Decarboxylative allylation using sulfones as surrogates of alkanes

Alpha-sulfonyl functional groups are traceless activating groups that facilitate catalytic decarboxylative allylations in high yield yet can be cleaved to allow the synthesis of simple allylated alkanes. Substrate studies suggest that decarboxylation to form an alpha-sulfonyl anion is rate-limiting. Furthermore, the anion is formed regiospecifically under formally neutral conditions.     

Preparation of New Multiarmed RAFT Agents for the Mediation of Vinyl Acetate Polymerization

Summary: In this study five xanthate (Reversible Addition-Fragmentation chain Transfer (RAFT)/Macromolecular Design through Interchange of Xanthates (MADIX)) agents were synthesized, namely monofunctional, difunctional, trifunctional and tetrafunctional species of the form SC(O-Z)-S-R, with different leaving groups and different activating moieties some of which are completely novel. Polyvinyl acetates (PVAc) in the form of linear, three armed and four armed star shaped polymers were then successfully synthesized in reactions mediated by these xanthate RAFT/MADIX agents.     

Characterization of the cereulide NRPS alpha-hydroxy acid specifying modules: activation of alpha-keto acids and chiral reduction on the assembly line

Several nonribosomal peptide natural products are composites of alpha-hydroxy acid and alpha-amino acid monomers. Cereulide, the emetic toxin from the human pathogen Bacillus cereus, and valinomycin, from Streptomyces spp., are closely related macrocyclic K+ ionophores. The macrocyclic core of each natural product contains alternating peptide (six) and ester (six) bonds, and their cyclododecadepsipeptide structures consist of a tetradepsipeptide unit repeated three times. Here we overexpress the cereulide NRPS alpha-hydroxy acid specifying modules from CesA and CesB and demonstrate that each contains an alpha-keto acid activating adenylation domain and a chiral alpha-ketoacyl-S-carrier protein reductase (alpha-KR). The logic used by the cereulide NRPS is likely at work in the valinomycin NRPS and may be the general strategy used in bacterial NRPSs to form alpha-hydroxy acid containing natural products.     

PTFE超细颗粒的表面活化与化学接枝

采用钠萘络合物化学腐蚀液对聚四氟乙烯(PTFE)超细颗粒表面进行活化, 对活化后的表面用氨基十一酸碳链进行化学接枝, 并用IR和XPS技术对活化及接枝前后颗粒的表面结构和价键状态进行了表征. 结果表明：活化后的PTFE超细颗粒表面上存在羟基、羰基、羧基等活性官能团, 并出现炭化现象；氨基十一酸的氨基能与表面羟基发生缩合反应, 并接枝于PTFE超细颗粒表面.     

Surface-grafting of phosphates onto a polymer for potential biomimetic functionalization of biomaterials

In the human body, phosphate groups play important roles in signaling and the biological functions of proteins and peptides. Despite the importance of phosphate groups, polymer surfaces have not been directly grafted with phosphate groups by chemical reactions because the usual organic solvents used to graft phosphate groups can dissolve or swell polymers. We focused this study on grafting phosphate groups onto a poly(ethylene-co-acrylic acid) (PEAA) surface in an aqueous solution. O-phospho L-serine and O-phosphoethanolamine were grafted on PEAA surfaces to introduce phosphate groups by activating carboxylic acid groups of PEAA using N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in an aqueous environment. X-ray photoelectron spectroscopy (XPS) was used to elucidate the process by which surface grafting occurs and the process that the phosphate group is cleaved into a phosphate ion and a hydrolyzed molecule at high pH. It was found that under appropriate reaction conditions the phosphate groups could be successfully grafted on the polymer surfaces. The phosphate-grafted polymer surfaces showed lower water contact angles than the initial polymer surfaces likely due to their highly mobile and hydrophilic phosphate side groups. This work demonstrates a technique to successfully graft phosphate groups onto organic polymer surfaces in a biocompatible aqueous environment, which may open new avenues to functionalizing synthetic polymeric and natural macromolecule derived biomaterials.     

The eosin-sensitized photooxidation of substituted phenylalanines and tyrosines.

