Molecular Basis for the Enantioselective Ring Opening of β‐Lactams Catalyzed by Candida antarctica Lipase B

Lipase B from Candida antarctica (CAL‐B) catalyzes the slow, but highly enantioselective (E>200), ring‐opening alcoholysis of two bicyclic and two 4‐aryl‐substituted β‐lactams. Surprisingly, the rate of the reaction varies with the nature of the alcohols and was fastest with either enantiomer of 2‐octanol. A 0.5‐g scale reaction with 2‐octanol as the nucleophile in diisopropyl ether at 60 °C yielded the unreacted β‐lactam in 39–46% yield (maximum yield is 50%) with ≥96% ee. The product β‐amino acid esters reacted further by polymerization (not isolated or characterized) or by hydrolysis due to small amounts of water in the reaction mixture yielding β‐amino acids (7–11% yield, ≥96% ee). The favored enantiomer of all four β‐lactams had similar 3‐D orientation of substituents, as did most previously reported β‐lactams and β‐lactones in similar ring‐opening reactions. Computer modeling of the ring opening of 4‐phenylazetidin‐2‐one suggests that the reaction proceeds via an unusual substrate‐assisted transition state, where the substrate alcohol bridges between the catalytic histidine and the nitrogen of the β‐lactam. Computer modeling also suggested that the molecular basis for the high enantioselectivity is a severe steric clash between Ile189 in CAL‐B and the phenyl substituent on the slow‐reacting enantiomer of the β‐lactam.     

Epichlorohydrin polymerization using diphenylzinc-cocatalyst systems in benzene solution

Summary Various diphenylzinc-cocatalyst systems were used as initiators of epichlorohydrin polymerization in benzene solution. Water, acetone, butanone, acetophenone and cyclopentanone were employed as cocatalyst but in the most of the cases diphenylzinc alone produced the better conversion to polymer. GPC results suggest the presence of more than one active species for the polymerization initiated by those systems. For diphenylzinc alone as initiator the reaction at 120°C is first order with respect to monomer with k_p=1.21x10 ^-5L mol^-1sec^-1.     

Polymerization of some oxiranes using the diphenylzinc-butanone system in benzene at 60°C

The diphenylzinc-butanone system was used as polymerization catalyst for some oxiranes in benzene solution at 60°C. This system is greatly influenced by the molar ratio of butanone to diphenylzinc, and the maximum catalytic activity for propylene oxide and ethylene oxide was found for a ratio of unity. GPC results strongly suggest the presence of more than one active species for the system. ¹³C NMR analysis indicates that the resulting poly(propylene oxide) has a head-to-tail arrangement. For the polymerization of propylene oxide with butanone/diphenylzinc = 1, after an initial induction period, the reaction was first-order with respect to monomer with k = 2·51 × 10^?5 s^?1. Ethylene oxide polymerizations using butanone/diphenylzinc = 1 and 5 were also first-order with respect to monomer after an initial induction period with k = 7·80 × 10^?6 s^?1 and k = 5·71 × 10^?6 s^?1, respectively. The diphenylzinc-butanone system was not an effective catalyst for styrene oxide polymerization.     

Synthesis of poly(β‐pinene)‐g‐polystyrene from allylic brominated poly(β‐pinene)

Poly(β‐pinene) was brominated by N‐bromosuccinimide on the allylic carbons. Then the brominated product was activated by AlEt₂Cl to initiate the polymerization of styrene to give a β‐pinene/styrene graft copolymer. AlEt₂Cl was selected because it alone could not initiate the polymerization of styrene. The obtained graft copolymer was characterized by GPC, ¹H‐NMR, and DSC measurements, respectively. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 599–603, 2000     

Synthesis,Structure–Activity,and Structure–Stability Relationships of 2‐Substituted‐N‐(4‐oxo‐3‐oxetanyl) N‐Acylethanolamine Acid Amidase (NAAA) Inhibitors

N‐Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator‐activated receptor‐α (PPAR‐α). Compounds that feature an α‐amino‐β‐lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti‐inflammatory effects that are mediated through FAE‐dependent activation of PPAR‐α. We synthesized and tested a series of racemic, diastereomerically pure β‐substituted α‐amino‐β‐lactones, as either carbamate or amide derivatives, investigating the structure–activity and structure–stability relationships (SAR and SSR) following changes in β‐substituent size, relative stereochemistry at the α‐ and β‐positions, and α‐amino functionality. Substituted carbamate derivatives emerged as more active and stable than amide analogues, with the cis configuration being generally preferred for stability. Increased steric bulk at the β‐position negatively affected NAAA inhibitory potency, while improving both chemical and plasma stability.     

