Chemical markup,XML, and the World Wide Web. 4. CML schema

A revision to Chemical Markup Language (CML) is presented as a XML Schema compliant form, modularized into nonchemical and chemical components. STMML contains generic concepts for numeric data and scientific units, while CMLCore retains most of the chemical functionality of the original CML 1.0 and extends it by adding handlers for chemical substances, extended bonding models and names. We propose extension via new namespaced components for chemical queries, reactions, spectra, and computational chemistry. The conformance with XML schemas allows much greater control over datatyping, document validation, and structure.     

Chemical markup, XML and the World-Wide Web. 3. Toward a signed semantic chemical web of trust

We describe how a collection of documents expressed in XML-conforming languages such as CML and XHTML can be authenticated and validated against digital signatures which make use of established X.509 certificate technology. These can be associated either with specific nodes in the XML document or with the entire document. We illustrate this with two examples. An entire journal article expressed in XML has its individual components digitally signed by separate authors, and the collection is placed in an envelope and again signed. The second example involves using a software robot agent to acquire a collection of documents from a specified URL, to perform various operations and transformations on the content, including expressing molecules in CML, and to automatically sign the various components and deposit the result in a repository. We argue that these operations can used as components for building what we term an authenticated and semantic chemical web of trust.     

Chemical Markup, XML, and the World Wide Web. 7. CMLSpect, an XML vocabulary for spectral data

CMLSpect is an extension of Chemical Markup Language (CML) for managing spectral and other analytical data. It is designed to be flexible enough to contain a wide variety of spectral data. The paper describes the CMLElements used and gives practical examples for common types of spectra. In addition it demonstrates how different views of the data can be expressed and what problems still exist.     

Chemical Markup, XML and the World-Wide Web. 8. Polymer Markup Language

Polymers are among the most important classes of materials but are only inadequately supported by modern informatics. The paper discusses the reasons why polymer informatics is considerably more challenging than small molecule informatics and develops a vision for the computer-aided design of polymers, based on modern semantic web technologies. The paper then discusses the development of Polymer Markup Language (PML). PML is an extensible language, designed to support the (structural) representation of polymers and polymer-related information. PML closely interoperates with Chemical Markup Language (CML) and overcomes a number of the previously identified challenges.     

Chemical markup, XML, and the World Wide Web. 5. Applications of chemical metadata in RSS aggregators

Examples of the use of the RSS 1.0 (RDF Site Summary) specification together with CML (Chemical Markup Language) to create a metadata based alerting service termed CMLRSS for molecular content are presented. CMLRSS can be viewed either using generic software or with modular opensource chemical viewers and editors enhanced with CMLRSS modules. We discuss the more automated use of CMLRSS as a component of a World Wide Molecular Matrix of semantically rich chemical information.     

Chemical markup, XML and the World-Wide Web. 2. Information objects and the CMLDOM

We describe the development of a structured method of representing chemistry on the World-Wide Web using an object-oriented approach to information objects. We show how a document object model (DOM) for chemistry can be constructed using as its basis Chemical Markup Language (CML). Application of the CMLDOM to the development of chemical tools is described.     

Ontology aided modeling of organic reaction mechanisms with flexible and fragment based XML markup procedures

The mechanism models for primary organic reactions encoding the structural fragments undergoing substitution, addition, elimination, and rearrangements are developed. In the proposed models, each and every structural component of mechanistic pathways is represented with flexible and fragment based markup technique in XML syntax. A significant feature of the system is the encoding of the electron movements along with the other components like charges, partial charges, half bonded species, lone pair electrons, free radicals, reaction arrows, etc. needed for a complete representation of reaction mechanism. The rendering of reaction schemes described with the proposed methodology is achieved with a concise XML extension language interoperating with the structure markup. The reaction scheme is visualized as 2D graphics in a browser by converting them into SVG documents enabling the desired layouts normally perceived by the chemists conventionally. An automatic representation of the complex patterns of the reaction mechanism is achieved by reusing the knowledge in chemical ontologies and developing artificial intelligence components in terms of axioms.     

