Substrate Range of the Titanium TADDOLate Catalyzed Asymmetric Fluorination of Activated Carbonyl Compounds

The substrate range of the [TiCl₂(TADDOLate)] (TADDOL=α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol)‐catalyzed asymmetric α‐fluorination of activated β‐carbonyl compounds has been investigated. Optimal conditions for catalysis are characterized by using 5 mol‐% of TiCl₂(naphthalen‐1‐yl)‐TADDOLate) as catalyst in a saturated (0.14 mol/l) MeCN solution of F‐TEDA (1‐(chloromethyl)‐4‐fluoro‐1,4‐diazoniabicyclo[2.2.2]octane bis‐[tetrafluoroborate]) at room temperature. A series of α‐methylated β‐keto esters (3‐oxobutanoates, 3‐oxopentanoates) with bulky benzyl ester groups (60–90% ee) or phenyl ester (67–88% ee) have been fluorinated readily, whereas α‐acyl lactones were also readily fluorinated, but gave lower inductions (13–46% ee). Double stereochemical differentiation in β‐keto esters with chiral ester groups raised the stereoselectivity to a diastereomeric ratio (dr) of up to 96.5 : 3.5. For the first time, β‐keto S‐thioesters were asymmetrically fluorinated (62–91.5% ee) and chlorinated (83% ee). Lower inductions were observed in fluorinations of 1,3‐diketones (up to 40% ee) and β‐keto amides (up to 59% ee). General strategies for preparing activated β‐carbonyl compounds as important model substrates for asymmetric catalytic α‐functionalizations are presented (>60 examples).     

Synthesis of Aryl α,α-Difluoroalkyl Ketones as Potent Inhibitors of Cholesterol Esterase

Aryl α,α-difluoroalkyl ketones were synthesized from the reaction of ethyl α,α-difluoroacylate with aryl lithium at ?78°C or from the coupling of aryl iododifluoromethyl ketone with 1-alkene in the presence of tetcrakis(triphenylphosphine)palladium(0). These compounds were potent inhibitors of pancreatic cholesterol esterase with K_i values in the range 15 μM-20 nM.     

Mn(III)‐Mediated Chlorination of Conjugated Ketones

Mn(III)‐Cl formed by the reaction of Mn(OAc)₃ and hydrochloric acid in situ, reacted with α,β‐unsaturated ketones readily to afford α,β‐dichloroketones in good yields under mild conditions. The products are key precursors for synthesis of conjugated alkynones and other organic compounds.     

On the exotherm of polyacrylonitrile. II. Examination of deuterated polymers

A series of α-, β,β-, and α,β,β-deuterium-labelled acrylonitrile monomers were prepared and polymerized. Secondary deuterium isotope effects on the polymerization and on the pyrolysis reactions that precede carbon fiber formation were observed. When deuterium is in the α-position, the polymerization rate is greater and the molecular weight is higher. It is proposed that either the propagation rate constant or both that constant and the termination rate constant are increased on deuterium substitution. In differential scanning calorimetry, the polyacrylonitrile exotherm occurs at higher temperatures and is narrower when deuterium is substituted at the α-position. On the other hand, the thermal gravimetric analysis activation energy for weight loss of polymer at temperatures below the acrylic exotherm is lower when deuterium is in the α-position, relative to the α-hydrogen polymers. As there is no correlation between the weight loss energy of activation and the various exotherm parameters, the weight loss energy of activation and the various exotherm parameters, the weight loss and exotherm are considered to be independent events. Examination of the distribution of deuterium substituted ammonia species evolved during 100–240°C thermal treatment of the α-and β, β-deuterated polyacrylonitriles provides a clear indication that both the α- and β-positions are directly involved in hydrogen migration to nitrogen, but the mechanism of ammonia generation remains unclear. © 1995 John Wiley & Sons, Inc.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

Macrocycles IV. Macrocyclic polylactones as bifunctional monomers for polycondensations

Tin containing macrocyclic polylactones were prepared by di-n-butyl-2-stanna-1,3-dioxepane-initiated polymerizations of ε-caprolactone in bulk. The average ring size was varied from 10 to 100 monomer units via the monomer/initiator (M/I) ratio. Addition of terephthaloyl or sebacoyl chloride to the in situ prepared macrocycles yielded polycondensates under elimination of di-n-butyl tin dichloride. The molecular weights increased with the reaction temperature (e.g., 80–140°C) and with the size of the macrocycles. Number-average molecular weights (M_ns) up to 90,000 and polydispersities between 1.65 and 2.0 were obtained. Further polycondensations were conducted with isophthaloyl chloride, 4,4′-biphenyldicarbonylchloride and 4,4′-phenylenebisacryloylchloride. Several polycondensations were performed with macrocyclic poly (δ-valerolactone) and poly (β-D ,L -butyrolactone). In those cases the increase of the molecular weight was lower. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1373–1378, 1998     

