Synthesis and ring-opening polymerization of α-chloromethyl-α-methyl-β-propiolactone

α-Chloromethyl-α-methyl-β-propiolactone (CMMPL) was synthesized by dehydrohalogenation of α,α-dichloromethyl-β-propionic acid which was obtained by chlorination of α,α-hydroxymethyl-β-propionic acid (DMPA). Due to high strain of the four-numbered ring, CMMPL can be polymerized by ring-opening with or without an initiator. Both electrophiles like trifluoroacetic acid (TFAA) and nucleophiles like triethylamine (TEA) and pyridine, as well as organometallic compounds such as stannous octoate [Sn(Oct)₂)], aluminium triisopropoxide [Al(OⁱPr)₃] and tetrabutyl orthotitanate [Ti(OC₄H₉)₄], were found to be effective initiators. The polymerization can be conducted by either solution or bulk polymerization. P(CMMPL) is insoluble in almost all organic solvents at room temperature. An endothermic peak (ca. 214 ˜ 250°C) attributed to the melting transition of P(CMMPL) was observed in DSC curves. P(CMMPL) tends to have high crystallinity (40% ˜ 60%) as demonstrated by its X-ray diffraction patterns, and the crystallinity was found to vary with the types of initiator used.     

Synthesis of 2,3,4-tri-O-benzyl-[1→6]-α-D-glucopyranan and [1→6]-α-D-glucopyranan with high molecular weight by polymerization of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose

The polymerization mechanism of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D -glucopyranose ( 1 ) was investigated in order to synthesize 2,3,4-tri-O-benzyl-[1→6]-α-D -glucopyranan ( 2a ) and [1→6]-α-D -glucopyranan ( 2b ) (dextran) with high molecular weight. It was found that the optimum polymerization time to obtain high molecular weights was 40min when the monomer was polymerized in methylene chloride at ?60°C. Stereoregular 2a with a \documentclass{article}\pagestyle{empty}\begin{document}$ \overline {DP} _{\rm n} $ of 1800 (M?_n = 777000), which was about twice as high as the highest \documentclass{article}\pagestyle{empty}\begin{document}$ \overline {DP} _{\rm n} $ previously reported, was obtained in 77% yield by polymerizing the monomer with 0.8 mole-% PF₅ as catalyst applying a monomer-to-solvent weight/volume ratio of 50%. 2a with a high molecular weight was debenzylated to give 2b with a \documentclass{article}\pagestyle{empty}\begin{document}$ \overline {DP} _{\rm n} $ of 446 (M?_n = 72300). The α-stereospecificity and the solid state of the synthetic dextran were investigated by means of optical rotation, NMR spectroscopy, and X-ray diffraction pattern.     

Selective ring-opening polymerization of 3,5-anhydro-1,2-O-isopropylidene-α-D-xylofuranose synthesis of [3→5]-D-xylan

The ring-opening polymerization of 3,5-anhydro-1,2-O-isopropylidene-α-D -xylofuranose was studied to investigate the selectivity of ring-opening mode under various polymerization conditions with a number of Lewis acids, anionic and coordinated catalysts. In all the conditions attempted here, the monomer attacks only the C-5 methylene carbon of the active end of the growing chain to form a stereoregular [3→5]-α-D -xylofuranan structure. With removal of the isopropylidene groups of the polymer, a new class of non-hydrolyzable polysaccharides, [3→5]-D -xylan, is obtained.     

31P and 19F NMR spectroscopic studies on ring-opening polymerization of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose by PF5 catalyst

In order to elucidate the catalytic behavior of phosphorus pentafluoride in the polymerization of anhydro sugars, ¹³P and ¹⁹F NMR spectra were measured on a reaction mixture of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D -glucopyranose (LGTBE) and PF₅ with different mole ratios in a temperature range of ?40 to ?80°C. In the ³¹P NMR spectrum measured at low temperatures, there was a total of 16 peaks, which consisted of a broad quintet, a septet, and a sharp quartet, being assigned to the PF₄O-group, to PF, and to POF₃, respectively. These fluoro compounds were also determined by the ¹⁹F NMR spectrum of the reaction mixture. The concentration of PF ions was found to correspond to that of oxonium ions, which are assumed to be actual propagating species, by determining both the concentration of PF from ¹⁹F NMR spectrum and the degree of polymerization of 2,3,4-tri-O-benzyl-α-D -glucopyranan obtained. Formation of the PF₅: LGTBE complex was observed from the ³¹P NMR spectrum of the polymerization system at ?80°C, which exhibits a broad sextet as well as absorptions due to POF₃, PF₄O–, and PF. To confirm the PF₅:LGTBE complex, the NMR measurement of the PF₅: tetrahydropyran complex was carried out. A polymerization mechanism of LGTBE by PF₅ catalyst is discussed on the basis of the NMR measurement of the polymerization system.     