Detailed mechanism generation. 2. Aldehydes, ketones, and olefins

Generalized reaction classes for the consumption and decomposition of aldehydes, ketones, and olefins are described. These classes are important for generating not only reactions for the consumption of the branching agents of low-temperature hydrocarbon combustion but also reactions of the oxidation of alkenes and the decomposition of cyclic ethers. These reaction classes have been extrapolated from specific reactions of existing validated mechanisms. The reaction patterns making up the class were derived by identifying the reactive center of the specific reactions and the important surrounding functional groups. The rates used currently are definitely "first guesses" based on these specific reactions. The reaction classes in this paper supplement the reaction classes derived from accepted reaction types in the previous paper in this series. The purpose of this paper is to outline a complete (with very few exceptions) set of reaction classes which describe the C(5) and C(6) products of the low-temperature and cyclic ether path in the heptane and isooctane mechanisms.     

Organogermyl,Organostannyl, and Organoplumbyl Phosphines,Arsines, Stibines,and Bismuthines

The preparation, properties, and reactions of the compounds named in the title are described, with particular reference to the possible participation of (p→d)_π components in the bonding between the group IVB and the group VB elements.     

Byproduct‐Catalyzed Four‐Component Reactions of Aldehydes with Hexamethyldisilazane,Chloroformates, and Nucleophiles in Acetonitrile Leading to Protected Primary Amines, β‐Amino Esters,and β‐Amino Ketones

Multicomponent reactions are a very powerful tool for the construction of complex organic molecules by using readily available starting materials. While most of the multicomponent reactions discovered so far consist of three components, the reactions with four or more components remain sparse. We have successfully developed several four‐component reactions using a catalytic amount of water as a hydrolyzing agent to decompose byproduct chlorotrimethylsilane (TMSCl) to yield secondary byproduct HCl that serves as a catalyst. In the presence of 40 mol % of water, the four‐component reaction of aldehydes with hexamethyldisilazane (HMDS), chloroformates, and silylated nucleophiles proceeds smoothly at room temperature to give a range of protected primary amines in moderate to excellent yields. Importantly, a wide variety of protic carbon nucleophiles, such as β‐keto esters, β‐diketones, and ketones, have further been explored as suitable substrates for the synthesis of protected β‐amino esters and β‐amino ketones that are useful building blocks for various pharmaceuticals and natural products. These four‐component reactions proceed through a pathway of tandem nitrogen protection/imine formation/imine addition, and the decomposition of byproduct TMSCl, generated in the first step of nitrogen protection, with water results in the formation of secondary byproduct HCl, a strong Brønsted acid that catalyzes the following imine formation/imine addition. Taking advantage of the fact that alcohols or phenols are also able to decompose byproduct TMSCl to yield secondary byproduct HCl, no catalyst is needed at all for the four‐component reactions with aldehydes bearing hydroxy groups.     

Relative energy of organic compounds III. Components of the heat of reactions

The relative enthalpies of organic compounds described in Parts I and II of this series made possible to show the contribution of the reactants and products to the heat of reactions. First, the meaning of the relative enthalpies is demonstrated. The components of the heats of reactions are exemplified by a series of reactions: formation of alkyl halides, esters, amides, acid halides, and anhydrides. Further examples are hydrogenation of alkenes, alkynes, benzene, ethylene oxide, aldehydes, and nitriles, and addition of chlorine, water, and hydrogen chloride to ethylene. Acetal and hemiacetal formations and cyclization reactions are also among the examples.     

Silyl glyoxylates. Conception and realization of flexible conjunctive reagents for multicomponent coupling

This Perspective describes the discovery and development of silyl glyoxylates, a new family of conjunctive reagents for use in multicomponent coupling reactions. The selection of the nucleophilic and electrophilic components determines whether the silyl glyoxylate reagent will function as a synthetic equivalent to the dipolar glycolic acid synthon, the glyoxylate anion synthon, or the α-keto ester homoenolate synthon. The ability to select for any of these reaction modes has translated to excellent structural diversity in the derived three- and four-component coupling adducts. Preliminary findings on the development of catalytic reactions using these reagents are detailed, as are the design and discovery of new reactions directed toward particular functional group arrays embedded within bioactive natural products.     

Pyrolysis of aminonitriles,cyanohydrazones, and cyanoacetamides. Part II. Elimination reactions of arylacetylhydrazone,arylcyanoacetylhydrazone, and substituted cyanoacetamides

Rates of pyrolytic reactions of arylacetylhydrazone and arylcyanoacetylhydrazone (1–4) of the general formula GCH₂CONHNCHAr (G = H,CN) have been measured. The increase in the acidity of the hydrogen atom involved in the six-centered elimination process suggested for these reactions causes a significant increase in rates and thus appears to be the limiting factor in these pyrolytic reactions. The implication of this conclusion for the pyrolytic reactions of substituted cyanoacetamides (5–8), NCCH₂CONHAr are considered. The mechanism of pyrolytic reactions of compounds (5–8) appears to proceed through a 4-membered cyclic transition state. © 1996 John Wiley & Sons, Inc.     

