A highly efficient chemoenzymatic approach toward glycoprotein synthesis

[reaction: see text] A highly efficient endoglycosidase-catalyzed synthesis of homogeneous glycoproteins is described. By using ribonuclease B as a model system, it was demonstrated that Endo-A could efficiently attach a preassembled oligosaccharide to a GlcNAc-containing protein in a regio- and stereospecific manner, when the corresponding sugar oxazoline was used as the donor substrate. The method allows the synthesis of both natural and tailor-made N-linked glycoproteins in excellent yield.     

Bio-templated synthesis of highly ordered macro-mesoporous silica material for sustained drug delivery

The bimodal porous structured silica materials consisting of macropores with the diameter of 5–20 μm and framework-like mesopores with the diameter of 4.7–6.0 nm were prepared using natural Manchurian ash and mango linin as macropored hard templates and P123 as mesopore soft templates, respectively. The macroporous structures of Manchurian ash and mango linin were replicated with the walls containing highly ordered mesoporous silica as well. As-synthesized dual porous silica was characterized by scanning electron microscope (SEM), powder X-ray diffraction (XRD), transmission electron microscope (TEM) and nitrogen adsorption/desorption, fourier transform IR (FTIR) spectroscopy, and thermo-gravimetric analyzer (TGA). Ibuprofen (Ibu) was employed as a model drug and the release profiles showed that the dual porous material had a sustained drug delivery capability. And such highly ordered dual pore silica materials may have potential applications for bimolecular adsorption/separation and tissue repairing.     

Concise and highly efficient approach to three key pyrimidine precursors for rosuvastatin synthesis

We report the synthesis of 5-formyl-, 5-(hydroxymethyl)-, and 5-(bromomethyl) substituted N-[4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide. The presented synthetic approach is based on highly efficient three step preparation of functionalized 5-methylpyrimidine. The methyl group is selectively brominated by NBS with irradiation into the bromomethyl derivative, which is then transformed into the hydroxymethyl or formyl groups in nearly quantitative yields. This approach is superior to the existing methodologies for the preparation of the key pyrimidine precursors used in the synthesis of rosuvastatin since no metal catalysis and no cryogenic reaction conditions are involved.     

A simple and efficient approach to the synthesis of highly functionalized fused benzochromenes

Protonation of the reactive intermediates produced in the reaction between tert-butyl isocyanide and dimethyl acetylenedicarboxylate or dibenzoylacetylene, by 1-naphthol, 2-naphthol, 2,3-dihydroxynaphthalene, 2,7-dihydroxynaphthalene or 4-methyl-8-hydroxycoumarin leads to vinylnitrilium cations, which undergo carbon-centered Michael type addition with the conjugate base of the naphthols to produce highly functionalized benzochromenes.     

Modeling of highly efficient drug delivery system induced by self-assembly of nanocarriers: A density functional study

Owing to the importance of drug delivery in cancer or other diseases’ therapy, the targeted drug delivery (TDD) system has been attracting enormous interest. Herein, we model the TDD system and design a novel rod-like nanocarrier by using the coarse grained model-based density functional theory, which combines a modified fundamental measure theory for the excluded-volume effects, Wertheim’s first-order thermodynamics perturbation theory for the chain connectivity and the mean field approximation for van der Waals attraction. For comparison, the monomer nanocarrier TDD system and the no nanocarrier one are also investigated. The results indicate that the drug delivery capacity of rod-like nanocarriers is about 62 times that of the no nanocarrier one, and about 6 times that of the monomer nanocarriers. The reason is that the rod-like nanocarriers would self-assemble into the smectic phase perpendicular to the membrane surface. It is the self-assembly of the rod-like nanocarriers that yields the driving force for the targeted delivery of drugs inside the cell membrane. By contrast, the conventional monomer nanocarrier drug delivery system lacks the driving force to deliver the drugs into the cell membrane. In short, the novel rod-like nanocarrier TDD system may improve the drug delivery efficiency. Although the model in this work is simple, it is expected that the system may provide a new perspective for cancer targeted therapy.     

Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery

Efficient delivery of therapeutics into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to drug resistance and inefficient cellular uptake. Herein, we have designed a tailor-made dual pH-sensitive polymer-drug conjugate nanoparticulate system to overcome the challenges. The nanoparticle is capable of reversing its surface charge from negative to positive at tumor extracellular pH (～6.8) to facilitate cell internalization. Subsequently, the significantly increased acidity in subcellular compartments such as the endosome (～5.0) further promotes doxorubicin release from the endocytosed drug carriers. This dual pH-sensitive nanoparticle has showed enhanced cytotoxicity in drug-resistant cancer stem cells, indicating its great potential for cancer therapy.     

Solid-phase synthesis of oxaliplatin-TAT peptide bioconjugates

Platinum-based drugs play a crucial role in the fight against cancer. Oxaliplatin, which is used in the treatment of colorectal carcinoma, was the last platinum-based agent to be approved worldwide. However, the efficiency of the therapy is limited for example by a low accumulation of the drug in cancer cells. Cell-penetrating peptides (CPPs) are known to ease the cellular membrane transport and are used as vectors for low-molecular-weight drugs and drug carriers; of them, TAT peptides are the best-studied group. In this work, a TAT-peptide fragment (YGRKKRRQRRR) was for the first time conjugated to a platinum(IV) analog of oxaliplatin as a vehicle for membrane penetration. Solid-phase peptide synthesis and subsequent coupling with the platinum complex afforded mono- and difunctionalized conjugates, which were separated by preparative HPLC and characterized by analytical HPLC, ESI-MS, and (1)H NMR spectroscopy. Both conjugates are active in the low micromolar range in CH1 and SW480 human cancer cells, requiring much lower concentrations than the untargeted analogs for equal effects.     

