Amos B. Smith III :

The trispyrrolinone peptidomimetic

adopts a b -strand conformation in the solid state with the side-chain trajectories and carbonyl orientations nearly identical to those of the peptide-based molecule. Importantly, the unit cell reveals head-to-tail molecular stacking in conjunction with interstrand H-bonding, similar to the arrangement found in antiparallel b -sheets. Taken together, these results provide for the first time experimental evidence that the pyrrolinone NH proton displaced from the peptide backbone can form a hydrogen bond with the carbonyl of a neighboring strand. This result formed the basis for the HIV-1 protease inhibitor program at Penn.

Below is a Jmol representation of the crystal packing (hydrogen bonds are in red). To rotate the unit cell, move the cursor inside the java frame while holding down the (left) mouse button. To access a pop-up menu use the right button on a PC or do a command-click on a Mac while the cursor is inside the java frame! For example, do a "select > all" followed by "Atom > 100% vanderWaals" to display a space-filling model.


The compound shown below is a derivative of an intermediate in the synthesis of the marine natural product Spongistatin 1 which has extremely high antitumor activity. The derivative corresponds to the C(18-30) spiroketal of spongistatin 1. The spiroketal is distinguished by the fact that one of the pyran oxygens adopts an equatorial orientation relative to the other pyran ring. Most spiroketals have both pyran ring oxygens in an axial orientation to maximize the anomeric effect. Solution of the X-ray structure for this derivative unequivocally established that the stereochemistry for this fragment was correct for the synthesis of the natural product.

To interact with this molecule in a pop-up frame go here.