Heat-resistant resins obtained from polymer precursors bearing β,β′-dicyanovinyl terminal groups

Certain polymer precursors of the general formula: where A is an aromatic structure bearing ester, amide, azomethine, or imide linkages were synthesized. Particularly, 4-hydroxybenzaldehyde was condensed with malonitrile to afford 4-hydroxy-β,β′-dicyanostyrene which reacted with a half molar amount of terephthaloyl dichloride in the presence of an acid acceptor. In addition, 3-nitrobenzaldehyde was condensed with malonitrile to yield 3-nitro-β,β′-dicyanostyrene that was catalytically hydrogenated to the corresponding amine. The latter reacted with a half molar amount of terephthaloyl dichloride, terephthaldehyde, pyromellitic dianhydride, or benzophenone tetracarboxylic dianhydride. The polymer precursors were characterized by elemental analyses as well as IR and ¹H-NMR spectroscopy. Their curing behavior was investigated by DTA. Crosslinked polymers were obtained by curing the monomers at 300°C for 24 h. They were stable up to 407–437°C in N₂ and afforded an anaerobic char yield of 65–50% at 800°C. The thermal stability of resins was correlated with their chemical structures. © 1993 John Wiley & Sons, Inc.     

Slightly Cross‐Linked Polyrotaxanes Made by Linking α‐Cyclodextrins Entrapped in Polyrotaxanes Using Hexamethylene Diisocyanate

In this study polyrotaxane (PR)‐based triblock copolymers were first synthesized via the atom transfer radical polymerization (ATRP) of N‐isopropylacrylamide initiated with the self‐assembly of a distal 2‐bromoisobutyryl end‐capped Pluronic 17R4 with a varying amount of α‐cyclodextrins (α‐CDs) in the presence of CuCl/PMDETA at 25°C in aqueous solution. The α‐CDs entrapped on the copolymer chain were then linked with hexamethylene diisocyanate to give rise to novel slightly cross‐linked polyrotaxanes (SCPRs) in DMF at 45°C. The structures of the PR‐based triblock copolymers and SCPRs were characterized by ¹H NMR, ¹³C CP/MAS, GPC and TGA analyses. The number‐average molecular weight of the resulting SCPRs was nearly three and five times of their precursor after linking with a low polydispersity index range of 1.08–1.28. The thermo‐responsive transition of both PR‐based supramolecular polymers in aqueous solution was demonstrated by turbidity measurements and the self‐aggregated morphologies were also evidenced by TEM observations.     

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

A series of pentapeptide derivatives containing α,α‐disubstituted α‐amino acids have been prepared by a combination of the ‘azirine/oxazolone method’ and segment condensations. X‐Ray crystal‐structure determinations of the molecular structures confirmed the presence of helical conformations stabilized by β‐turns of type III or III′. Pentapeptides containing (R)‐Phe(2Me) form a right‐handed helix, whereas those containing (S)‐Phe(2Me) adopt a left‐handed helical structure.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Efficient zinc initiators supported by NNO‐tridentate ketiminate ligands for cyclic esters polymerization

A series of zinc benzylalkoxide complexes, [LⁿZn(μ‐OBn)]₂ (L = L ¹ H – L ⁵ H ), supported by NNO‐tridentate ketiminate ligands with various electron withdrawing‐donating subsituents have been synthesized and characterized. X‐ray crystal structural studies revealed that complexes 2b and 4b are dinuclear bridging through the benzylalkoxy oxygen atoms with penta‐coordinated metal centers. All the metal complexes have acted as efficient initiators for the ring‐opening polymerization of L ‐lactide (within 12 min, 0 °C). Remarkably, a molecular weight of PLLA up to 580,000 can be achieved using [(L⁵Zn(μ‐OBn)]₂ ( 5b ) as an initiator. The kinetic studies for the polymerization of L ‐lactide with complex 3b at ?10 °C corresponded to first‐order reactions in the monomer. The ring‐opening polymerization (ROP) of ε‐caprolactone, ε‐decalactone, β‐butyrolactone and their copolymer with complex 3b was investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Characterization of an Isozyme of β-Glucosidase from Sweet Almond

