Synthesis of neoglycolipids for the development of non-viral gene delivery systems

Synthesis of lipid conjugates with galactose as a targeting ligand intended for the development of non-viral systems for the targeted delivery of nucleic acids into hepatocytes is described. 3,4-Diethoxycyclobut-3-ene-1,2-dione (diethyl squarate) was used to bind the galactose moiety to the lipid component.     

Synthesis and molecular tumbling properties of sialyl Lewis X and derived neoglycolipids

The sialyl Lewis X (sLeX) epitope has become a prominent target for biological studies because of its role in inflammation through binding to selectins. This epitope is located at the terminal end in glycosphingolipids and a lactose unit serves as spacer to the ceramide moiety. This paper focuses on the influence of the spacer structure and spacer length in regard to the mobility of the sLeX epitope. To this end sLex neoglycolipids 1a-c, with one, two, or three lactose units as spacer between the sLeX tetrasaccharide epitope and the membrane anchor, were synthesized. The synthetic strategy was also applied to the synthesis of the corresponding Lewis X (LeX) derivatives. The glycolipids were inserted in model membranes, and the tumbling frequencies of the sLex tetrasaccharide epitopes were then analysed by NMR spectroscopy. A nonaethylene glycol spacer decouples the carbohydrate moiety from the membrane mobility while (oligo-)lactoses act as more rigid distance keepers between the Lewis epitope and the surface of the membrane. Quantification of the different degrees of decoupling was possible by analysis of rotational correlation times.     

Synthesis of high-mannose type neoglycolipids: active targeting of liposomes to macrophages in gene therapy

The concise synthesis of five biantennary oligomannose neoglycolipids is presented. Employing a strategy based on the principles of reactivity tuning and orthogonal activation, the oligomannose moieties, isolated from the glycoprotein 63 of the parasite Leishmania mexicana amazonensis, were rapidly assembled taking advantage of common structural motifs found in these N-glycans. Deprotection of all structures was achieved in high yield by hydrogenolysis. The deprotected glycoconjugates were subsequently coupled to a cholesteroldiamine derivative using diethylsquarate as a linker. The resulting neoglycolipids will be used as additives to cationic liposome formulations in the active targeting of liposomes to macrophages.     

Synthesis of mannose-containing neoglycolipids as a component of targeted delivery system for transfer of nucleic acids into antigen-presenting cells

Two approaches to the preparation of mannose-containing neoglycolipid, designed for development of nonviral targeted delivery system for transfer of nucleic acids into antigen-presenting cells, were described. They differed from each other in the binding of the targeting ligand and the lipid anchor, which was effected either through the formation of an amide bond or via the chemoselective binding agent 3,4-diethoxycyclobut-3-ene-1,2-dione.     

Chemical and enzymatic synthesis of neoglycolipids in the presence of cyclodextrins

The efficiency of cyclodextrins (CDs), α-CD, β-CD and γ-CD, for the blotting of hydrophobic substrates to water-soluble polymers and for the synthesis of neoglycolipids using glycosyltransferase is described. CDs did not disturb HPLC purification and did not bring lather. These merits are superior to surfactants commonly used in such a case. The utility of CDs as a novel and efficient supporting material for enzymatic glycosylation is also discussed.     

Design, synthesis, and properties of neoglycolipids based on ethylene glycoles conjugated with lactose as components of targeted delivery systems of biologically active compounds

Synthesis has been developed of a series of new aliphatic lactose derivatives as components of liposomal targeted delivery systems distinguished by the length and the number of aliphatic chains and also by the length of the spacer fragment. The structure of compounds synthesized has been established by means of 1H NMR spectroscopy.     

Multicomponent synthesis of Ugi-type ceramide analogues and neoglycolipids from lipidic isocyanides

Unique types of ceramide and glycolipid architectures were obtained by means of Ugi reactions incorporating lipidic isocyanides as surrogates of sphingolipids. The multicomponent nature of this approach allowed for a highly efficient assembly process, wherein two of the components provided the lipidic tails while a third one incorporated either the functionality suitable for the conjugation to sugar or the sugar moiety itself. Two dissimilar strategies were implemented: (i) the initial assembly of ceramide analogues followed by glycosylation to produce a glycolipid skeleton and (ii) the one-pot construction of glycolipid frameworks by condensation of lipidic isocyanides either with lipidic amines and oligosaccharidic acids or with fatty acids and oligosaccharidic amines. Whereas both approaches are amenable for accessing analogues of anticancer glycolipids, the latter one proved to have greater potential owing to its more straightforward and efficient character. Overall, the methodology developed shows great promise toward the massive (eventually combinatorial) production of neoglycolipids suitable for biological screening.     

An efficient synthesis of novel carbocyclic nucleosides with use of ring-closing metathesis from D-lactose

This paper describes an efficient synthetic route for various types of novel carbocyclic nucleosides. The required stereochemistry of the targeted nucleosides was successfully obtained with use of Grubbs cyclization and Trost allylic alkylation from the carbohydrate chiral template "D-lactose".     