Synthesis of α- and ω-norbornenyl-polybutadiene macromonomers and their ring-opening metathesis polymerization

Norbornene-ended polybutadiene (PBu) macromonomers have been prepared via two different routes: α-norbornenyl-polybutadiene was derived from a norbornene-containing carbanionic initiator, whereas ω-norbornenyl samples were obtained through deactivation of living polybutadienyl anions by a norbornene-based deactivator. Out of four alkylidene complexes tried, the molybdenum alkylidene complex that contains two alkoxide ligands was found to be the most suitable initiator for the ring-opening metathesis polymerization of these macromonomers.     

Synthesis and polymerization of fluorinated acrylic monomers substituted in α-position, 2. Synthesis and polymerization of 2-perfluorohexylethyl α-acetoxyacrylate

The synthesis of 2-perfluorohexylethyl α-acetoxyacrylate (^b) H₂C?C(OAc)CO₂C₂H₄C₆F₁₃ ( 1 ) was performed in two steps starting from pyruvic acid and 2-perfluorohexylethanol (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol) with an overall yield of about 50%. Esterification of pyruvic acid with the adequate fluorinated alcohol was followed by enol acetylation to give monomer 1 . Homopolymerization and copolymerization of 1 are easily carried out. From the kinetic study of the homopolymerization and copolymerization of 1 with styrene, the numerical values of the ratio square of the rate constant of propagation over the rate constant of termination k/k_t and of the copolymerization reactivity ratios r₁ and r₂ of the two monomers were determined.     

Synthesis and polymerization behavior of 2,3-dihydro-1,4-dioxin-2-one and its 3-methyl derivative

The hitherto unknown 2,3-dihydro-1,4-dioxin-2-one ( 7 ) and its 3-methyl derivative 8 have been synthesized for the first time. The olefinic double bond is inserted into the saturated 1,4-dioxanone precursors 3 and 6a/b by a retro-Diels-Alder reaction in the last step of the synthesis. The 1,4-dioxanone systems of 3 and 6 are prepared by reacting a vicinal dialkoxide with α-halogenated acyl halides, thus forming the ester and the ether bond in a one-pot reaction. Monomers 7 and 8 are polymerized by cationic initiation. The resulting products undergo fragmentation to form oligomers in the presence of protic solvents, indicting that ring-opening polymerization of the δ-lactone apparently leads to polyester chain segments.     

Epithelial hyperplasia of usual type expresses both S100-α and S100-β in a heterogeneous pattern but ductal carcinoma in situ can express only S100-α in a monotonous pattern

Immunohistochemical identification of myoepithelial cells using α-smooth muscle actin provides little information about the nature of solid or quasi-solid portions of epithelial hyperplasia and ductal carcinoma in situ (DCIS) because actin-rich myoepithelial cells are usually demonstrated only in the stromal–epithelial junction of both lesions. We studied the differential distribution of α-subunit (S100-α) and β-subunit (S100-β) of S100 protein in actin-negative areas of usual epithelial hyperplasia and DCIS by employing the streptavidin method with monospecific rabbit antibodies against each subunit. All usual epithelial hyperplasias (n=17) were composed of heterogeneous epithelial cell types; cells expressing S100-α and/or S100-β were intermingled with non-expressing cells, resulting in a mosaic-like pattern. On the contrary, DCIS (n=32) uniformly lacked immunoreactive S100-β; S100-α was diffusely expressed in 24 (68.8%) DCIS (three solid/comedo, 13 cribriform, four endocrine, one micropapillary, three papillary variants) and negative in the remaining eight (31.2%) DCIS (one cribriform, two micropapillary, four papillary and one apocrine variants). In conclusion, in contrast to usual epithelial hyperplasia that expresses both S100-α and S100-β in a heterogeneous pattern, DCIS can express only S100-α in a monotonous pattern, possibly signifying unidirectional differentiation toward secretory glandular epithelium.     

