Reaction sequence searching

A reaction sequence search system needs to be able to find sequences in reaction schemes and also sequences involving implicit links between individual reaction steps either in schemes or individually stored reaction entries. The user may wish to indicate when defining a search the maximum number of reaction steps in a sequence and whether implicit links can be used in the search. We are currently extending the Reaction Search facility in ORAC to provide such facilities. One major problem that must be overcome is the ability to transfer mapping information relating the reactant and product structures for each reaction in a... 

The final chapters cover other aspects of chemical reaction handUng. Josef Brandt of the Technical University of Munich describes a tool for coding cychsation reactions Dan Meyer of ART Inc, and his co-workers, have studied chemical reaction retrieval using citation-based relationships Glen Hopkinson and others at ORAC write about reaction sequence searching and Brad Christie and Tom Moock of Molecular Design Limited discuss multistep reaction schemes in REACCS. 

The search for low-molecular weight (phenoxyl)copper(II) complexes as functional models for GO, which would mimick this reactivity, had a promising start in 1996 when Tolman and co-workers (202) reported that electrochemical one-electron oxidation of Cull(,L,lil 2)(bcnzylalcoholatc) (Fig. 27) resulted in the formation of benzaldehyde (46%) and some other decomposition products of the ligand H L,Bu2 in <5% yield and probably a Cu(I) species of unknown composition. These authors suggest that a (phenoxyl)copper(II) intermediate Cull(,L,l l 2 )(bcn-zylalcoholate)]+ is formed and that the reaction sequence, as in Fig. 8, leads to the observed products. Although this represents a stoichiometric reaction, it demonstrated for the first time that GO chemistry can be successfully modeled. 

Search the Internet for kinetic parameters of jS-fructosidase and a-galactosidase. Perform metabolic simulation to compare the effectiveness of the two reaction sequences to produce D-glucose. 

The question remains open as to whether the surface complexes as proposed in (36)- (39) can be formed under FT conditions, especially at the higlt temperatures and (he low- CO partial pressures used [4], The search for surface chemisorbed formyl species has been unsuccessful 1114], Tlius, the interaction of formaldehyde, glyoxa) and CO/Hj with Al Oi supported rhodium gave no IR-detectahle traces of formyl species [ 169]. The insertion mechanism proposed by Hcnrici-Oliv and Olive is closely related to the Pichler Schul/. mechanism [40]. A reaction sequence based on the oxidative addition of hydrogen and reductive elimination of water is assumed Only one metal center is required, however, the mechanism of water elimination is not explained in detail,... 

It is apparent, then, that precursors for terminal vinyl azides are obtained following iodine azide addition to olefins only when rather unusual steric or electronic factors are operating. A number of other reaction sequences have been investigated in the search for a general approach to the terminal compounds. The opening of a terminal epoxide by azide ion leads to an azidohydrin which can be readily dehydrated (equation 4). Unfortunately, this reaction sequence... 

SOLUTION The most straightforward way to optimize a function is by a brute-force search. Code for Example 6.3 does this using subroutines developed in Code for Example 6.2. Results from such a search are shown in Table 6.2. The example reaction sequence shows a board range of values for T and V that give close to the minimum cost. The engineer should rejoice. Since the cost is relatively insensitive to the design choices, decisions should be reasonable despite model error. 

Schemes 9-3 and 9-4 are sequences of two substitutions, first a metallo-de-hydrogenation, followed by a halogeno-de-metallation. Scheme 9-3 is analogous to the well known electrophilic aromatic sulfonation of anthraquinone in position 1. This isomer is obtained only if the reaction is run in the presence of catalytic amounts of mercury (ii) salts. Nowadays, however, larger effort is devoted to either replace mercury by other catalysts, or in the search for processes leading to (practically) complete recovery of the mercury. This case raises two questions with respect to the reaction sequence (9-3) first, whether it is possible to apply a one-pot process with catalytic amounts of a mercury compound (not necessarily HgO) to the synthesis of compounds 9.5, and second, whether mercury can be completely recycled in processes using either stoichiometric or catalytic amounts of the element.

Reaction retrieval deals with very precise full structure information but you have to be aware of different possible ways to define the reaction centres. Another problem is the various notations for certain functional groups (e.g., sulphur and phosphorus groups). The most restricting factor yet is the inability to search for reaction sequences. Because of this you have to guess how a one-pot reaction or a multistep sequence was stored in the database. As a consequence you miss the information (Figure 6). 

This model of concept number syntax can be applied to the representation of many other relations between concepts. To do this one needs only assign distinct concept numbers to the concepts in a document and to represent the interesting relation between the concepts in a correspondingly defined logical formula. In this way, for example, one can express the relations between the components of a pharmaceutical preparation or the type of relation that prevails among the compounds that belong to the same reaction sequence. The exclusion of a specific component in a composite can also be phrased as a search parameter. 

Each level has its merits. The "ab initio" level is useful for discovering new reactions by searching for new sequences of electron pushing steps. The "name-reaction" level is most useful for novel total synthesis whereas the "reaction sequence" level is useful for rapidly generating classical syntheses, but has little innovative power. 

In chemical synthesis the goal state is the target molecular structure and the operators to consider for constructing a solution sequence are molecular reactions. The search for a synthesis plan proceeds backwards from the target molecular structure by considering and applying reactions in the retro-synthetic direction. The process is a serial one and has an "inner loop" that repeatedly asks... 

Recently, multistep enzyme-catalyzed reactions have attracted the attention of chemists and biotechnologists, as they can be combined in a modular manner and often lead to high-value compounds. All naturally occurring metabolic pathways are basically cascade reactions. Based on natural principles, synthetic chemists search for universal multistep processes applicable to a vast number of chemical compounds. Multistep enzyme-catalyzed reactions involving nonphysiological substrates and selective enzymes are of particular interest because they may lead to tailor-made complex molecules with desired properties. Moreover, one of the most important advantages of multistep enzyme-catalyzed reaction sequences... 

In this paper we describe how the ORAC reaction database system has been integrated with the LHASA synthesis planning program. This interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved from ORAC and displayed to the user. The problem of sequence searching in reaction database systems is also explored and approaches to this problem are described. Finally, the potential use of synthesis planning systems to identify and classify links between reactions in ORAC for use during sequence searching is considered. 

Reaction database systems need to be able to store reaction schemes and search for reaction sequences involving both explicit schemes and implicit links between individual reactions in a database. A third class of links between reactions has been defined which involves identifying the presence of the reacting environment of one reaction in the product of another synthesis design programs could prove useful in classif3dng and indexing such linl. ... 

This paper describes a feasibility and prototyping study of multi-step reaction sequence representation and searching, using REACCS as a starting point. The results of this study will show the benefits and costs of a few alternatives, and the utility of such a system in the hands of practising synthetic chemists. Detailed studies were carried out on probable architectures of systems which support Explicit- and First-Order Implicit schemes options for the support of Second-order Implicit schemes are described in theoretical terms only. 

Any program that can be used to find implicit schemes will also find explicit schemes. The added value of a search over implicit schemes will be based on the number of additional answers an implicit search provides, which in general is determined by the number of independent reactions sharing common molecules. The diversity of the chemistry, the unusualness of the molecules, and the ratio of reactions to molecules in the database will all have an effect on the volume of results of implicit sequence searches. 

Figure 9. Illustration of search-time discovery of reaction sequences. A breadth-first search is used to find a pathway of molecules linking the reactant hit list to the product hit list...

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