Michel Arbelot

New computer-based approach for seeking a key step in the synthesis of complex structures. Application to Taxane and Crinipellin Diterpenoid Frameworks.

Abstract We describe a new approach to map the precursors of complex target structures, involving a key transform, employing a new version of our SOS program which works both backward and forward. In this approach target and reactions are coded on a skeleton model. Results obtained for two diterpenoid frameworks (taxane and crinipellin) of current interest are discussed.

gasp: a computer program to generate automatically polycyclic structures

Abstract We present a new program to generate a virtual library of structures. gasp (Generation Automatique de Structures Polycycliques) answers to a question like: generate all structures with 3 rings of size 4, 6 and 8 for example. We present the results obtained for ‘isomers’ of several structures (steroid, taxane and triquinane skeletons). For steroid skeleton (4 rings of size 6, 6, 6 and 5) 988 structures were generated. Among them 48 are composed of fused rings. Comparison with the Beilstein database showed that among these 48 structures 21 are new.

SCORE: A program to explore the SCOpe of a given intramolecular REaction. How to find systematically the relevancy of a transform to various classes of structures. Application to the De Mayo reaction

Abstract We describe and publish the program SCORE (SCOre of a REaction). SCORE is a new computer program in the field of computer-aided organic synthesis. SCORE tries to answer the question: What kind of cyclic structures is it possible to obtain from a given reaction? Examples obtained for the De Mayo reaction are presented. The instruction manual and complete executable SCORE program for the PC are included.

QUANTITATIVE STUDY OF THE NUCLEOPHILICITY OF THE THIOCARBONYL GROUP IN HETEROCYCLIC COMPOUNDS

Abstract When the kinetic constants of reactions between alkyl iodides and a number of hetero-cyclic thiocarbonyl derivatives are measured in solvent acetone, the reactivity extends over three orders of magnitude. The increasing nucleophiliticy is found in the series: Bulkiness of the alkyl group in the alkylating agent has little influence when compared to the pyridine case. A correlation is found between the nucleophilic polarization energy calculated with HMO approximation and the measured constants.

Reactivity of Sulfur-Centered Nucleophiles Towards Dia- and Paramagnetic Reagents. The Frontier Orbitals Approach

Considering the large polarisability of sulfur, any nucleophiles centered on sulfur have often been classified as “soft” nucleophiles and their general reactivity has been rationalized along this line.

Computer analysis to produce univocal reactions sets: Possible application to the analysis of complex mixtures

Abstract We present CAPURS a program which, fed with a set of empirical formulae of compounds found in a reaction mixture, provides the complete set of all univocal balanced equations.

Computer‐aided organic synthesis. Extraction of informations from reaction databases

We present here our first attempt for transferring REACCS databases from mainframe computer to a microcomputer. This goal has been achieved by developing a very compact code for molecules. For example the average length of a molecule is 38 bytes for 16 atoms, this code includes coordinates for the drawing of structures and informations about charges, stereocenters and flags for bonds participating in the reactions. A new program named Holowin, which will use these databases, is under development.

Isoreferential planes of acidity, basicity, nucleophilicity, electrophilicity. A new graphical representation of double scales and its consequences in terms of selectivity and inversions of ranking in set of acids or bases, nucleophiles or electrophiles

Abstract An original graphical representation of relationships between acids and bases or between electrophiles and nucleophiles is proposed. It is based on the notion of an isoreferential plane of reactivity. An isoreferential plane of reactivity contains all the quantitative homologous measurements of a set of bases (nucleophiles) toward a given acid (electrophile). Symmetrically, the same representation applies to sets of acids (electrophiles) opposed to a given base (nucleophile). The relative spatial disposition of isoreferential planes associated with different acids (electrophiles) indicates immediately if inversions of ranking in reactivity of bases (nucleophiles) are expected to occur when one passes from one acid (electrophile) to another. A program (DBLSCALE on Disk 18) written in Basic and working on PC computers (IBM and IBM compatibles) allows the direct representation, on the screen, of sets of donors and acceptors, using the parameters derived from Dragos Double Scale approach.

Angular versus linear transition state in nucleophilic reactions of thioketones

The steric effect of o-methyl groups is much more pronounced for N-alkylation with Mel, Etl, and PriI or aza-aromatic compounds than for S-alkylation of heterocyclic thiones. This is explained by comparison of van der Waals interactions in the transition states of chosen homomorphic systems; an angular transition state is shown to conform with the measured kinetic constants.