A sweet almond β-glucosidase (EC 3.2.1.21) isozyme was purified from commercial crude product. The process of purification consisted of a Protein-Pak Q anion exchange chromatography following by a Superdex 75 HR gel filtration separation. The purified enzyme is a monomeric glycoprotein with molecular weight of 58 kDa and pI=4.55 which is distinguished from reported isozymes. The enzyme has apH optimum in the range of 5.2-5.6 when p-nitrophenyl-β-D-glycopyranosides are used as substrate and is stable up to 50 °C at that pH range. The purified protein also exhibits profound β-galactosidase and σ-L-arabinosidase activity. The study of substrate specificity revealed that lacking of hydroxymethyl group at C-5 of glycosides resulted in higher affinity for substrate binding to enzyme, whereas the chemical step of hydrolysis (k_cst) was prevented significantly. The pH activity profile displayed a bell-shaped curve for all measured p-nitrophenyl-β-D-glycopyranosides with apparent pK₁ and pK₂ values of 4.4-4.7 and 6.2-6.4, respectively. This isozyme was strongly inhibited by δ-gluconolactone (K_i = 160 μM) and 4-phenylimidazole (K_i = 17.8 μM) reversibly at pH 6.2. Among the tested glycoses, the binding affinity of N-acetyl-β-D-glucosamine to the enzyme (K_l = 52 mM) was 6 times stronger than that of glucose and its epimers.     

Novel and Efficient One Pot Condensation Reactions between Ketones and Aromatic Alcohols in the Presence of CrO3 Producing α,β‐Unsaturated Carbonyl Compounds

We report a new, effective and simple method for preparing α,β‐unsaturated carbonyl compounds by reacting ketones and aromatic alcohols at 56°C in the presence of CrO₃ (CrO₃ acts as an oxidant and also a catalyst) for around 10 h. The condensation reactions occurred effectively among a wide combination of ketones and alcohols. The procedure is simple and the yields can be high up to 98%. And a probable mechanism is proposed.     

Conformational structure of peptides containing dehydroalanine: Formation of β‐bend ribbon structure

α,β‐Unsaturated amino acids (dehydroamino acids) have been found in naturally occurring antibiotics of microbial origin and in some proteins. Due to the presence of the C_αC_β double bond, the dehydroamino acids influence the main‐chain and the side‐chain conformations. The lowest‐energy conformational state of the model tripeptides, Ac–X–ΔAla–NHMe, (X=Ala, Val, Leu, Abu, or Phe) corresponds to ϕ₁=−30°, ψ₁=120° and ϕ₂=ψ₂=30°. This structure is stabilized by the hydrogen bond between CO of the acetyl group and the NH of the amide group, resulting in the formation of a 10‐membered ring. In the model heptapeptide containing ΔAla at alternate position with Ala, Abu, and Leu, the lowest‐energy conformation corresponds to ϕ=−30° and ψ=120° for all the Ala, Abu, and Leu residues and ϕ=ψ=30° for all ΔAla residues. A graphical view of the molecule in this conformation reveals the formation of three hydrogen bonds involving the CO moiety of the ith residue and the NH moiety of the i+3th residue, resulting in a 10‐membered ring formation. In this structure, only alternate peptide bonds are involved in the intramolecular hydrogen‐bond formation unlike the helices and it has been named the β‐bend ribbon structure. The helical structures were predicted to be the most stable structures in the heptapeptide Ac–(Aib–ΔAla)₃–NHMe with ϕ=±30°, ψ=±60° for Aib residues and ϕ=ψ=±30° for ΔAla residues. The computational results reveal that the ΔAla residue does not induce an inverse γ‐turn in the preceding residue. It is the competitive interaction of small solvent molecules with the hydrogen‐bonding sites of the peptide which gives rise to the formation of an inverse γ‐turn (ϕ₁=−54°, ψ₁=82°; ϕ₂=44°, ψ₂=3°) in the preceding residue to ΔAla. The computational studies for the positional preference of ΔAla in the peptide containing one ΔAla and nine Ala residues reveals the formation of a 3₁₀ helical structure in all the cases with the terminal preferences for ΔAla, consistent with the position of ΔAla in the natural antibiotics. The extended structures is found to be the most stable for poly‐ΔAla. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 72: 15–23, 1999     