A straightforward highly efficient Paal-Knorr synthesis of pyrroles

A straightforward simple synthesis of substituted pyrroles using bismuth nitrate-catalyzed modified Paal-Knorr method has been accomplished with an excellent yield. This method produces pyrroles with multicyclic aromatic amines.     

A novel and highly efficient synthesis of gem-difluorocyclopropanes

[reaction: see text] A new and highly versatile source of difluorocarbene is reported. Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) undergoes decomposition in the presence of catalytic fluoride to form difluorocarbene under conditions that allow its addition to relatively electron deficient alkenes in high yield. For example, unprecedented CF2: addition to n-butyl acrylate proceeded in 73% yield.     

A new and highly efficient synthesis of hydroxyporphyrins

A new synthesis of hydroxyporphyrins is reported. The method involves nucleophilic displacement of a nitro group using the sodium salt of E-benzaldoxime and is a general process allowing the synthesis of both β-hydroxyporphyrins and meso-hydroxyporphyrins. Activation of the porphyrin system towards nucleophilic attack is achieved by complexation of the macrocycle with the relatively electronegative nickel(II) or copper(II) ions. Thus, treatment of either the copper(II) or the nickel(II) chelates of 2-nitro-5, 10,15,20-tetraphenylporphyrin with the sodium salt of E-benzaldoxime gave the corresponding 2-hydroxyporphyrin in high yield. Similar treatment of the copper(II) or the nickel(II) chelates of 5-nitro-2, 3,7,8,12,13,17,18-octaethylporphyrin gave the corresponding 5-hydroxyporphyrin, again in high yield. These reactions show that metallo-nitroporphyrins display similar electrophilic properties to much simpler nitro-arene systems. The nickel(II) 5-hydroxyporphyrin 10 was cleanly demetallated on treatment with concentrated sulfuric acid to give the corresponding free-base oxophlorin thereby greatly increasing the general utility of the hydroxylation methodology. Conversion of (5-methoxy-15-nitro-2,3,7,8,12,13,17,18-octaethylporphyrinato) nickel(II) 16 into (5-acetoxy-15-methoxy-2,3,7,8,12,13,17,18-octaethyl-porphyrinato) nickel(II) 18 established that the reaction mechanism involves regiospecific replacement (i.e., ipso-substitution) of the nitro group by the oxygen nucleophile.     

A highly efficient general synthesis of phosphine-borane complexes

A general synthesis of phosphine-borane complexes proceeding in high yield in a safe, green process from borane generated in situ from sodium borohydride is described. The procedure also allows simultaneous carbonyl reduction and phosphine-borane formation on air-sensitive bulky phosphine derivatives.     

An efficient synthesis of highly functionalized chiral lactams

A new method was developed to synthesize highly functionalized lactams via a one pot reductive amination/lactam formation reaction. This methodology is amenable for parallel synthesis and was used to prepare a large number of lactam analogs in a library format with good ee (de) retention.     

Electrochemical synthesis of sulfur-doped graphene sheets for highly efficient oxygen reduction

Sulfur(S)-doped graphene sheets were prepared by a facile electrochemical method, which effectively combined exfoliation of graphite and in situ S doping of graphene together. The metal-free S-doped graphene sheets exhibit high electrocatalytic activity, long-term stability, and excellent tolerance to cross-over effects of methanol in alkaline media for the oxygen reduction reaction(ORR), indicating that these S-doped graphene sheets possess great potential for a substitute for Pt-based catalysts in fuel cells.     

An efficient approach for the total synthesis of balticolid

An efficient stereoselective total synthesis of balticolid has been accomplished starting from known aldehyde. The key steps involved in this synthesis are Sharpless asymmetric epoxidation, Wittig olefination, alkylation of 1,3-dithiane and Yamaguchi macrolactonization.     

Facile synthesis of highly efficient phenyltetraene-based nonlinear optical chromophores for electrooptics

[reaction: see text] A facile synthetic route has been developed to convert an electron-rich, sterically hindered dialkylaminodienone into a conjugated dialkylaminotrienal with good yield. The derived dialkylaminotetraene-type nonlinear optical chromophores possess an all-trans conformation and can be functionalized with fluoro-dendron to provide proper shape modification for poling. Polymers doped with two examples of these chromophores in high concentrations have been poled to afford ultra-large electrooptic coefficients (r(33)) of 208 and 262 pm/V, respectively, at the measuring wavelength of 1.31 mum.     

Highly efficient disulfide bridging polymers for bioconjugates from radical-compatible dithiophenol maleimides

The direct synthesis of dithiophenol maleimide functional polymers by living radical polymerisation is described without the need for protecting group chemistry. The synthesised polymers have been successfully employed as disulfide bridging agents for salmon calcitonin when used in equimolar quantities, negating the requirement for complex purification strategies, traditionally associated with peptide bioconjugation.     

Fast and highly efficient one-pot synthesis of 9-deazaxanthines

SnCl₂ enables a direct, high-yield conversion of 5-nitro-1,3-dialkyl-6-styryl(furyl-, thienyl-vinyl)-uracils to 8-substituted-9-deazaxanthines under very mild experimental conditions. The method has a general applicability and it is compatible with the reactivity of the most common organic functional groups. In slightly experimental different conditions, it allows a high-yield and fast (<5 min) preparation of pure 7-N-hydroxy-9-deazaxanthines.