Abstract— The eosin-sensitized photooxidation of tyrosine and a number of compounds related to tyrosine (substituted phenylalanines) was studied by steady-state kinetic and flash photolysis techniques. In particular, the role of the phenolic group and the amino and carboxyl groups of the alanyl side chain in the photooxidation mechanism was investigated in detail. Several relationships between substrate structure and susceptibility to photooxidation as well as effects of substrate structure on photooxidation mechanisms were found. For example, phenylalanine is not photooxidizable, hut substitution of electron-donating (activating) groups such as-OH (as in tyrosine) or-NH₂ (as in p-aminophenylalanine) results in rapidly photooxidized derivatives. However, substituting deactivating groups such as—C1 (as in p-chlorophenylalanine) or weakly activating groups such as - OCH₃ (as in 4-methoxyphenylalanine) result in non-photooxidiz-able derivatives. Substitution of additional activating groups to the ring of hydroxy-substituted phenylalanines results in increased rates of photooxidation, whereas additional deactivating groups result in decreased photooxidation rates. The rate-determining step in the photooxidation mechanism is shown to be dependent on the presence and position of an electron-donating substituent on the benzenoid ring. Only minor involvement of the side chain amino and carboxyl groups was found. Both singlet oxygen and hydrogen abstraction mechanisms are involved in the eosin-sensitized photooxidation of hydroxy-substituted phenylalanines (e.g. tyrosine). The hydrogen abstraction mechanism probably predominates at both pH 8 and 11.     

The definition of the toxicologically relevant applicability domain for the SNAr reaction for substituted pyridines and pyrimidines

This study outlines how results from a glutathione reactivity assay (so-called in chemico data) can be used to define the applicability domain for the nucleophilic aromatic substitution (S_NAr) reaction for nitrogen-containing aromatic compounds. S_NAr is one of the six mechanistic domains that have been shown to be important in toxicological endpoints in which the ability to bind covalently to a protein is a key molecular initiating event. This study has analysed experimental data (2 h RC₅₀ values), allowing a clear and interpretable structure–activity relationship to be developed for pyridines and pyrimidines which reside within the S_NAr domain. The in-ring nitrogen(s) act as activating groups in the S_NAr reaction. The position(s) of the in-ring nitrogen(s) as well as other activating groups, especially in relationship to the leaving group, affect reactive potency. The experimentally defined applicability domain has resulted in a series of structural alerts. These results build on early work on the benzene derivatives residing in the S_NAr domain. The definition of the applicability domain for the S_NAr reaction and the resulting structural alerts are likely to be beneficial in the development of computational tools for category formation and read-across in hazard identification, and the development of adverse outcome pathways.     

Characterization of chromodulin by X-ray absorption and electron paramagnetic resonance spectroscopies and magnetic susceptibility measurements

The biologically active form of the essential trace element chromium is believed to be the oligopeptide chromodulin. Chromodulin binds four chromic ions before binding at or near the active site of activating insulin receptor and subsequently potentiating the tyrosine kinase activity of the receptor. Charge balance arguments and preliminary spectroscopic studies suggested that the chromic centers might be part of a multinuclear assembly. Using a combination of X-ray absorption and electron paramagnetic resonance spectroscopies and variable-temperature magnetic susceptibility measurements, we found that holochromodulin is shown to possess an antiferromagnetically coupled trinuclear assembly which probably weakly interacts with a fourth chromium center. The chromium centers possess octahedron coordination comprised of oxygen-based ligation, presumably derived primarily from oligopeptide-supplied carboxylate groups. X-ray absorption data cannot be reproduced with the presence of sulfur atom(s), indicating that the cysteine thiolate group does not coordinate to the chromium centers. Thus, chromodulin possesses a unique type of multinuclear assembly, distinct from those known in other bioinorganic systems.     

High-temperature reactions of hydroxyl and carboxyl PET chain end groups in the presence of aromatic phosphite

When melt-extruded in the presence of triphenylphosphite (TPP), the molecular weight of polyesters such as poly(ethylene terephthalate) (PET) increases with time. Analysis of the PET chain end groups and model studies of high-temperature reactions indicate that, most likely, the process leading to chain extension of PET in the presence of TPP takes place in two steps. In the first step, TPP rapidly reacts with the hydroxyl end groups by displacing one phenoxy group from the TPP. In the second step, a slow reaction takes place between the alkyldiphenyl phosphite and carboxylic chain end groups, forming an ester bond between the carboxyl and alkyl groups, and producing diphenylphosphite (DPP) as a reaction by-product. The DPP tautomerizes to its pentacovalently bonded stabler form of diphenylphosphate, the form in which the DPP was usually detected in our analyses. The ester formation results in the extension of the PET chains. Model studies are presented which support the proposed mechanism.     