Synthesis of aurones based on usninic acid

(+)-Usninic acid was brominated at the acetyl group located on the aromatic ring. Aurones were synthesized based on the intramolecular cyclization of monobrominated (+)-usninic acid.     

Synthesis of semiaromatic polyamides based on decanediamine

<正>Long chain semiaromatic polyamides were synthesized by the reactions of decanediamine with various aromatic diacids and characterized by Fourier transform infrared spectroscopy(FT-IR) and nuclear magnetic resonance(~1H-NMR). The thermal behaviors were determined by differential scanning calorimetry(DSC) and thermogravimetric analysis(TGA). The solubility,dynamic mechanical,physical and mechanical properties of the polyamides have also been investigated.The resultant polyamides have intrinsic viscosity ranging from 1.7 dL/g to 2.1 dL/g.Their melting temperatures range from 305℃to 343℃,and the glass transition temperatures fall in the range of 125-130℃.The tensile strength of the polyamides is above 100 MPa.     

Synthesis of block copolymers based on polycaprolactam-polybutadiene

Polyamide-polybutadiene segmented block copolymers of well defined structure and composition have been synthesized using α,ω-di-carboxyl-terminated polybutadiene (CTPB) as the initiator for the polymerization of caprolactam (CL) in bulk at 240°C. Both the yield and viscosity increased with the polymerization time and with the CL content in the feed. The segmented copolymers were characterized by i.r. spectra and elemental analysis. The thermal stability of CTPB was also examined using various types of antioxidants in various amounts.     

Synthesis of cyclic phosphites based on D-mannitol

Conclusions Cyclic phosphites based on D-mannitol were synthesized by transesterification of trialkylphosphites with D-mannitol, as well as by its interaction with alkyldichlorophosphites in the presence of a base.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1626–1627, July, 1969.     

Synthesis of hydrogels based on silicon polyolates

Biologically active hydrogels based on silicon polyolates, which are the products of reactions of tetraethoxy- and methyltriethoxysilanes with polyols (1,2-propanediol, glycerol, polyethylene glycol), were synthesized. The optimal conditions for hydrogel formation and hydrogel composition were determined. The acute toxicity and transcutaneous and wound-healing activities of the synthesized compounds were studied. The experimental results show that hydrogels based on silicon polyolates can be recommended for further preclinical and clinical tests with the purpose of their use in medical practice both as self-sufficient agents and ointment bases of pharmaceutical compositions with wound-healing, regenerative, and transcutaneous action.     

Synthesis of 1,3-oxazine derivatives based on diketene

Reaction of diketene with potassium cyanate in acetic acid gives 6-methyl-2,3-dihydro-2,4-diketo-1,3-oxazine, also formed by cyclizing acetoacetylurethane, or by treating ammonium thiocyanate with diketene in the presence of mercuric acetate. Acetylation of N-trisubstituted ureas with ketene in acetic acid gives N-alkyl derivatives of 6-methyl-2,3-dihydro-2,4-diketo-1,3-oxazine.     

Synthesis of azomethines based on 4-formylphenyl m-carboranyl-C-methanoate

A preparative method for the synthesis of m-carborane azomethines via the condensation of mcarborane-C-4-formylphenyl methanoate with aliphatic, cycloaliphatic, and aromatic amines was developed.     

Synthesis and characterization of copolymers based on benzothiadizole-thiophene-phenylenevinylene

<正>Two novel copolymers based on benzothiadizole-thiophene-phenylenevinylene have been synthesized through palladium catalyzed triple-bond polycondensation method.The copolymers exhibit good solubility in common organic solvents such as CHCl_3,CH_2Cl_2 and THF.The structures and properties of the two copolymers are characterized by FT-IR, ~1H-NMR,UV-Vis absorbance(Abs),gel permeation chromatography(GPC),thermal gravimetric analysis and cyclic voltammetry(CV).The copolymers of P_1 and P_2 show absorption spectra with maximum peak at 532 nm and 573 nm in solution,respectively.Compare to their monomers M_1 and M_2,the absorption peaks of P_1 and P_2 were red-shifted by 34 nm and 54 nm respectively.Thermal gravimetric analysis demonstrated that the polymers were stable and little weight loss was observed below 300℃.Cyclic voltammetry experiments showed that the band gaps of the copolymers were 1.81 eV and 1.62 eV,respectively,suggesting their potential for applications as organic solar cell materials.     

Synthesis of 1,3,4-oxazaphospholines based on phosphorylated carbamates

Addition of alcohols to bis(chloromethyl)phosphinoyl isocyanate, as well as the reaction of bis(chloromethyl)phosphinoyl chloride with urethanes or their silylated derivatives, gave the corresponding phosphorylated carbamates which undergo cyclization into 1,3,4-oxazaphospholines under the action of Et₃N. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 810–811, April, 1999.