Synthesis of polymers containing pseudohalide groups by cationic polymerization, 13. “Living” polymerization of 2-methylpropene initiated by the system 1,4-bis(1-azido-1-methylethyl)benzene/BCl3/dimethyl sulfoxide

Polymerizations of 2-methylpropene (MP) initiated by the system 1,4-bis(1-azido-1-methylethyl)benzene (DAMEB)/BCl₃ in the presence of DMSO were carried out by “all monomer in” (AMI) technique at ?70°C in CH₂Cl₂ solution. FT-IR, ¹H NMR and SEC analyses of polymers (PMP) showed that the M _n versus weight of PMP plot is a straight line without intercept and azide F_n3 and aromatic ring F_? functionalities are close to the theoretical values of 2 and 1, respectively. A polymerization of MP initiated by the system α,ω-diazido-PMP/BCl₃/DMSO led to a final poly(2-methylpropene) (PMP) with an increase of M _n corresponding to the amount of MP introduced and presenting the same functionalities F_N3 and F_? as the starting PMP. These results indicate that the polymerization system MP/DAMEB/BCl₃/DMSO is a “living” one, because in an acceptably large range of molecular weight (M _n < 50000) the Mayo plot 1/DP versus 1/DP ₀ is a straight line. The intercept gives k_trM/k_p = 4 · 10^?5, showing the transfer reaction proceeds at very low rate.     

Synthesis and ring-opening polymerization of 1,4:2,5:3,6-trianhydro-D-mannitol and structure studies by MNDO calculations

Base-catalyzed intramolecular nucleophilic substitution of various dianhydrosorbitol derivatives ( 2, 4 , or 6 ) led to formation of trianhydromannitol ( 7 ), a tricyclic system of three interlinked oxolane rings. By treatment with trifluoromethanesulfonic acid, ring-opening reactions were achieved to give oligomeric soluble material with a number-average degree of polymerization $ \overline {DP} _n \approx 5 - 10 $ Molecular weights were determined by GPC, and by desorptive chemical ionization (DCI) with ammonia a molecular weight assignment gave information on the degree of crosslinking. A complex but consistent picture allows to explain the propagation reactions of protonated trianhydromannitols 8 and 9 , and further reactions of the protonated intermediates 13–15 to result in crosslinked products 16 and 17 . By semiempirical quantum chemical calculations, geometries, energies and charge distributions of 7 as well as its protonated species were obtained. This allowed comparisons with their chemical reactivity and ring-opening specificity.     

Induction and functional characterization of β 2-microglobulin (β2-μ)-free HLA class I heavy chains expressed by β2-μ-deficient human FO-1 melanoma cells

The frequent loss of β2-microglobulin (β₂-μ) in malignant cells has stimulated interest in the functional characteristics of β₂-μ-free HLA class I heavy chains, since this information contributes to assess the impact of β₂-μ abnormalities on the interaction of malignant cells with immune cells. Therefore, the present study has investigated the ability of β₂-μ-free HLA class I heavy chains to modulate NK cell-mediated lysis of melanoma cells and to present melanoma-associated antigen (MAA)-derived peptides to HLA class I-restricted, MAA-specific cytotoxic T lymphocytes (CTL). β₂-μ-free HLA class I heavy chains were induced on B₂m null FO-1 cells by sequential incubation with IFN-α for 48 h at 37 °C and for 24 h at 26 °C. Transfection of cells with a wild-type H-2L^d gene (FO-1L^d) enhanced the induction of β₂-μ-free HLA class I heavy chains under such experimental conditions. β₂-μ-free HLA class I heavy chains expressed on the cell membrane did not protect the B₂m null FO-1 cells from NK cell-mediated lysis. Furthermore, FO-1 cells which express β₂-μ-free HLA-A2 heavy chains following transfection with a wild-type HLA-A2 gene were not lysed by HLA-A2-restricted, MAA-specific CTL lines and clones. These results indicate that association with β₂-μ is required for interaction of HLA class I molecules with NK inhibitory receptors and for peptide presentation to CTL.     

Kinetic determination of stereoselectivity in the anionic polymerization of α-ethyl-α-phenyl-β-propiolactone

The kinetics of the anionic polymerization of optically active α-ethyl-α-phenyl-β-propiolactone (optical purity 16,8%) initiated with bis(triphenylphosphine)iminium acetate was investigated and the rate constants for the homo-(k_ph) and crosspropagation (k_pc) (considering R and S enantiomers as comonomers) were determined. The knowledge of the values of k_ph and k_pc, equal to 1,53·10^?4 and 9,0·10^?51· mol^?1·s^?1, respectively (25°C, CH₂Cl₂ solvent), allowed us to calculate the distribution of homosequences in the polymer prepared from racemic monomer. The concentration of homosequences was slightly higher than calculated for the process with random enchainment of enantiomers. Thus, the content of homodyads, homotriads, and homotetrads equals 63, 40, and 25%, whereas for the random process it was 50, 25, and 13%, respectively. This difference is, however, too small to create homoblocks which could be responsible for the observed crystallinity of these polymers.     