Highly efficient one-pot synthesis of N-sulfonylamidines by Cu-catalyzed three-component coupling of sulfonyl azide, alkyne, and amine

A highly efficient, mild, practical, and catalytic multicomponent reaction for the synthesis of N-sulfonylamidines has been developed. This reaction has an extremely wide scope with regard to all three coupling components of alkyne, sulfonyl azide, and amine. Two plausible mechanistic pathways involving ketenimine or triazole intermediate are tentatively presented for the copper-catalyzed three-component coupling reactions.     

Identification of the carboxymethyllysine residue in the advanced stage of glycated human serum albumin.

As an advanced stage of glycation, glycated human serum albumin (G-HSA; glucose content, 2 mol of 5-hydroxymethylfurfural equivalent/mol of HSA) was incubated at 37 degrees C up to 30 d in 0.2 M phosphate buffer, pH 7.4, with 100 microM Fe3+. G-HSA incubated for 30 d (G-HSA-30(Fe)) was subsequently hydrolyzed at 110 degrees C for 24 h in 6 N HCl. In the hydrolysate, N epsilon-carboxymethyllysine (CML) was identified by cochromatography with synthesized CML on an amino acid analyzer. pI of HSA (4.8) shifted to 4.5 in G-HSA. A more acidic fraction, pI 4.3, appeared in G-HSA-30(Fe). CML content (mol of CML/mol of HSA) of HSA and G-HSA was as follows; 0 in HSA, 0.2 in HSA-30(Fe), 0.4 in G-HSA and 1.5 in G-HSA-30(Fe) pI 4.3. The amino acid compositions also changed in lysine, arginine and tyrosine at the advanced stage of the reaction.     

Hydroxypyrimidines Condensation with Carbonyl Compounds: II. Hydroxy-, Sulfanyl-, and Aminopyrimidines

The first part of review treated condensation of barbituric acids with carbonyl compounds both in the absence and in the presence of third components [1]. In so doing we discussed only the reactions involving the C ⁵ atom of the pyrimidine ring. The second part concerns similar transformations of other hydroxy- and aminopyrimidines and thioanalogs thereof.     

Chemical reactions in microdroplets and microbubbles. Thermodynamic approach

In small dispersed systems, the standard chemical potential of the components present in the curved phases is different from the one in phases with a flat interface. Thermodynamic properties of reactions in such systems, at mechanical equilibrium, may be different from those for the same reactions at the same temperature, in a phase with zero curvature. Among these properties, we study here the dependence of the equilibrium constant on the curvature, on the surface tension and on the stoichiometry of the process. Reactions in an electric field are also discussed.     

Transition metal-catalyzed cyclocarbonylation in organic synthesis

Cyclocarbonylation reactions proceed mainly by the coupling reactions of carbonylation components with cyclization components having an unsaturated π-electron bond, in the presence of transition metal compounds. The representative reactions are cyclocarbonylation of alkynes by carbon monoxide such as Pauson–Khand reactions, hetero Pauson–Khand reactions, cyclocarbonylation of alkynyl alcohols, cyclocarbonylation of alkynyl amines, cyclocarbonylative alkyne–alkyne coupling reactions, and reductive cyclocarbonylation of alkynes. The other reactions are cyclocarbonylation of alkenes by carbon monoxide such as alkene–alkene coupling reactions, cyclocarbonylation with aldehydes, ketones, amines or imines, cyclocarbonylation of alkenyl alcohols. Carbonylation via cyclometalation, carbonylative ring expansion reactions, cyclocarbonylation by aldehydes, carboxylic acids or carboxylic acid esters are also cyclocarbonylation reactions. These reactions are conveniently used for organic syntheses, especially, for the syntheses of pharmaceutical intermediates.     

Selective iron-catalyzed cross-coupling reactions of grignard reagents with enol triflates, acid chlorides, and dichloroarenes

Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)(3) are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n) generated in situ. Control experiments using the ate-complex [Me(4)Fe]Li(2) corroborate this interpretation.     

The proline-catalyzed direct asymmetric three-component Mannich reaction: scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols

We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide beta-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.