EROS

The synthetic design program EROS and its predecessors generate a tree of BE-matrices starting from one BE-matrix which refers to the synthetic target. This tree may be interpreted as a tree of synthetic pathways. 

ACS Symposium Series American Chemical Society Washington, DC, 1977. 

The mathematical model affords also entirely different approaches to chemical problems. If the initial and final ensemble of molecules, EM(B) and EM(E), of a chemical reaction, or a sequence of reactions are known, or attained by an educated guess, such as a comparison of substructures (see section 5.1-3) the difference of the corresponding BE-matrices E-B = R can be analyzed to yield the pathways of individual steps which lead from EM(B) to EM(E). These pathways may be sequences of intermediates in a reaction mechanism, or also sequences of synthetic intermediates. The precondition for this approach is that the indices of the atoms in EM(B) and EM(E) are appropriately assigned. The required assignment of atomic indices is discussed in section 5 3 1) All of these applications of the mathematical model, as well as the search of BE-matrix pairs (B, E) which fit a given R-matrix will be contained in MATCKEM. 

In the now following sections some recently implemented parts of MATCHEM will be presented. 

A precondition for an efficient manipulation of BE-matrices in the computer is a canonical indexing of the atoms in a molecule. In order to generate a unique numbering we use the connectivity matrix of the molecular graph and the labels already assigned to its vertices, i.e. the chemical symbols. 

The knowledge base is essentially two-fold on one hand it consists of a series of procedures for calculating all-important physicochemical effects such as heats of reaction, bond dissociation energies, charge distribution, inductive, resonance, and polarizability effects (.see Section 7.1). The other part of the knowledge base defines the reaction types on which the EROS system can work. 

After the definition of a reaction type, a scheme for the evaluation of the given reaction type can follow in the reaction rule. An entire hierarchy of evaluations can be implemented, from no evaluation at all to a full-fledged estimation of reaction kinetics [12  

Clearly, in this case, checks have to be made whether a specific isomer has already been produced by a different pathway. This is achieved by the calculation of hashcodes (see Section 2.7.4). 

The reaction type for the generation of all ison reric alkat nes of a given r 

More elaborate scheme.s can he envisaged. Thus, a. self-organizing neural network as obtained by the classification of a set of chemical reactions as outlined in Section 3,5 can be interfaced with the EROS system to select the reaction that acmaliy occurs from among various reaction alternatives. In this way, knowledge extracted from rcaetion databases can be interfaced with a reaction prediction system, 

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Clearly, for symmetry reasons, the reverse process should also be considered. In fact, early versions of our reaction prediction and synthesis design system EROS [21] contained the reaction schemes of Figures 3-13, 3-15, and 3-16 and the reverse of the scheme shown in Figure 3-16. These four reaction schemes and their combined application include the majority of reactions observed in organic chemistry. Figure 3-17 shows a consecutive application of the reaction schemes of Figures 3-16 and 3-13 to model the oxidation of thioethers to sulfoxides. 

Two systems will be introduced below on the one hand the DENDRAL system for automatic structure elucidation [25], which was one of the first expert systems on the other hand the EROS system [26], which can be used for simulating reactions. 

The EROS (Elaboration of Reactions for Organic Synthesis) system [26] is a knowledge-based system which was created for the simulation of organic reactions. Given a certain set of starting materials, EROS investigates the potential reaction pathways. It produces sequences of simultaneous and consecutive reactions and attempts to predict the products that will be obtained in those reactions. 

Two systems, CAMEO and EROS, have been developed that approach the task of reaction prediction in a broad and comprehensive manner. Both systems were initiated around 1975 and are presented in more detail in Sections 10.3.1.4 and 10.3.1.5. 

The most recent version of EROS has a clearcut separation of the system proper, which performs all the manipulations on chemical structures and reactions, from the knowledge base, which defines the scope of it.s application (Figure 10.3-7). 

Heats of reaction Heats of reaction can be obtained as differences between the beats of formation of the products and those of the starting materials of a reaction. In EROS, heats of reaction arc calculated on the basis of an additivity scheme as presented in Section 7.1. With such an evaluation, reactions under thermodynamic control can be selected preferentially (Figure 10.3-10). 

It has already been mentioned that the degradation of s-triazine herbicides such as atrazinc in soil can be described by two reaction types only, hydrolysis and reductive dealkylation (see Figure 10.3-8). Application oF these two reaction types to a specific s-triazinc compound such as atrazinc provides the reaction network shown in Figure 10,3-12. This can also be vcriFicd by running this example on h ttp //www2,chemie,uni-erlangen.de/semces/eros/,... 

When the cutoff is sharp, discontinuities in the forces and resultant loss of con servation of energy m molecular dynamics calcnla-tionscan result.To minimi/e edge effects of a cu toff, often theciit-off IS implemented with a switching or shifting function to allow the interactions to go smoothly to /ero. 

Hetween the inner radius R, of the switch and the outer radius of the switch the mieractioii goes smooth ly to /.ero. HyperChern uses as its default an in a er radius of I 0 A an d an outer radius of 14 A. 

In the cooling phase (assuming t. is non-/ero), the velocities are periodically rescaled to change the system temperature from the run temperature to the final temperature Tj in increments of the temperature step AT. The cooling period for rescaling the velocities. P... is defined by ... 

When using the heating and cooling features of IlyperChem ii should he remembered that ii is accomplished through rescalingof the velocities, so if the velocities are zero no tcmperaiurc can occur. This happens, for example, if you start with an exactly opti-mi/ed stni ctii re an d heat from a startm g lem perature Tj of/.ero.or use the restart option when velocities are all zero. 

Since we assume that all higher derivatives are essentially /.ero, dp/dq = con slim t. Therefore, it m ay be taken mi l of the in legral sign as follows ... 

Determinants have many useful and interesting properties. The determinant of a matrix is ero if any two of its rows or columns are identical. The sign of the determinant is reversed )y exchanging any pair of rows or any pair of columns. If all elements of a row (or column) ire multiplied by the same number, then the value of the determinant is multiplied by that lumber. The value of a determinant is unaffected if equal multiples of the values in any row or column) are added to another row (or column). 

The acetolyses of both ero-2-norbomyl brosylate and e do-2-norbomyl brosylate produce exclusively exo-2-norbomyl acetate. The exo-brosylate is more reactive than the endo isomer by a factor of 350. Furthermore, enantiomerically enriched exo-brosylate gave completely racemic ero-acetate, and the endo-brosylate gave acetate that was at least 93% racemic. 

Both acetolyses were considered to proceed by way of a rate-determining formation of a carbocation. The rate of ionization of the ewdo-brosylate was considered normal, because its reactivity was comparable to that of cyclohexyl brosylate. Elaborating on a suggestion made earlier concerning rearrangement of camphene Itydrochloride, Winstein proposed that ionization of the ero-brosylate was assisted by the C(l)—C(6) bonding electrons and led directly to the formation of a nonclassical ion as an intermediate. 

Acetoxy-4a,5a-ethyleneandrost-6-en-3-one-4 -ero-5 -exo-dicarboxylic acid dimethyl ester, 348... 

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