Ortho selectivity in SNAr substitutions of 2,4-dihaloaromatic compounds. Reactions with piperidine

A broad survey of aromatic compounds with halogens positioned both ortho and para to activating groups was studied in S_NAr reactions with piperidine. Regioselectivities varied with the substituent group and the polarity of the solvent. Many activating groups exhibited an overall bias toward ortho-substitution, and this led in nonpolar solvents to very high ortho selectivity. More polar solvents uniformly shifted the product ratio toward para substitution. Evidence is presented that argues for coordination via hydrogen bonding as a driver of much of the ortho selectivity observed. The data presented show ample evidence of the generality and synthetic utility of the ortho-directing ability of several common activating groups for this reaction type.     

Chiral NMR discrimination of piperidines and piperazines using (18-crown-6)-2,3,11,12-tetracarboxylic acid

Enantiomeric discrimination is observed in the (1)H and (13)C NMR spectra of piperidines and piperazines in the presence of (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. The amines are protonated by the carboxylic acid groups of the crown ether to produce the corresponding ammonium and carboxylate ions. Association of the ammonium ion with the crown ether likely involves two hydrogen bonds with the crown ether oxygen atoms and an ion pair with the carboxylate anion. Methyl, hydroxymethyl, phenyl, carboxyl, pyridyl, and cyclohexyl substituent groups alpha to the nitrogen atom do not inhibit binding of the ammonium ion to the crown ether. The NMR spectra of piperidines with the stereogenic center alpha or beta to the nitrogen atom exhibit substantial enantiomeric discrimination. Dibasic substrates such as the piperizines are likely converted to their diprotonated form in the presence of the crown ether, and both nitrogen atoms appear to associate with the crown ether moiety.     

On the electron donor and the electrophilic substitution activating abilities of substituents in uracil

QTAIM properties for uracil and 18 derivatives containing the substituents -NH(2), -OH, -OCH(3), -SH, -F, -Cl, -CH(3) -NO(2), and -Li in position 5 or 6 were computed on MP2/6-31++G//MP2/6-31G charge densities. The results indicate that -OH, -OCH(3), and -NH(2) groups are really retrieving charge from the ring. Also, the activating ability of the substituent groups, usually considered as the variation of electron population at the carbon where the electrophilic attack takes place, C, was studied. The study shows that the activating ability is reflected by the variation of pi charge or quadrupole moment at C, and also by the variation of the Laplacian of the charge density in the secondary charge concentration points around C (SCC-C). They indicate a similar, but not exactly equal, graduation of activating ability. The relative behavior of the substituents is basically the same as in benzene, though benzene has more tendency to concentrate charge in the SCC-C regions than uracil, where this tendency is larger for 6- than for 5-derivatives. sigma(+/-)(R) Taft parameters are found to display good correlations with the above indicated activating indexes. Finally, the resonance model predicts most of the main variations displayed by QTAIM atomic pi electron populations of derivatives with regard to uracil, but there are still some significant variations of the pi electron charge that it cannot predict.     

Palladium-catalyzed synthesis of aryl ketones by coupling of aryl bromides with an acyl anion equivalent

Palladium-catalyzed couplings of aryl bromides with N-tert-butylhydrazones as acyl anion equivalents to form aryl ketones are reported. The coupling process occurs at the C-position of hydrazones to form N-tert-butyl azo compounds. Isomerization of these azo compounds to the corresponding hydrazones, followed by hydrolysis, gave the desired mixed alkyl aryl ketones. The selectivity of C- versus N-arylation was strongly influenced by the substituent on nitrogen. Arylation at carbon occurred with N-tert-butylhydrazones, whereas N-arylation occurred with N-arylhydrazones. The arylation of hydrazones containing primary and secondary alkyl groups, as well as aryl groups, gave the desired ketones in good yields after hydrolysis. Functional groups on the aromatic ring, such as alkoxy, cyano, trifluoromethyl, carboalkoxy, carbamoyl, and keto groups, were tolerated. This reaction likely occurs by C-C bond-forming reductive elimination from an intermediate containing an eta1-diazaallyl ligand.     

Efficient synthesis of protein-drug conjugates using a functionalizable recombinant elastin-mimetic polypeptide

This report describes the efficient conjugation of doxorubicin-glycine-phenylalanine-leucine-glycine (1a) and rhodamine-glycine-phenylalanine-leucine-glycine (1b) units to a monodisperse elastin-mimetic polypeptide (EMM)(7) bearing eight primary amine groups for chemical attachment. The synthetic approach is based on the solid-phase synthesis of 1a and 1b followed by chemical conjugation to the elastin-mimetic polypeptide in the presence of HOBt/PyBob as activating agents to form the polypeptide conjugates 2a and 2b. Conjugation efficiency was 61.2% (4.9 doxorubicin units per polypeptide chain) for 2a and 53.7% (4.3 rhodamine units per polypeptide chain) for 2b, demonstrating the feasibility of using these tailor-made, recombinant polypeptides as potential drug carriers for cancer therapy.     