Chromatographic separation of benzo(a)pyrene isomers on nematic liquid crystal GC and polymeric reversed-phase HPLC phases

Summary The use of two nematic liquid crystals (BABT and BPhBT) as GC stationary phases for the separation of monohydroxybenzo(a)pyrenes. as their TMS ethers, and monomethylbenzo(a)pyrenes was developed and compared with the separation of these isomers by HPLC using a polymeric ODS reversed-phase column. It was found that while HPLC and GC gave comparable separation of the hydroxy isomers, 10 out of 12 separated, better separation of the methyl isomers was obtained using HPLC. A simultaneous use of both HPLC and GC would resolve the twelve hydroxy isomers in about 70min. The results indicated that HPLC, using polymeric reversed-phase columns, is as powerful a tool as GC using nematic liquid crystal phases, for the separation of benzo(a)pyrene isomers. A discussion of the effect of solute length-to-breadth ratio on elution order is presented.Presented in part at the 1981 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, Atlantic City, NJ; paper No. 51.     

Structure and Isotope Effects of the β‐H Agostic (α‐Diimine)Nickel Cation as a Polymerization Intermediate

Single‐crystal X‐ray characterization of cationic (α‐diimine)Ni‐ethyl and isopropyl β‐agostic complexes, which are key intermediates in olefin polymerization and oligomerization, are presented. The sharp Ni‐C_α‐C_β angles (75.0(3)° and 74.57(18)°) and short C_α−C_β distances (1.468(7) and 1.487(5) Å) provide unambiguous evidence for a β‐agostic interaction. An inverse equilibrium isotope effect (EIE) for ligand coordination upon cleavage of the agostic bond highlights the weaker bond strength of Ni−H relative to the C−H bond. An Eyring plot for β‐hydride elimination–olefin rotation–reinsertion is constructed from variable‐temperature NMR spectra with ¹³C‐labeled agostic complexes. The enthalpy of activation (ΔH ^≠) for β‐H elimination is 13.2 kcal mol⁻¹. These results offer important mechanistic insight into two critical steps in polymerization: ligand association upon cleavage of the β‐agostic bonds and chain‐migration via β‐H elimination.     

Capillary electrophoretic separation and computational modeling of inclusion complexes of β‐cyclodextrin and 18‐crown‐6 ether with primaquine and quinocide

The antimalarial drug primaquine (PQ) and its contaminant, the positional isomer quinocide (QC) have been successfully separated using capillary electrophoresis with either β‐cyclodextrin (β‐CD) or 18‐crown‐6 ether (18C6) as chiral mobile phase additive. The interactions of the drugs with cyclodextrins and 18C6 were studied by the semiempirical method (Parametric Model 3) PM3. Theoretical calculations for the inclusion complexes of PQ and QC with α‐CD, β‐CD and 18C6 were performed. Data from the theoretical calculations are correlated and discussed with respect to the electrophoretic migration behavior. More stable complexes are predicted for the PQ–β‐CD and PQ–18C6 complexes. The coelution of PQ and QC when α‐CD was used as buffer additive can be explained by their comparable stabilities of the inclusion complex formed, while significant differences in the complexation stabilities of the drugs with β‐CD is responsible for their separation. The stronger hydrogen bonding in PQ–18C6 system is responsible for the separation between PQ and QC when 18C6 was used as chiral mobile phase additive. Copyright © 2009 John Wiley & Sons, Ltd.     

Insights into the Synthesis of Steroidal A‐Ring Olefins

The classical synthesis, followed by purification of the steroidal A‐ring Δ¹‐olefin, 5α‐androst‐1‐en‐17‐one ( 5 ), from the Δ¹‐3‐keto enone, (5α,17β)‐3‐oxo‐5‐androst‐1‐en‐17‐yl acetate ( 1 ), through a strategy involving the reaction of Δ¹‐3‐hydroxy allylic alcohol, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ), with SOCl₂, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ²‐olefin 6 as a by‐product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5 . The same synthetic strategy was applied, using the Δ⁴‐3‐keto enone, 3‐oxoandrost‐4‐en‐17β‐yl acetate ( 8 ), as starting material, to prepare the potent aromatase inhibitor Δ⁴‐olefin, androst‐4‐en‐17‐one ( 15 ). Unexpectedly, a different aromatase inhibitor, the Δ^3,5‐diene, androst‐3,5‐dien‐17‐one ( 12 ), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8 . The data now presented show the unequal reactivity of the two steroidal A‐ring Δ¹‐ and Δ⁴‐3‐hydroxy allylic alcohol intermediates, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ) and 3β‐hydroxyandrost‐4‐en‐17β‐yl acetate ( 9 ), towards SOCl₂, and provides a new strategy for the preparation of the aromatase inhibitor 12 . Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by‐products.     

