Substructure System

Attias R, Dubois J-E. Substructure systems concepts and classifications. J Chem Inf Comput Sci 1990 30 2-7. 

A recent study has compared the NCI-DCT system with the NIH-EPA Chemical Information System for the ability to perform substructure searches of large files of compounds (22). The Merck modification of the Walter Reed Army Institute of Research substructure search system was also compared. This report should be referred to for a detailed analysis of these major substructure systems. Another system, prepared with a smaller computer and a smaller set of chemicals, has been developed by Jurs and colleagues 23). All of these systems can be readily used in substructural analysis studies. It would appear that the exact coding system used in such studies is not critical, but no definitive comparisons of these systems for SAR utility have been performed. 

ROSDAL is used in the Beilstein-DIALOG system [17] as a data exchange format. The code can represent not only full structures and substructures but also some generic structures. 

The JME can also serve as a query input tool for structure databases by allowing creation of complex substructure queries (Figure 2-130), which are automatically translated into SMARTS [22]. With the help of simple HTML-format elements the creation of 3D structure queries is also possible, as were used in the 3D pharmacophore searches in the NCI database system [129]. Creation of reac-... 

Besides structure and substructure searches, Gmclin provides a special search strategy for coordiuation compouuds which is found in no other database the ligand search system, This superior search method gives access to coordination compounds from a completely different point of view it is possible to retrieve all coordination compounds with the same ligand environment, independently of the central atom or the empirical formula of the compound. 

The pre-processing concepts have been a more recent development of substructure searching systems. These approaches have become popular since the mid-1980s, when the cost of the storage devices (hard disks and CD-ROMs) decreased. 

The backtracking algorithm is the core part of every software system that performs substructure searching. There are other approaches which have been applied both as alternatives to the backtracking algorithm or (most usually) in combination with it. Section 6.3.3 describes the approaches used for the optimization of the... 

DayCart is a software cartridge which offers a range of operation on an Oracle database, such as complete structure, similarity, and substructure search. The software can be obtained from Daylight Chemical Information Systems, Inc. (Mission Viejo CA) URL www.daylight.com... 

CACTVS is a chemical information system which provides 2D and 3D complete structure, substructure, and similarity search on plain files of structures. The... 

The Rekker approach is still used with revised Z/ systems, e.g., in the software program Z/SYBYL [8]. Over recent decades various other substructure-based approaches have been developed that are mostly implemented and available as computer programs. 

The spectral signals are assigned to the HOSE codes that represent the corresponding carbon atom. This approach has been used to create algorithms that allow the automatic creation of "substructure-sub-spectrum databases that are now used in systems for predicting chemical structures directly from NMR. 

A useful empirical method for the prediction of chemical shifts and coupling constants relies on the information contained in databases of structures with the corresponding NMR data. Large databases with hundred-thousands of chemical shifts are commercially available and are linked to predictive systems, which basically rely on database searching [35], Protons are internally represented by their structural environments, usually their HOSE codes [9]. When a query structure is submitted, a search is performed to find the protons belonging to similar (overlapping) substructures. These are the protons with the same HOSE codes as the protons in the query molecule. The prediction of the chemical shift is calculated as the average chemical shift of the retrieved protons. 

A proton can be (numerically) represented by a series of topological and physicochemical descriptors, which account for the influence of the neighborhood on its chemical shift. Fast empirical procedures for the calculation of physicochemical descriptors are now easily accessible [45. Geometric descriptors were added in the case of some rigid substructures, as well as for rr-systems, to account for stereochemistry and 3D effects. 

To seat ch for available starting materials, similarity searches, substructure searches, and some classical retrieval methods such as full structure searches, name searches, empirical formula searches, etc., have been integrated into the system. All searches can be applied to a number of catalogs of available fine chemicals (c.g, Fluka 154]. In addition, compound libraries such as in-housc catalogs can easily be integrated. 

One of the hits found in the Chem Inform reaction database is shown in the window for reaction substructure searches in Figure 10.3-55. It fits the synthesis problem perfectly, since in the synthesis direction it forms the coumarin ring system directly, in one step. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Mendeleev s reluctance toward reduction was not widely shared. One of the codiscoverers of the periodic system, the German Lothar Meyer, accepted the possibility of primary matter and supported Prouf s hypothesis. He was also happy to draw curves through numerical data, including his famous plot of atomic volumes that showed such remarkable periodicity that it helped in the acceptance of the periodic system. Nonetheless, prior to Thomson s discovery of the electron, no accepted model of atomic substructure existed to explain the periodic system, and the matter was still very much in dispute. 

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