Larisa Golender

New supramolecular host systems. 2. 1,3,5,7-tetraoxadecalin, 1,2-dimethoxyethane and the Gauche effect reappraised. Theory vs. experiment.

Abstract The three 1,3,5,7-tetraoxadecalin diastereomers (1, 2 & 3), core moieties of new host and macromolecular systems, were calculated “

New supramolecular host systems. 41. novel diacetal podands, diazacrowns and cryptands

Abstract New and important key podands bearing the cis -1,3,5,7-tetraoxadecalin (TOD) core are reported, viz., 2,6-di(hydroxymethyl)- ( 2 ) and 2,6-di(aminomethyl)- cis -1,3,5,7-TOD ( 6 ), which lead to the first diazacrown-TOD compounds ( 9a ) and ( 9b ) and a corresponding cryptand ( 11 ) in the series. 9a&b exhibit very good alkali and earth-alkali ion inclusion ability with selectivity for K + and Ba +2 . Molecular dynamics (Insight/Discover/AMBER) on the crowns and cryptand were performed, including reparametrized MM3-GE calculations. A convincing case for the TOD based hosts was thus established.

New supramolecular host systems. 1. A structural and conformational study of the 1,3,5,7-tetraoxadecalin core system

Abstract This is the first in a series of studies of new host systems based on the 1,3,5,7-tetraoxadecalin (TOD) core moiety. The parent molecule ( 2 ) an

New supramolecular host systems. 5. Diacetals and macro-m-cyclophanes of aldaric esters: Synthesis, stereochemistry and conformational analysis☆

Abstract A general scheme of carbohydrate diacetal systems (Scheme 2) of the 1,3,5,7-tetraoxadecalin (TOD) type is presented. A sequence of reactions starting with dimethyl D-glucarate (4) (Scheme 3) lead to 2,6-diaryl-4,8-di (methoxycarbonyl)-cis-TOD podands (5 and 6) and to the novel dicarbamate macrocycles (8a,b), which constitute the first m-cyclophanes in the carbohydrate (d-gluco) series. The D-gluco - L-ido interconversion by equilibration of the methoxycarbonyl groups in 5, 6 and 9, was examined in the light of a conformational analysis of the methoxycarbonyl group and its anomeric effect in heterocyclic systems, using molecular mechanics techniques (MM3-GE, i.e., MM3 reparametrized for treatment of the gauche effect) and comparing with experimental data.

Relative stabilities and conformational ring inversion potentials in heterocyclic decalin systems and stereoelectronic implications

Abstract The energy differences between stereoisomers and the ring inversion potential surfaces of decalin ( 1 ) and various oxadecalins ( 2, 3 ), dioxadecalins ( 4–7 ), trioxadecalins ( 8, 9 ) and tetraoxadecalins ( 10, 11 ) were interrogated following the generally accepted scheme of a stepwise conformational six-ring inversion process and using molecular mechanics techniques (MM3 and MM3-GE, i.e. MM3 reparametrized for treatment of the “gauche effect”). The results were compared with some available experimental data and were also used to probe the validity of a recently elaborated protocol for ring-fragment analysis of oxygen-containing bicyclic systems in terms of their interannular fragment components: CCCC, CCCO, CCOC, COCOC and OCCO, the latter two with their corresponding stereoelectronic effects, namely, the “anomeric effect” and the “gauche effect”, respectively.

CONFORMER CLUSTERING ALGORITHM AND ITS APPLICATION FOR CROWN-TYPE MACROCYCLES

Abstract An efficient conformer clustering algorithm designed for treating molecular modeling problems of flexible molecules associated with a large variety of conformers is described. It incorporates a fast algorithm for the generation of chemical graph automorphisms allowing to easily discard equivalent conformers for symmetrical structures. The cluster is defined as a set of conformers deviating from the “central conformer” less than the allowed threshold. The deviation is calculated as a maximum distance between the matched atoms. Matched atoms can include all heavy atoms that can be superimposed according to graph automorphism mappings or a special subset of atoms indicated by the user. Using the “central conformer” as a meaningful representative of a cluster significantly reduces molecular modeling efforts without losing the features of the system. Application of the algorithm to the ion recognition study of the newly synthesized macrocyclic host is presented.

Small Cyclic Peptide Sar Study Using Apex-3D System: Somatostatin Receptor Type 2 (SSTR2) Specific Pharmacophores

Somatostatin (SST), Gly-Ala-Cys-Lys-Asn-Phe6-Phe7-Trp8-Lys9-Thr10-Phe11-Thr-Ser-Cys, is a pleiotropic regulatory hormone whose functions are mediated by a family of 5 G-protein coupled receptors (SSTR1–5). SST binds non-selectively to all five subtypes, and is unstable under physiological conditions. Numerous small, stable synthetic SST analogs that display varying degree of selectivity have been identified1. Detailed knowledge of the 3D-structure of the receptor recognition sites (pharmacophores) is necessary for rational design of new SST based drugs.