High‐performance liquid chromatographic enantioseparation of fluorinated cyclic β3‐amino acid derivatives on polysaccharide‐based chiral stationary phases. Comparison with nonfluorinated counterparts

The stereoisomers of five fluorinated cyclic β³‐amino acid derivatives and their nonfluorinated counterparts were separated on chiral stationary phases containing as chiral selectors cellulose tris‐(3,5‐dimethylphenyl carbamate), cellulose tris‐(3‐chloro‐4‐methylphenyl carbamate), cellulose tris‐(4‐methylbenzoate), cellulose tris‐(4‐chloro‐3‐methylphenyl carbamate), amylose tris‐(3,5‐dimethylphenyl carbamate) or amylose tris‐(5‐chloro‐2‐methylphenyl carbamate). The enantioseparations were carried out in normal‐phase mode with n‐hexane/alcohol/alkylamine mobile phases in the temperature range 5–40 °C. The effects of the mobile phase composition, the nature and concentration of the alcohol and alkylamine additives, the structures of the analytes and temperature on the separations were investigated. Thermodynamic parameters were calculated from plots of ln α vs. 1/T. The Δ(ΔH°) values ranged between ?5.0 and +1.6 kJ/mol, while Δ(ΔS°) varied between ?12.6 and +5.7 J/mol/K. The enantioseparation was enthalpically controlled, the retention factor and the separation factor decreasing with increasing temperature, but entropically controlled separation was also observed. The elution sequence was determined for all of the investigated analytes. Copyright © 2016 John Wiley & Sons, Ltd.     

Thermally reversible covalently bonded linear polymers prepared from a dihalide monomer and a salt of dicyclopentadiene dicarboxylic acid

Alkali and earth‐alkali salts of dicyclopentadiene dicarboxylic acid (DCPDCA) were prepared and employed as monomers in the polyesterification with an α,ω‐dihalide monomer, such as 1,4‐dichlorobutane (DCB), 1,4‐dibromobutane (DBB), α,α′‐dichloro‐p‐xylene (DCX), and α,α′‐dibromo‐p‐xylene (DBX). Novel linear polymers that possessed repeating moieties of dicyclopentadiene ( DCPD ) in the backbone were thus prepared. The IR and NMR spectra indicated that poly(tetramethylene dicyclopentadiene dicarboxylate) (PTMDD) with a number‐average molecular weight (M_n ) of about 1× 10⁴ and poly(p‐xylene dicyclopentadiene dicarboxylate) (PXDD) with a M_n of 4–6 × 10³ were obtained with an yield of about 80% via the polyesterification of the alkali salts with DBB and DCX, respectively. The reaction was carried out in the presence of a phase transfer catalyst, such as BzMe₃NBr or poly(ethylene glycol), in DMF at 100 °C for 4 h. Oligomers with a lower M_n (1–2 × 10³) were obtained when the earth‐alkali salts were employed as salt monomers. Compared to the irreversible linear polymers, poly(p‐xylene terephthalate) (PXTP) and poly(p‐xylene maleate) (PXM), prepared through the reaction between DCX and the potassium salts of terephthalic and maleic acid, respectively, the specific viscosities (η_sp) of the new linear polymers increased abnormally with the decrease of the temperature from 200 °C to 100 °C. This occurred due to the thermally reversible dedimerization/redimerization of  DCPD moieties of the backbone of the polymers via the catalyst‐free Diels–Alder/retro Diels–Alder cycloadditive reactions. The ratio of the η_sp at 100 °C and 200 °C of the reversible polymers was found to be much higher than that of PXTP and PXM, even when the heating/cooling cycle was carried out several times under a N₂ atmosphere. The obtained results indicated that thermally reversible covalently bonded linear polymer can be obtained by introducing the  DCPD structure into the backbone of the polymer through the polymerization of a monomer containing the  DCPD moiety. The reversible natures of the polymers and oligomers might be useful in preparing easily processable and recyclable polymers and thermosensor materials. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1662–1672, 2000