Polymerization of 5,6-anhydro sugar derivatives, 2. Anionic polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose and synthesis of 5,6-glucan

Poly(5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose) ( 1 ) the main chain structure of which is poly(oxyethylene) was obtained by anionic ring-opening polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose ( 2 ) which contains a pendent oxirane ring. Polymerization by strong bases such as sodium hydroxide, potassium hydroxide, cesium hydroxide, and potassium tert-butoxide gave polymers with degrees of polymerization up to sixteen in high yield. The specific rotations of the polymers were almost constant, being mostly in the range from ?44° to ?40°. The factors affecting this polymerization were examined in order to elucidate the best conditions for polymerization. The polymer was hydrolyzed to 5,6-glucan ( 3 ) with trifluoroacetic acid-water at room temperature. The structures of the original polymer 1 and the hydrolyzed one were compared with those prepared by cationic ring-opening polymerization of 2 .     

Studies on the β-form of isotactic polypropylene, 1. Characterization of the β-form and study of the β-α transition during heating by wide angle X-ray diffraction

The conditions for the formation of the β-form of isotactic polypropylene in the presence of a β-nucleator and the β-α transition during heating were studied by wide angle X-ray diffraction. A conditional crystallinity of the β-form, X′_β, and a structural disorder parameter, S, deduced from WAXD data were defined for the characterization of the β-form in addition to the K value. The results show that X′_β and S obviously depend on the content of β-nucleator, and that the β-α transition during heating essentially consists in the melting of the β-form and the successive recrystallization to the α-form.     

Synthesis and radical ring-opening polymerization of 1-phenyl-2-vinylcyclopropane in the presence of TEMPO

Synthesis and radical ring-opening polymerization behavior of 1-phenyl-2-vinylcyclopropane (PhVCP) were examined. PhVCP was synthesized by the coupling reaction of butadiene with phenyldiazomethane, where cis and trans isomers were obtained with the ratio 78 : 22. Radical polymerization of PhVCP was carried out in bulk at 60–180°C with 2,2′-azoisobutyronitrile, benzoyl peroxide, or di-tert-butyl peroxide as initiator to obtain a 1,5-ring-opened polymer with M_n ≈ 1 900. When PhVCP was polymerized in the presence of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), M_n of the obtained polymer increased with time. The radical polymerizability of PhVCP is much lower compared with that of styrene. From the molecular-orbital calculation of both monomers, it has been suggested that this is not caused by an electronic factor of the vinyl group but by side reactions such as the abstraction of a hydrogen atom from the allylic position of PhVCP.     

Polymerization of anhydro sugar derivatives. Cationic polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose and structure of the polymer

The cationic polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose ( 1 ), containing an oxirane ring, gave a polymer whose structure was found to be poly(5,6-anhydro-1,2-O-isopropylidene-α-D -glucofuranose) ( 2 ). Polymerizations with phosphorus pentafluoride, boron trifluoride etherate, stannic chloride, or antimony pentachloride below 10°C for 0,04 to 240h gave yields of 51,7 to 97,5% of polymers with M?_n in the range of 1290 to 9500. Polymerization above 20°C produced insoluble gels. The specific rotations of the polymers changed with the polymerization conditions, being in the range of ?31,6° to ?15,0°. The mechanism of the epoxide polymerization of the 5,6-anhydro sugar derivatives is discussed.     

Amniotic 17-α hydroxyprogesterone and HLA typing for the prenatal diagnosis of 21-α hydroxylase deficiency — congenital adrenal hyperplasia

We have investigated a family with one child affected with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Prenatal determination of 17-α hydroxyprogesterone (17OHP) in amniotic fluid (AF) and HLA typing of amniotic fibroblasts from a pregnancy at risk showed that the fetus was not affected. A healthy cousin with HLA haplotypes identical to those of the proposita (only one being identical by descent) had a normal plasma level of 17OHP. The prenatal diagnosis of a fetus affected with 21-hydroxylase deficiency CAH may be established by the determination of 17OHP in AF. This is a relatively quick procedure that can be confirmed by the HLA genotype, and is mandatory in families with a parent homozygous for an HLA haplotype and in certain recombinant haplotypes in the fetus.