Challenges for stereoselective glycosylation of deoxy sugars are notorious in carbohydrate chemistry. We herein report a novel strategy for the construction of the less investigated β-glycosidic ...bonds of 3,5-trans-3-amino-2,3,6-trideoxy sugars (3,5-trans-3-ADSs), which constitute the core structure of several biologically important antibiotics. Current protocol leverages a C-3 axial sulfonamide group in 3,5-trans-3-ADSs as a hydrogen-bond (H-bond) donor and repurposes substoichiometric phosphine oxide as an exogenous nucleophilic reagent (exNu) to establish an intramolecular H-bond between the former and the derived α-oxyphosphonium ion. This pivotal interaction stabilizes the α-face-covered intermediate to inhibit the formation of the more reactive β-intermediate, thereby yielding reversed β-selectivity, which is unconventional for an exNu-mediated glycosylation system. A wide range of substrates was accommodated, and good to excellent β-selectivities were ensured by this H-bonding-assisted exNu effect. The robustness of the current strategy was further attested by the architectural modification of natural products and drugs containing 3,5-trans-3-ADSs, as well as the synthesis of a trisaccharide unit in avidinorubicin.
Autosomal-recessive dopa-responsive dystonia (DRD) is a rare clinical disorder presenting as bradykinesia, dystonia, tremor and even severe encephalopathy, and caused by tyrosine hydroxylase ...deficiency (THD). We report a case of compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive DRD herein.
A 16-month-old Chinese boy presented with symptoms of movement disorder and growth retardation in his infant period.
The genetic test revealed compound heterozygous mutations in the TH gene at c.457C>T and c.698G>A, which are pathogenic of DRD.
The patient was administrated low-dose levodopa.
The treatment resulted in the substantial improvement of dystonia. His long-term neurological outcome need follow-up for years.
Gene mutation analysis is helpful and necessary to diagnose DRD and has important guiding significance for the subsequent treatment.
Benzod1,3dioxoles 1,4-thiazepines remarkable antitumor activities, benzod1,3dioxoles-fused 1,4-thiazepines, which combine two biologically active heterocyclic cores, are expected to be of ...pharmacological interest, We therefore envisaged that integrating 1,4-thiazepine and benzod1,3dioxole moieties in one molecular platform could potentially produce novel compounds with significant synergistic antitumor properties. A series of novel benzod1,3dioxoles-fused 1,4-thiazepines, designed via molecular hybridization approach, were synthesized in very good yields using one-pot condensation of 3,4-methylenedioxyaniline, aldehydes, and α-mercaptocarboxylic acids under solvent-free condition. The anti-proliferative activities of all the synthesized compounds were assessed on two different human cancer cell lines (Esophageal squamous cell carcinoma Ec9706 and Eca109), and the results showed that compound 4e showed the best anti-tumor activity with IC50 values of 8.23 μM and 16.22 μM against Ec9706 and Eca109 cell lines, respectively, which was 2–3 times more potent than 5-Fluorouracil (IC50 = 23.26 μM and 30.25 μM against Ec9706 and Eca109 respectively). These novel benzod1,3dioxoles fused with bioactive heterocyclic skeletons may find their pharmaceutical applications after further investigations.
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•We designed and synthesized a series of new benzod1,3dioxoles-fused 1,4-thiazepines.•All the synthesized compounds good to potent anti-proliferative activities.•Compound 4e was found to be the most active compound.
A concise, diversity‐oriented approach for the synthesis of naturally occurring 3‐amino‐ and 3‐nitro‐2,3,6‐trideoxypyranose derivatives and analogues thereof from simple sugars has been developed. In ...addition, we investigated the synthesis of various 3‐aminoglycosyl donors and their application in glycosylation reactions. These studies led to the successful synthesis of a tetrasaccharide containing four different 3‐aminosugar components using ortho‐alkynylbenzoate donors.
A diversity‐oriented approach for the synthesis of naturally occurring 3‐amino‐ and 3‐nitro‐2,3,6‐trideoxypyranose derivatives from simple sugars has been developed. These studies led to the successful synthesis of a tetrasaccharide containing four different 3‐aminosugar components by stereoselective glycosylation of ortho‐alkynylbenzoate donors.
