Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids

Enantiopure 1-acyl-3-hydroxyl-4-CF₂H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF₃-azetidin-2-ones serve as versatile intermediates for the syntheses of CF₂- and CF₃-containing α-hydroxy-β-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF₂H-β-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure 4-formyl-β-lactam that is prepared through [2+2] cycloaddition of acetoxyketene to a 3-methyl-2-butenaldimine, followed by enzymatic optical resolution and ozonolysis. (+)-3-Hydroxy-4-CF₃-β-lactams and (−)-3-hydroxy-4-CF₃-β-lactams can also be readily obtained in enantiopure form through [2+2] cycloaddition of a CF₃-imine with a ketene, followed by enzymatic optical resolution. Practical processes for the preparations of these enantiopure 3-hydroxy-4-R_f-β-lactams as well as their synthetic applications are described.     

Reaction of a 5α-bromo-6β,19-epoxysteroid with BF3·Et2O/Ac2O: An evidence of a cyclic bromonium cation

Treatment of 3β-acetoxy-5-bromo-6β,19-epoxy-5α-androstan-17-one with Ac₂O and BF₃·OEt₂, produced the cleavage of the epoxy moiety and migration of the bromine atom to afford 3β,19-diacetoxy-6α-bromo-5-hydroxy-5β-androst-17-one in high yield.     

Fabrication of MCM-41 mesoporous silica through the self-assembly supermolecule of β-CD and CTAB

Using the self-assembly β-cyclodextrin (β-CD) and cetyltrimethylammonium bromide (CTAB) as structure-directing agents, high-quality ordered MCM-41 silicas have been prepared. Small-angle X-ray diffraction (SXRD), N₂ adsorption-desorption and scanning electron microscope (SEM) techniques were used to characterize the calcined samples. Results showed that the pore structure of the resulting mesoporous silica belonged to the two-dimensional hexagonal structure (space group p6mm). The high-quality hexagonal structure was formed as n?1 (n denotes molar ratio of β-CD to CTAB). N₂ adsorption-desorption curves revealed type IV isotherms, H4 hysteresis loops, for all samples, and H1 hysteresis loops for samples at n=0, 0.1, 1 and 2, respectively. The pore size and the pore wall thickness of the samples increased with the increase in n values, respectively.     

Preparation of both enantiomers of β-(3,4-dihydroxybenzyl)-β-alanine, higher homologues of Dopa

β²-(3,4-Dihydroxybenzyl)-β-alanine [β²-Homo-Dopa, 1] is a novel β-amino acid homologue of Dopa, the most successful therapeutic agent in the treatment of Parkinson's disease. Enantioenriched (R)-1 and (S)-1 were obtained via the diastereoselective alkylation of enantiopure pyrimidinone (R)- and (S)-3, chiral derivatives of β-alanine, with veratryl iodide. The major diastereomeric products (2S,5R)-4 and (2R,5S)-4 were hydrolyzed with 57% HBr, and the desired β-amino acids were purified by silica gel chromatography. Alternatively, enantioenriched (R)- and (S)-1 were prepared by means of the highly diastereoselective alkylation (3,4-dimethoxybenzyl iodide) of open-chain β-aminopropionic acid derivatives (R,R,S)-8 and (S,S,R)-8 containing the chiral auxiliary α-phenylethylamine. Finally, nearly enantiopure (R)- and (S)-1 were obtained by resolution of racemic N-benzyloxycarbonyl-2-(3,4-dibenzyloxybenzyl)-3-aminopropionic acid, rac-12, with (R)- or (S)-α-phenylethylamine, followed by catalytic hydrogenolysis.     

Synthesis of 2-(α-Hydroxyalkyl)-2-Oxazoline under Microwave Irradiation in Bluk

Four 2-(α-hydroxyalkyl)-2-oxazolines and a 2-(α-hydroxy-α,α-diphenyl)-2-benzooxazole were synthesized from β-amimoalcohols and α-hydroxy carboxylic acids under microwave irradiation in the absence of a solvent.     

Separation of oligonucleotides and DNA fragments by capillary electrophoresis in dynamically and permanently coated capillaries,using a copolymer of acrylamide and β-D-glucopyranoside as a new low viscosity matrix with high sieving capacity

New copolymers of acrylamide and β-D -glucopyranoside were synthesized and characterized. The different reactivity of the two monomers towards radical polymerization meant we could control the growth of the polymer chains whose length was inversely related to the number of glucose residues incorporated in the copolymers. The properties of these polymers were investigated in the separation of oligonucleotides and double-stranded DNA by capillary electrophoresis (CE) in coated and uncoated capillaries. The new copolymers were a suitable matrix for CE due to their high-resolving capacity and low viscosity. We also looked into the advantages of a new method of dynamic suppression of electroosmotic flow based on the addition of small amounts (0.03–0.05%) of dimethylacrylamide to the sieving and to the running buffer. A complete test was run on the reproducibility and efficiency of separations carried out in a permanently and dynamically coated capillary, and the advantages and disadvantages of the two methods were compared.     

麝香草的新单萜配糖物的分离与合成

从麝香草(Thymus vulgaris L)的甲醇萃取物中分离出三个单萜配糖物. 用核磁共振光谱确定了它们的结构为对伞花-9-基-β-D-葡糖苷(1), 5-β-D-葡糖苷百里氢醌(2)和2-β-D-葡糖苷百里氢醌(3). 其中1是新化合物, 用以对伞花-9-醇为原料的对映体选择性合成方法确定了化合物1的8位的立体化学为R型.     

A one step synthesis of novel 4-alkoxy-β-lactams by high pressure promoted [2 + 21 cycloadditions of enol ethers and isocyanates derived from amino acids

Abstract

Novel moni-β-lactams derived from esters of amino acids have been prepared in one step by the high pressure promoted [2 + 2] cycloaddition of enol ethers with isocyanates derived from esters of amino acids. The effect of substituents in the enol ether and in the isocyanate on the scope of the synthesis has been demonstrated.     

Biosynthesis and antioxidant activity of 4NRC β-glycoside

This Letter describes glycosylation of 4-Nerolidylcatechol (4-NRC) the major secondary metabolite from Pothomorphe peltata and Pothomorphe umbellata showing remarkable antioxidant, antimalarial, anti-inflammatory, and anti-HIV activities. One step biosynthesis was catalyzed by Cunninghamella echinulata ATCC 9245 and the reaction was undertaken in PDSM medium at 27 °C, 200 rpm for 96 h. After purification by silica gel flash column chromatography the 4-NRC β-glycoside was identified by ultrahigh resolution mass spectrometry and ¹H NMR. The antioxidant activity was evaluated by differential pulse voltammetry.     

Approach for the Direct Synthesis of β-Dichlorosubstituted Acetanilides Using Iodine Trichloride (ICl3) as the Oxidant and Catalyst

A reliable method for direct synthesis of β‐dichlorosubstituted acetanilides is reported. The key transformation involves the oxidative and catalytic cleavage of a carbon‐carbon bond in the presence of iodine trichloride (ICl₃). In this protocol ICl₃ is used not only as the catalyst but also as the oxidant which widely broadens the scope of its application in organic synthetic chemistry.