enamine to prepare one key intermediate with a bicyclo2.2.2octenone core, a Büchner–Curtius–Schlotterbeck one-carbon insertion to expand the bicyclo2.2.2octenone to a bicyclo3.2.2nonenone, and Trauner’s modified 2-pyridone synthesis to install the 2-pyridone moiety.
2‐Deoxy sugars and their derivatives occur abundantly in many pharmaceutically important natural products. However, the construction of specific 2‐deoxy‐glycosidic bonds remains as a challenge. ...Herein, we report an efficient way to prepare 2‐deoxy‐α‐glycosides by glycosylation of 2‐iodo‐glycosyl acetate and subsequent visible‐light‐mediated tin‐free reductive deiodination. We have successfully applied the postglycosylational‐deiodination strategy in the synthesis of more than 30 mono‐, di‐, tri‐, tetra‐ and pentadeoxysaccharides with excellent stereoselectivity and efficiency. This method has also been applied to the synthesis of a 2‐deoxy‐tetrasaccharide containing four α‐linkages.
Fast detour: A postglycosylational‐ deiodination strategy was successfully applied in the synthesis of α‐linked 2‐deoxy glycosides. The visible‐light‐mediated reductive deiodination reaction enabled the efficient synthesis of 2‐deoxy‐α‐glycosides. The selective deiodination can be achieved in the presence of a range of functional groups (see scheme).
Protein arginine methyltransferase 5 (PRMT5) is a master epigenetic regulator and an extensively validated therapeutic target in multiple cancers. Notably, PRMT5 is the only PRMT that requires an ...obligate cofactor, methylosome protein 50 (MEP50), to function. We developed compound 17, a novel small-molecule PRMT5:MEP50 protein–protein interaction (PPI) inhibitor, after initial virtual screen hit identification and analogue refinement. Molecular docking indicated that compound 17 targets PRMT5:MEP50 PPI by displacing the MEP50 W54 burial into a hydrophobic pocket of the PRMT5 TIM barrel. In vitro analysis indicates IC50 < 500 nM for prostate and lung cancer cells with selective, specific inhibition of PRMT5:MEP50 substrate methylation and target gene expression, and RNA-seq analysis suggests that compound 17 may dysregulate TGF-β signaling. Compound 17 provides a proof of concept in targeting PRMT5:MEP50 PPI, as opposed to catalytic targeting, as a novel mechanism of action and supports further preclinical development of inhibitors in this class.
The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and ...cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia.
Urban water supply pipe network system is a huge and complicated underground project. Water supply pipe network is buried deep underground for a long time, with wide distribution, complex structure ...and various materials. The water supply pipe network serves as the lifeblood of a city. In recent years, the problems of water supply network such as dispatching, leakage and control become more and more prominent, leading to the increasing demand for water supply network management and maintenance. The late start of infrastructure construction has greatly increased the difficulty of viewing and processing pipe network information, so that the traditional manual management mode is difficult to meet the demand. In response to the issues existing in the urban water supply pipe network, we developed GIS mobile terminal system of water supply pipe network based on database technology, GIS technology and ArcGIS technology. Using the Android mobile terminal as the platform, we employ modern terminal GPS positioning system technology and 5G network communication interaction to build an efficient, reasonable and practical GIS system of water supply network. The mobile terminal system enhances the operational and supervisory capabilities of the water supply pipe network, realizes the intelligent operation of urban water supply pipe network, and improves the level of water supply pipe network management and service. The system is mainly composed of four modules, basic map operation module, map display setting module, pipe network analysis module and route navigation module. The basic map operation module links various functions through the click function to analyze distance, area and other data for users. The map display setting module uses the layer control function and GIS technology to clearly display the layers and data required by the user. The functions of the pipe network analysis module provide users with pipe network management measures. The route navigation module uses GIS positioning function to provide navigation routes for users. All four modules utilize pipe network data for statistical analysis. Users can operate the four modules on the Android mobile client platform to make the dense water supply network clearly visible. Leveraging the portable and convenient features of the mobile terminal system, relevant government departments can promptly identify accidents, coordinate personnel quickly, and formulate and implement emergency plans
In order to understand the formation of trihalomethanes (THMs) in chlorinated water and to control the production of THMs more effectively, effects of irradiation and free radical on the formation of ...THMs were observed. It was found that humic acid (HA) solution contains a semi-quinone free radical, which variation trendency was relative to the production quantity of THMs directly. Irradiating the solutions containing THMs precursor before chlorination could promote the formation of THMs, which reached the highest point at 30 minutes, after then decreased with longer irradiation time in this experimental condition. Irradiating the chlorinated solution, the yield of THMs decreased slowly because of the destruction of chlorine. The production quantity of THMs was inversely proportional to the wavelength of light sources.
An original palladium-catalyzed
ring opening carbonylative lactonization of synthetic available
hydroxycyclopropanols was reported to efficiently synthesize tetrahydrofuran
(THF) and tetrahydropyran ...(THP)-fused bicyclic γ-lactones, two unique scaffolds
often found in quite a few natural products. This new developed reaction
features mild reaction conditions, good functional group tolerability, and the
scale-up abilities. The synthetic application was demonstrated in a short total
synthesis of (±)-Paeonilide. The THF-fused bicyclic γ-lactone products can be readily
diversified into some medicinally important structures, which further broadens
the application of this new carbonylation approach.
The first total synthesis of Phleghenrine A was reported. This synthesis
features an unprecedented inverse electron-demand Diels-Alder reaction and Tiffeneau-Demjanov
ring expansion to rapidly construct bicyclo3,2,2-nonane core structure of
Phleghenrine alkaloids. Two Diels-Alder adducts were synthesized, which were
the synthetic precursors for divergent synthesis of Phleghenrine A and B,
respectively.
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