George T. Furst

The solution structure of (+)-spongistatin 1 in DMSO.

The solution structure of (+)-spongistatin 1 (1) has been determined via 1- and 2-D NMR techniques in conjunction with extensive in silico conformational analysis to comprise a mixture of 4 major rapidly interconverting conformational families.

MOLECULAR MODELING, SYNTHESIS, AND STRUCTURES OF N-METHYLATED 3,5-LINKED PYRROLIN-4-ONES TOWARD THE CREATION OF A PRIVILEGED NONPEPTIDE SCAFFOLD

The molecular modeling, synthesis, and elucidations of the solid state and solution structures of N-methylated 3,5-linked bispyrrolin-4-ones are described. Prior investigations established that the 3,5-linked pyrrolin-4-one based scaffold can be incorporated into mimics of beta-sheet/beta-strands and into potent, orally bioavailable inhibitors of the HIV-1 protease. To extend the utility of this scaffold beyond that of the initially designed mimics of beta-sheet/beta-strands, we have now explored the structure of N-methylated pyrrolinones. Molecular modeling indicated that N-methylated bispyrrolinones could adopt three low-energy backbone conformations (ca. 165 degrees, 289 degrees, and 320 degrees). Upon their successful synthesis, structural elucidation both in the solid state and in solution revealed the existence of two of the three predicted backbone conformers (ca. 165 degrees and 289 degrees). Two structures were particularly noteworthy and completely unexpected. Mono-N-methyl bispyrrolinone (+)-1 self assembled in the solid state to form a novel helix, while the acetylene-linked dimer of (+)-1, designed to potentiate the observed helical array, instead associated via an intermolecular hydrogen bond in parallel columns. These serendipitous observations led us to speculate that the pyrrolinone moiety may in fact represent a privileged nonpeptide scaffold, able to mimic not only the extended beta-sheet/beta-strand conformation as initially targeted, but also diverse conformations including those analogous to beta-turns and helices. These seemingly unlimited conformations greatly expand the scope of this scaffold for the development of low-molecular weight ligands for biologically important macromolecules.

C71H2 cyclopropanes and annulenes: synthesis and characterization

Addition of diazomethane to a toluene solution of C70 affords a mixture of isomeric pyrazolines, which, upon photolysis, furnish two isomeric C71H2 cyclopropanes; thermolysis of the mixture produces two isomeric annulenes.

Structures of breynins A and B, architecturally complex, hypocholesterolemic spiroketal glycosides. A revised formulation of breynin B

Abstract The complete structures of breynins A and B ( 1 and 2 ), orally active hypocholesterolemic glycosides, have been established via NMR analysis and chemical correlation. Breynin B ( 2 ) proved to be a sulfoxide derivative of 1 , not the isomeric hemithioacetal 3 as proposed previously.

Preparation of NG-monoethyl-l-arginine

NG-Monoethyl-L-arginine, a putative in vivo product after administration of the potent hepatocarcinogen L-ethionine to rats, has been chemically synthesized by coupling N-ethyl, S- methylthiopseudouronium iodide with alpha-amino-blocked L-ornithine. The structure of the compound as NG-monoethyl-L-arginine was confirmed by 13C NMR. Its elution time on an automatic amino acid analyzer, Rf values using thin-layer chromatography, and isoelectric point have been compared with those of NG-monomethyl-L-arginine.