Conformational analysis of furanoid epsilon-sugar amino acid containing cyclic peptides by NMR spectroscopy, molecular dynamics simulation, and X-ray crystallography: evidence for a novel turn structure.

Sugar amino acids (SAAs) are useful building blocks for the design of peptidomimetics and peptide scaffolds. The three-dimensional structures of cyclic hybrid molecules containing the furanoid epsilon-SAA III and several amino acids were elucidated to study the preferred conformation of such an epsilon-SAA and its conformational influence on the backbone of cyclic peptides. NMR-based molecular dynamics simulations and empirical calculations of the cyclic tetramer 1, consisting of two copies of the SAA residue and two amino acids, revealed that it is conformationally restrained.

2'-chloro-2',3'-dideoxy-3'-fluoro-d-ribonucleosides: synthesis, stereospecificity, some chemical transformations, and conformational analysis.

The synthesis of methyl 5-O-benzoyl-2-chloro-2,3-dideoxy-3-fluoro-beta-d-ribofuranoside (5) and its use as a glycosylating agent for persilylated thymine, N(6)-benzoyladenine, and N(4)-benzoylcytosine are described (Scheme 1). The 2'-chloro-2',3'-dideoxy-3'-fluoro-d-ribonucleosides 10-12 synthesized were transformed to 2',3'-dideoxy-3'-fluoro-alpha- and -beta-d-erythro-pentofuranoside nucleosides of thymine (13a,b), adenine (14a,b), and cytidine (15a,b) by treatment with tributyltin hydride in the presence of alpha,alpha'-azobisisobutyronitrile (Scheme 2). Treatment of 2'-chloro-2',3'-dideoxy-3'-fluoro-d-ribonucleosides with 1 M MeONa/MeOH under reflux for 1-5 h afforded 2',3'-didehydro-2',3'-dideoxy-2'-chloro-d-pentofuranosyl nucleosides as the principal products (47-81%) of the reaction, along with recovered starting nucleoside (11-33%) (Scheme 3).

Conformational analysis of furanose rings with PSEUROT: parametrization for rings possessing the arabino, lyxo, ribo, and xylo stereochemistry and application to arabinofuranosides.

The solution conformation of a furanose ring can be assessed through PSEUROT analysis of three-bond (1)H-(1)H coupling constants ((3)J(HH)) of the ring hydrogens. For each coupling constant, PSEUROT requires two parameters, A and B, which are used to translate the H[bond]C[bond]C[bond]H dihedral angle predicted from the (3)J(HH) into an endocyclic torsion angle from which the identity of the conformers can be determined. In this paper, we have used density functional theory methods to generate a family of envelope conformers for methyl furanosides 1-8.