1H- and 13C-NMR. Studies of the molecular conformations of cyclo-tetraglycyl.

The ¹H- and ¹³C-NMR. spectra of cyclo-tetraglycyl show that the four peptide groups are magnetically equivalent, and different from either a standard trans or a standard cis peptide group. It is suggested that the observed NMR. features correspond to a non-planar form of the peptide groups. On the one hand these data confirm the earlier conclusions from theoretical investigations of the molecular geometry, that cyclic tetrapeptides could not contain four standard trans peptide groups. On the other hand they are not consistent with a previously suggested alternative molecular conformation according to which cyclo-tetraglycyl would adopt a conformation similar to cyclo-tetrasarcosyl, with two cis and two trans peptide bonds. The different behaviour of glycine and sarcosine under the steric strains of tetrapeptide ring closure would appear to suggest that with the exception of the X-Pro bonds, transoid peptide groups in polypeptide chains of the common amino acids should be more likely to occur than the cis form, which has as yet apparently not been observed for N-unsubstituted peptide groups in natural peptides or proteins.     

Total Synthesis of Chatancin

As an antagonist of the platelet activating factor , chatancin ( 1 ), which is isolated from a soft coral, is of potential therapeutic use. The first total synthesis [Eq. (1)] of this structurally unusual diterpene in racemic form is described along with the formal total syntheses of natural (+)-chatancin as well as unnatural (−)-chatancin.     

On orthogonal and selective activation of glycosyl thioimidates and thioglycosides: application to oligosaccharide assembly

Discrimination among S-thiazolinyl (STaz), S-benzoxazolyl (SBox), and S-ethyl anomeric leaving groups was achieved by fine-tuning activation conditions. Preferential glycosidation of a certain leaving group is determined neither by the strength of the activating reagent nor by the stability of the leaving group itself; instead, the type of activation plays the key role. The activation conditions established herein were applied to a sequential five-step synthesis of a hexasaccharide using six monosaccharide building blocks equipped with six different leaving groups.     

末端带有溴甲基基团的柱状树枝化聚酰胺的合成与表征

采用大分子单体的方法合成了一种含大量溴甲基官能团端基,主链和侧链均为聚酰胺的功能化柱状树枝化聚酰胺.氯化亚砜的新活化工艺使整个合成过程不需要保护和去保护的步骤且减少了副反应的产生,从而使得合成和纯化更加简单.产物的结构通过红外和核磁得到了证实.由分子量测试知,聚酰胺的重均分子量(Mw)为5.01×104,分子量分布为2.74.由溶解性测试知,该聚合物能溶解于N,N′-二甲基甲酰胺、N,N′-二甲基乙酰胺、二甲亚砜、1-甲基-2-吡咯烷酮和硫酸等溶剂,溶解性能得到了大大的提高,主要是由于侧链树枝化单元和末端溴甲基存在的缘故.由粘度测试知,该聚酰胺的粘度低,主要是由于侧链树枝化单元的屏蔽效应.该聚合物的热性能也由TGA测试得到了表征,结果表明该聚酰胺具有良好的热性能.由于该聚酰胺外端具有大量的溴甲基基团,它可以作为原子转移自由基聚合反应的引发剂来合成大型的梳形聚合物,另外通过把它外围的溴甲基转化为其它的功能化基团,可以使它应用于其它更广的领域.     

Synthesis,IR Spectra,and Steric Structure of Macrocycles Derived from Pyrimidine Compounds

A new macrocycle including pyrimidine fragments, 12,23,36-trimethyl-24,40-dioxo-15,33-dithia-2,9,13,22,26,35,38,39-octaazatetracyclo[32.3.1.110,14.122,26]tetraconta-1(38),10(39),11,13,23,34,36-heptaene, was synthesized. According to the data of IR and UV spectroscopy and HF/6-31G** quantum-chemical calculations, macrocyclic compounds of this series in crystal exist in the amino form, one NH group of which is likely to be involved in intramolecular hydrogen bond, and the other, in intermolacular hydrogen bond. The strength of the latter depends on the macroring size. In solution, the above structures are supplemented by conformers containing both intramolecularly H-bonded and free amino groups, predominantly with trans structure of the HÄNÄCÍN fragment. The imino form of the aminopyrimidine moieties is hardly probable.