“Slim” Nucleosides and Nucleotides. I. Synthetic, Structural and Biophysical Investigations of Showdomycins

Abstract

A new, convenient, and short synthesis of 2'-deoxyshowdomycin, along with an improved procedure for the preparation of showdomycin, have been presented. A single-crystal X-ray structure of 1-benzyl-2'-deoxyshowdomycin (9) has been reported. Conformational studies using C.D. indicated that showdomycin exists predominantly in an anti conformation in aqueous solution. Molecular mechanics calculations using AMBER point to comparable binding energy of showdomycin-adenosine pair with the natural uridine-adenosine pair, but with a significant base-ribose conformational deviation from the natural array in the former. Implications of such a conformational deviation on tumor and viral replications have been discussed. Base-pairing studies employing high resolution NMR spectroscopy indicate that both showdomycin and epishowdomycin base-pair with adenosine-5'-monophosphate (AMP); however, while showdomycin also shows evidence of stacking, that was absent in epishowdomycin. Molecular modeling studies using QUANTA/CHARMm show that showdomycin is capable of forming a homopolymer duplex by base-pairing with poly(A), but with a considerably broader and deeper major groove. A heteropolymer duplex with a single insert of showdomycin exhibits tighter coiling at the point of insertion. A ten-picosecond dynamics simulation of the above heteroduplex revealed relaxation of the helix with disruption of H-bonding for two base pairs on either side of the insertion point, forming a large central cavity.

The Elusive Antiaromaticity of Maleimides and Maleic Anhydride: Enthalpies of Formation of N-Methylmaleimide, N-Methylsuccinimide, N-Methylphthalimide, and N-Benzoyl-N-methylbenzamide

“…The variously N -substituted maleimides and maleic anhydride are well established to be highly reactive dienophiles in the Diels−Alder reaction and addition across the carbon−carbon double bond are well-known to be highly facile. These phenomena have been interpreted as manifestations of antiaromaticity , arising from the formal presence of 4π ring electrons .…”