The Ferromagnetic Shape Memory Alloy (FSMA) Ni–Mn–Ga films have been prepared by ECR DC magnetron sputtering respectively on unheated NaCl single crystal, Cu, glass and Si wafer. It is found that the ...optimal parameters for Ni–Mn–Ga film formation are as follows: 22.5 W sputtering power, 60 mm between target and substrate, 0.1 Pa Ar
2 pressure. The films have been characterized by XRD, SEM, AFM and other techniques. There are a large number of fine grains on substrates which were formed by sputtering particles gathering. Ni–Mn–Ga film is typical nucleation growth and development. By comparison of morphology of films on different substrates, it indicates that the roughness of films is greatly affected by substrates. After heat treatment, most of the films are more uniform and compact. But the film on NaCl is broken up due to the different expansion coefficient of film and substrate. It did not occur on Cu and Si wafers. The result of X-ray diffraction indicates that the annealed films are crystalline and most orient to (022). The average crystalline grain size perpendicular to (022) lattice face crystal plane is about 8.503 nm, while its lattice deformation rate is about 1.36%. The strain of Ni–Mn–Ga film induced by magnetic field was tested. Negative 85 ppm was got when applying magnetic field about 13 koe paralleled to film surface. The standard indentation test was employed to Ni–Mn–Ga film with thickness about 400 nm. Elastic modulus of film is calculated as 3.79 GPa while hardness is 252.92 MPa.
A series of novel 1,4-naphthoquinones possessing pyrido2,3-dpyrimidine scaffolds were synthesized in very good yields using one-pot condensation of 2-hydroxy-1,4-naphthoquinone, aldehydes, and ...2-substituted 4,6-diaminopyrimidine. The in vitro anti-proliferative activity of these novel compounds was evaluated in SGC7901 and HepG2 cell lines. Almost all the tested compounds showed manifested potent inhibitory activity against the two tested cancer cell lines.
The collective total syntheses of nine natural phenylethanoid glycosides (PhEGs) together with proposed Incanoside B in a divergent mode were described. By using a core disaccharide as common ...intermediate, our developed interrupted Pummerer reaction mediated (IPRm) glycosylations adopting latent-active strategy enables the efficient, concise and divergent syntheses of these bioactive PhEGs. Among them, five natural PhEGs, Darendoside B (1), Cistanoside G (3), Decaffeoyl acteoside (4), Kankanoside F (5) and 4′′′-epi-Leonoside F (7) were the first time being synthesized. According to the synthesis of 4′′′-epi-Leonoside F (7), we also elucidated the real structure of carbohydrate component of the PhEG isolated from Rehmannia glutinosa which was misled as "Leonoside F".
A diversified synthesis of 3-aminosugar analogues of digitoxin and digoxin with potent anticancer activities was explored. The synthesis was based on a highly efficient gold-catalyzed glycosylation ...reaction with alkynylbenzoate 3-aminoglycosides as glycosyl donors. According to this strategy, a small library containing digitoxin and digoxin analogues with various 3-aminosugar scaffolds was successfully constructed.
Tetrasaccharides containing different 3‐aminosugar components have been assembled by diversity‐oriented synthesis and Yu glycosylation reactions. In their Communication on page 5227 ff., J. Zeng, Q. ...Wan, and co‐workers describe a new type of key intermediate that provides access to naturally occurring 3‐aminosugars and analogues thereof. These aminosugars were used in glycosylation reactions and should find applications in drug discovery.
Attachment of various 3-aminodeoxy sugars to natural products or drugs is a prominent method for new drug development. However, access to structurally diversified 3-aminodeoxy sugars and ...glycosylation with aglycons are challenging. We synthesized a variety of unnatural 3-aminodeoxy sugars via diversified functionalization of a common glycal intermediate bearing a cyclic sulfamidate ketimine moiety. Based on these results, the α-selective glycosylation reactions of these 3-aminodeoxy sugars and the structural modification of diosgenin were further investigated.
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