Synthesis and characterization of poly[(R,S)‐3‐hydroxybutyrate] telechelics and their use in the synthesis of poly(methyl methacrylate)‐b‐ poly(3‐hydroxybutyrate) block copolymers

Poly[(R,S)‐3‐hydroxybutyrate] oligomers containing dihyroxyl (PHB‐diol), dicarboxylic acid (PHB‐diacid) and hydroxyl‐carboxylic acid (a‐PHB) end functionalities were obtained by the anionic polymerization of β‐butyrolacton (β‐BL). Ring opening anionic polymerization of β‐BL was initiated by a complex of 18‐Crown‐6 with γ‐hydroxybutyric acid sodium salts (for PHB‐diol and a‐PHB) or succinic acid disodium salt (for PHB‐diacid). Dihydroxyl functionalization was formed by the termination of polymerization with bromo‐ethanol or bromo‐decanol while the others were done by protonation. Hydroxyl and/or carboxylic acid functionalized PHB oligomers with ceric salts were used to initiate the polymerization of methylmethacrylate (MMA). PHB‐b‐PMMA block copolymers obtained by this way were purified by fractional precipitation and characterized using ¹H‐NMR and ¹³C‐NMR, gel permeation chromatography (GPC), and thermal analysis (DSC and TGA) techniques. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 965–973, 2002     

Ring‐opening polymerization of ε‐caprolactone by a new yttrium complex: Y[2,2′‐ethylidene‐bis(4,6‐di‐tert‐butylphenoxy)]2(ethylene glycol dimethyl ether)Na(ethylene glycol dimethyl ether)3

The main aims of the work reported here were to synthesize and characterize a new 2,2′‐ethylidene‐bis(4,6‐di‐tert‐butylphenol) (EDBPH₂)‐based bimetal yttrium complex, Y(EDBP)₂(DME)Na(DME)₃ (1c; where DME is ethylene glycol dimethyl ether), which was employed as an efficient initiator for the ring‐opening polymerization of ε‐caprolactone (ε‐CL). From single‐crystal X‐ray diffraction, the solid structure of this new bimetal initiator was well established. Experimental results show that 1c initiates the ring‐opening polymerization of ε‐CL to afford poly(ε‐CL) with a narrow molecular weight distribution (M_w/M_n = 1.09–1.36, 65 °C). Based on an in situ NMR study, a plausible coordination–insertion mechanism is then proposed. The bimetal complex 1c can be used as an initiator for the ring‐opening polymerization of ε‐CL with some living characteristics. A study of the mechanism reveals that DME displacement in 1c by ε‐CL is involved in the initiation process and the propagation may proceed through three pathways by Na? O insertion or Y? O insertion. Copyright © 2009 Society of Chemical Industry     

Concentrated emulsion polymerization for preparation of β‐cyclodextrin‐supported chromatography columns

Concentrated inverse emulsion polymerization was used for making chromatography columns (based on crosslinked polystyrene divinylbenzene (PS‐DVB)) with pore sizes less than 10 μm. According to DSC‐thermal gravimetry thermograms, it was confirmed that the residual monomer concentration after polymerization process is negligible. For application of these columns in chiral chromatography, the β‐cyclodextrin is chemically fixed on the PS‐DVB resin pore surface. The presence of hydroxyl groups in the PS‐DVB resin after chemical modification was confirmed by FTIR spectroscopy. By chemical modification of the PS‐DVB resin, thermal stability increased up to 446°C. The structure of columns was analyzed by scanning electron microscopy (SEM). SEM evaluations showed that the porous structure of PS‐DVB resin was maintained intact after the chemical modification with β‐cyclodextrin. According to X‐ray data, presence of the crystalline domain that is related to β‐cyclodextrin is confirmed.© 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 857–863, 2006     

