Synthesis of carbocyclic nucleosides

Synthetic aspects of diels-alder cycloadditions with heterodienophiles

γ-Amino acids have attracted considerable attention as biologically active compounds in the central nervous system (CNS) of mammals. Over the last few years, significant interest in the stereoselective synthesis and practical application of linear and cyclic chiral γ-amino acids in the synthesis and design of α,β- and β,γ-hybrid peptides with definite secondary structures and design of nanotubes has been reported, thus demonstrating the theoretical interest and the practical importance of γ-amino acids. An overview of synthetic approaches to linear and cyclic chiral γ-amino acids and derivatives is presented. Data on the practical applications of γ-amino acids are also discussed.

Stereoselective synthesis of γ-amino acids

A series of eight symmetrically substituted diketopiperazines (DKPs) derived from 1-amino-1-carboxycycloalkanes (n = 3−7; 3,3,5,5-tetramethylcyclohexane; 4,4-dimethylcyclohexane; 2-indan) were synthesized and their crystal structures determined. In the solid state, all eight compounds form two pairs of hydrogen bonds with two adjacent molecules to form a one-dimensional structure that we refer to as "tapes". These molecules represent a range of volumes and shapes that contain a common molecular fragment (DKP ring). We examined this series of compounds with three objectives in mind: (i) to establish the ability of the hydrogen-bonded "tape" motif to persist through these differences in volume and shape; (ii) to provide a series of structurally related compounds to use to test computational methods of predicting crystal structure from molecular structure; (iii) to search for qualitative correlations between molecular structure and crystal packing. All compounds form tapes and with one exception, all tapes pack with their long axes parallel. When viewed down their long axis, two types of tapes emerge: planar and nonplanar. The type of tape that forms reflects the conformation adapted by the DKP ringplanar or boat. Planar tapes form when the angle (α) between the two planes defined by the cis-amides in the DKP ring is 180°; nonplanar tapes form when α < 180°. Five of the eight compounds studied form planar tapes, the remaining three compounds form nonplanar tapes. Despite the variability in volume and shape represented by this series of molecules, the persistence of the tape motif in their crystalline solids suggests that the hydrogen-bonding interactions between DKPs dominate the packing arrangement of these molecules. Void space in the crystalline solid is minimized by parallel alignment of tapes that pack in a manner that permits the interdigitation of substituents on adjacent tapes.

Hydrogen-Bonded Tapes Based on Symmetrically Substituted Diketopiperazines: A Robust Structural Motif for the Engineering of Molecular Solids

The optical resolution or chiral separation of one specific enantiomer from others is in demand for the production of pharmaceuticals because many pharmaceuticals exist as stereoisomers, with each enantiomer having different biological activity. There is considerable demand for separation techniques appropriate for the large-scale resolution of chiral molecules. Chiral separation of racemic mixtures of pharmaceuticals through chiral or achiral polymeric membranes with or without a chiral selector represents a promising system for future commercial application. This article reviews several polymeric materials for the chiral separation of pharmaceuticals. Several chiral separation membranes were prepared from chiral polymers where enantioselectivity was generated from chiral carbons in the main chain. However, it is rather difficult to generate excellent chiral separation membranes from chiral polymers alone, because racemic penetrants mainly encounter the flexible side chains of the membrane polymers. Ther...

Polymeric membranes for chiral separation of pharmaceuticals and chemicals

Diels-alder cycloadditions of sulfonyl cyanides with cyclopentadiene - synthesis of "2-azabicyclo[2.2.1]hepta-2,5-dienes

Tosyl cyanide reacts under extremely mild conditions with 2,3-dimethyl-1,3-butadiene, isoprene and, under somewhat different conditions, with 1,3-butadiene. The products, 2-tosylpyridines and 3,6-dihydro-2-pyridones, are derived by dehydrogenation and hydrolysis, respectively, of the Diels-Alder cyclo-adducts formed in situ. Phenylmethanesulfonyl cyanide and 1-adamantane-sulfonyl cyanide give analogous results with 2,3-dimethylbutadiene.



At 175°C, tosyl cyanide and tetracyclone form 3,4,5,6-tetraphenyl-2-tosylpyridine. Phenylmethanesulfonyl cyanide and p-chlorobenzenesulfonyl cyanide react similarly.

Jc Jagt

Papers

Diels-alder cycloadditions of sulfonyl cyanides with cyclopentadiene - synthesis of "2-azabicyclo[2.2.1]hepta-2,5-dienes

Chemistry of sulfonyl cyanides .4. diels-alder cycloadditions of sulfonyl cyanides with dienes