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An algorithm has been developed and implemented to generate for each chemical structure a unique and invariant linear name which includes double bond and asymmetric carbon isomerism. A logical proof is given for the one-to-one correspondence between name and structure. By inspection of the linear names of two structures, one can determine if the two structures are identical, nonisomeric, constitutionally isomeric, diastereomeric, or enantiomeric. The algorithm determines the true stereocenters and calculates a reduced set of chiral centers, SRC. It is proven that if there are any centers in SRC that the compound must be chiral; an achiral compound must have SRC = null. Extensions of the algorithm are outlined to allow uniquely naming conformational isomers. onunique representations of chemical structures are

Grignard reagents (aliphatic, aromatic, heteroaromatic, vinyl, or allylic) react with 1 equiv of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (pinacolborane, PinBH) at ambient temperature in tetrahydrofuran (THF) to afford the corresponding pinacolboronates. The initially formed dialkoxy alkylborohydride intermediate quickly eliminates hydridomagnesium bromide (HMgBr) and affords the product boronic ester in very good yield. Hydridomagnesium bromide (HMgBr) in turn disproportionates to a 1:1 mixture of magnesium hydride (MgH(2)) and magnesium bromide (MgBr(2)) on addition of pentane to the reaction mixture. DFT calculations (Gaussian09) at the B3LYP/6-31G(d) level of theory show that disproportionation of HMgBr to MgH(2) and MgBr(2) is viable in the coordinating ethereal solvents. This reaction also can be carried out under Barbier conditions, where the neat PinBH is added to the flask prior to the in situ formation of Grignard reagent from the corresponding organic halide and magnesium metal. Pinacolboronic ester synthesis under Barbier conditions does not give Wurtz coupling side products from reactive halides, such as benzylic and allylic halides. The reaction between PinBH and various Grignard reagents is an efficient, mild, and general method for the synthesis of pinacolboronates.

The application of computer graphics to input and output chemical structures is described. The graphics program which has been developed for use in computer-assisted synthetic analysis allows a high degree of interaction between man and computer. Details are given with regard to the performance of the graphics program, its organization, structure, and adaptation to a particular machine (Digital Equipment Corporation PDP-1).reviously we have discussed the general theory of P synthetic analysis as applied to complex molecules and a particularly simple yet powerful technique for the design of organic syntheses which has been termed the "logic-centered" approach. In its "pure" form this method starts from the synthetic objective or "target molecule" and is directed in a series of analytical stages to a set of possible synthetic starting points. The first step is the derivation of the set of precursor molecules which can reasonably be expected to be converted to the target by one synthetic reaction or a simple sequence of reactions. Each precursor molecule so generated is then considered to be a target and analyzed similarly, generating a "tree" of synthetic intermediates. Each precursor is in some way simpler than the target from which it was derived or leads in further analysis t o precursors which are simpler. The analysis terminates when precursors are elaborated which are considered to be relatively simple or readily available.The exceedingly large number of intermediates which would be involved in a comprehensive synthesis tree for a complicated molecule could only be generated by the expenditure of very large amounts of time and effort by a knowledgeable chemist. Some time ago we embarked upon the task of writing an experimental problem-solving computer program to assist a chemist in the more cumbersome aspects of synthetic analysis. The results of the first phase of this work and a general background of the computer-assisted synthetic analysis technique have recently been presented. The early program, designated OCSS (Organic Chemical Simulation of Synthesis), was designed to be used interactively in real time by the chemist. It made possible a wider and more rapid investigation of the synthetic tree and allowed an unbiased evaluation of the principles and systematics of the program in a way which led naturally to improvement and extension. The validity of the synthetic tree generated by the machine is a true reflection of the effectiveness of the logic-centered principles, since a computer cannot rely on "prior synthetic experience" or judgement. see also E.

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In this paper, we present a novel approach to shape-based molecular similarity searching. The method that we introduce is able to superimpose dissimilar molecules by using geometrically invariant molecular surface descriptors. The shape descriptors are calculated by least-squares fitting of a quadratic function to small sections of the molecular surface of a ligand. Invariant geometric properties of the approximated surface patch are then extracted from the fitted quadratic function. The extracted properties are used to quantify the shape and to obtain a canonical orientation for this section of surface. The superimposition algorithm uses these geometric invariants to recognize similar regions of surface shape existing on two molecules and to bring these regions (and consequently the molecules) into registration. Because these geometric descriptors are based upon local surface shape, the superimposing algorithm is insensitive to the connectivity and the relative sizes of the molecules being matched. The capabilities of our algorithm are demonstrated by superimposing dissimilar ligands known to inhibit the same enzyme system. In all cases examined the algorithm generates superpositions that are in agreement with crystallographic results. The algorithm is also applied to align the two different proteins on the basis of the shape of their active sites.

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