Effect of β‐cyclodextrin on the solid‐state synthesized polyaniline doped with hydrochloric acid

Polyaniline (PANI) salts doped with hydrochloric acid were prepared by using solid‐state polymerization in the presence of β‐cyclodextrin (β‐CD) at room temperature. The fourier transform infrared (FTIR) spectra, ultraviolet‐visible absorption spectra, X‐ray diffraction patterns were used to characterize the molecular structures of these polymers. Cyclic voltammetry study and conductivity measurements were done to investigate their electrochemical behaviors. The morphology of polymers was studied by the scanning electron microscopy and transmission electron microscopy. The results showed that PANI salts prepared in the presence of β‐CD had different physicochemical characteristics compared with PANI salt prepared in the absence of β‐CD. When the molar ratio of aniline to β‐CD was 80/20, the obtained PANI salt displayed higher crystallinity, conductivity and electrochemical properties. However, these properties were opposite on condition that the molar ratio of aniline to β‐CD was 50/50. The results also revealed that the morphology of PANI salt was affected by β‐CD, especially at aniline/β‐CD molar ratio in the feed of 50/50, in which PANI salt displayed rodlike structure morphology with a diameter of near 80–100 nm. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Ring‐opening copolymerization of L‐lactide with ε‐caprolactone initiated by diphenylzinc

Copolymerization of mixtures of L ‐lactide and ε‐caprolactone has been initiated by diphenylzinc. The reaction conditions were investigated, to discover the effects on yield, molecular weight and microstructure of copolymers obtained. The temperature used varied between 50 and 120 °C, the molar ratio of monomer to initiator ranged between 90 and 1440 mol/mol, and the molar ratio of ε‐caprolactone to L ‐lactide employed was between 100/0 and 0/100 mol/mol. Copolymers were characterized by ¹H‐NMR, ¹³C‐NMR, DSC and gel permeation chromatography. The results indicate that incorporation of L ‐lactide to the growing chain is preferred and ε‐caprolactone is copolymerized after most of the L ‐lactide has been depleted. The microstructure of obtained copolyesters was affected considerably by transesterification reactions. It was observed that increasing reaction temperature, reaction time and concentration initiator was advantageous to the transesterification. The crystallinity of copolyester obtained was determined by differential scanning calorimetry. The results are in good agreement with both molar composition and sequence distribution of copolyesters. Copyright © 2006 Society of Chemical Industry     

Mechanistic study of Sn(Oct)2‐catalyzed ε‐caprolactone polymerization using Sn(Oct)2/BF3 dual catalyst

A novel method was used to investigate the mechanism of Sn(Oct)₂‐catalyzed ε‐caprolactone polymerization by using Sn(Oct)₂/BF₃ dual catalyst. The bulk polymerization was conducted at 110 and 130°C with different Sn(Oct)₂/BF₃ ratios. The polymerization kinetics was followed using gel permeation chromatography, and the molecular structures of the low‐molecular weight polymers were examined using ¹H‐nuclear magnetic resonance (NMR). A polymerization induction period was observed in polymerizations containing the Sn(Oct)₂ catalyst, but it was not observed in the system containing only BF₃. After the induction period, BF₃ and Sn(Oct)₂ initiated the polymerization separately. For Sn(Oct)₂ catalyst with no purposely added alcohol, the actual initiation species is a tin hydroxide species formed in situ by the reaction of Sn(Oct)₂ and adventitious water. For BF₃ catalyst, the active species is the protonic acid formed by the reaction of BF₃ with the adventitious water. When mixed, the Sn(Oct)₂ reacts with the adventitious water faster than the BF₃, preventing the BF₃ catalyzing any polymerizations during the induction period. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Highly active thermally stable β‐nucleating agents for isotactic polypropylene

Calcium salts of suberic (Ca‐Sub) and pimelic (Ca‐Pim) acids were synthesized and implemented as in different grades of isotactic polypropylene (iPP). Propylene homopolymer, as well as random and block copolymers containing these additives, crystallized iPP into pure or nearly pure β modification in the isothermal and nonisothermal crystallization experiments. Recently, Ca‐Sub proved to be the most effective β‐nucleating agent of iPP. The Ca‐Sub nucleating agent widens the upper crystallization temperature range of pure β‐iPP formation up to 140°C. In this study the effect of the these additives on the crystallization, melting characteristics, and structure of the PP were studied. The degree of crystallinity of β‐iPP was markedly higher than that of α‐iPP. A widening in the melting peak of the samples crystallized in a high temperature range was first observed and discussed in regard to literature results of the same phenomenon for α‐iPP. The morphology of the β‐iPP samples was revealed by scanning electron microscopy. Independent of the type of polymer or nucleating agent, hedritic structures were found in the early stages of growth of the β‐spherulites. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2357–2368, 1999     

Synthesis of a vinyl monomer containing β‐cyclodextrin and grafting onto cotton fiber

To chemically bond β‐cyclodextrin (β‐CD), which can form inclusion complexes, acrylamidomethyl CD (CD–NMA) obtained from the acid‐catalyzed reaction of N‐methylolacrylamide (NMA) and β‐CD was grafted onto cellulose fibers using CeIV as the initiator. The double‐bond content of CD–NMA increased with increase in the NMA/CD mol ratio, and a CD–NMA containing a maximum of three molecules of NMA bonded to a CD molecule could be obtained. Since the grafting condition is acidic, the hydrolytic stability of CD–NMA in aqueous nitric acid was studied. The temperature of hydrolysis proved to have a greater effect on the depletion of double bonds from CD–NMA compared with the concentration of the acid. Thus, CD–NMA was grafted onto cellulose fibers at a low temperature, and FTIR analysis of the CD–NMA‐grafted cotton fibers confirmed the chemical bonding of CD–NMA molecules to cellulose. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 438–446, 2001     

Synthesis and characterization of grafting β‐cyclodextrin with chitosan

Two new adsorbents [β‐cyclodextrin–chitosan (β‐CD–CTS) and β‐cyclodextrin‐6–chitosan (β‐CD‐6‐CTS)] were synthesized by the reaction of β‐cyclodextrin (β‐CD) with epoxy‐activated chitosan (CTS) and the sulfonation of the C‐6 hydroxyl group of β‐cyclodextrin with CTS, respectively. Their structures were confirmed by IR spectral analysis and X‐ray diffraction analysis, and their apparent amount of grafting was determined by ultraviolet spectroscopy. The adsorption properties of β‐CD‐CTS and β‐CD‐6‐CTS for p‐dihydroxybenzene were studied. The experimental results showed that the two new adsorbents exerted adsorption on the carefully chosen target. The highest saturated capacity of p‐dihydroxybenzene of β‐CD‐CTS and β‐CD‐6‐CTS were 51.68 and 46.41 mg/g, respectively. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 860–864, 2004     

Preparation and electrorheological characteristics of β‐cyclodextrin–epichlorohydrin–starch polymer suspensions

Three environment friendly β‐cyclodextrin polymer electrorheological (ER) particles (NS‐β‐CDP, WSS‐β‐CDP, and CLS‐β‐CDP) were synthesized by copolymerization through a mixture of β‐cyclodextrin (β‐CD) and epichlorohydrin in the absence of starch or in the presence of water‐soluble and water‐insoluble starch, respectively. The electrorheological properties of suspensions in silicone oil were then investigated under direct current (dc) electric fields. It was found that the yield stress of the typical WSS‐β‐CDP ER fluid was 6.2 kPa in 4 kV/mm, which is 35% higher than that of NS‐β‐CDP and similar to that of CLS‐β‐CDP. In the meantime, it can display a high ER performance even over a range of 65–95°C. The structures of these polymers were characterized by FT‐IR and Raman spectrometry, respectively. The results demonstrated that all of these polymers keep the original structural character of β‐CD and the copolymerizations between starch and β‐CD indeed occur. Furthermore, it was found that there was some relationship between the characteristic strength of polymers and their dielectric properties. Hence, the improvement of copolymer dielectric properties resulted in the enhancement of ER effects. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1681–1686, 2004     

Synthesis of a novel linear water‐soluble β‐cyclodextrin polymer

A novel linear water‐soluble β‐cyclodextrin polymer has been prepared by grafting β‐cyclodextrin on poly[(methyl vinyl ether)‐alt‐(maleic anhydride)]. First, lithium hydride was used to obtain the mono‐alkoxide β‐CD. Grafting of β‐CD derivatives to the polymer backbone was then carried out by an esterification method. Using this method, polymers containing various amounts of β‐CD were synthesized. The resulting grafted polymers were characterized by two complementary methods, ¹H NMR and IR spectroscopy. The first was used to calculate the degree of substitution for the low amounts of β‐CD. The second method was very useful to evaluate the degree of substitution and the molar ratio of CD especially for high amounts of grafting. Our results indicate good agreement between both methods for intermediate rates. Copyright © 2004 Society of Chemical Industry     

RuO4 staining and lamellar structure of α‐ and β‐PP

Monoclinic (α) and hexagonal (β) polypropylene (α‐ and β‐PP) were stained in the vapor of a ruthenium tetroxide solution prepared in situ. The effect of staining on the fusion behavior was investigated using a DSC. A staining duration between 10 and 24 h was found suitable for obtaining a good electron contrast between the crystalline and amorphous regions for TEM examination without causing severe damage to the crystals. The spherulites of the water‐quenched α‐PP were found to be composed of very fine cross‐hatched lamellae whose long period was about 10 nm. In comparison, the β‐PP spherulites crystallized isothermally at 130°C had a category 2 morphology and the lamellae have a long period of 20 nm. The morphology of the spherulite boundary varied depending on the contact angle between the lamellae of the neighboring spherulites. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1529–1538, 1999     

Stereoselective Palladium‐Catalyzed Alkenylation and Alkynylation of Thioglycosides

An efficient and unprecedented palladium‐catalyzed S‐glycosylation reaction of a range of alkenyl and alkynyl halides by using thiosugars as nucleophile partners has been established. With palladium diacetate in combination with Xantphos as the catalytic system, a variety of β‐alkenylthioglycosides as well as β‐alkynylthioglycosides can be prepared in good to excellent yields. The efficiency of this general protocol was well‐demonstrated by the formal synthesis of a leaf‐closure β‐glucosidase inhibitor.

     

Negative effect of stretching on the development of β‐phase in β‐nucleated isotactic polypropylene

On the premise that shear in the slit die of an extruder was minimized as far as possible, β‐nucleated isotactic polypropylene (iPP) was extruded. Simultaneously, once the extrudate (in the melt state) left the die exit, it was stretched at various stretching rates (SRs). For iPP with a low content of β‐nucleating agent (β‐NA), the crystallinity of β‐phase (X_β) initially increases with increasing SR, and then decreases slightly with further increase in SR. However, for iPP containing a higher content of β‐NA, with increasing SR, X_β decreases monotonically, indicating a negative effect of SR on β‐phase formation. Small‐angle X‐ray scattering and polarized optical microscopy experiments reveal that, when SR is less than 30 cm min^?1, the increasing amount of row nuclei induced by increasing SR is mainly responsible for the increase of X_β. In contrast, when SR exceeds 30 cm min^?1, the overgrowth of shish structures unexpectedly restrains the development of β‐phase, and spatial confinement is considered as a better explanation for the suppression of β‐phase. Copyright © 2011 Society of Chemical Industry     

Imprinted β‐cyclodextrin polymers using naringin as template

The objective of this study was to identify a kind of molecular imprinting polymer (MIP) which was suitable for recognizing naringin (NG) in aqueous medium. Based on two crosslinkers (hexamethylene diisocyanate and epichlorohydrin) and two polymerization methods (solution polymerization and emulsion polymerization), four non‐covalent naringin‐β‐cyclodextrine (NG‐β‐CD) imprinted polymers were prepared by using β‐CD as a functional monomer and NG as a template molecule. The binding property and selectivity were evaluated by equilibrium binding experiments. These demonstrated that all the sites in the MIPs show good selective binding ability for NG from naringin dihydrochalcone, a structurally similar molecule. Of the four MIPs, rod‐like 3# MIP which was prepared by emulsion polymerization using hexamethylene diisocyanate as crosslinker exhibited the highest selectivity, its imprinting factor α being 1.53. Scatchard analysis of 3# MIP suggests that there are two classes of binding sites during the MIP's recognition of NG. Additionally, the 3# MIP could be used at least five times without any loss in sorption capacity. Copyright © 2011 Society of Chemical Industry