Skeletal and Appendage Diversity as Design Elements in the Synthesis of a Discovery Library of Nonaromatic Polycyclic 5-Iminooxazolidin-2-ones, Hydantoins, and Acylureas.

Amino acid-derived cross-conjugated trienes were used as a starting point for the synthesis of a discovery library of over 200 polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas. The main feature of this library synthesis is a triple branching strategy which provides efficient access to five skeletally diverse scaffolds. In addition, four sets of building blocks were applied in both a front end and a back end diversification strategy. Multiple fused rings were obtained by cyclization of diamides with phosgene and stereoselective Diels-Alder reactions with maleimides. The 5-iminooxazolidin-2-one scaffold was rearranged into the isomeric hydantoin scaffold through a sequence of ring opening and ring closing reactions.

Tandem cationic aza-cope rearrangement-Mannich cyclization approach to the core structure of FR901483 via a Bridgehead iminium ion.

[reaction in text] An approach to the potent immunosuppressant FR901483 is described. This route utilizes a tandem cationic aza-Cope rearrangement-Mannich cyclization to generate the core structure of this compound. In addition, this is the first demonstration of this tandem reaction passing through a bridgehead iminium ion.

Polymorphism in myristoylpalmitoylphosphatidylcholine.

This study focuses on the mixed-chain lipid myristoylpalmitoylphosphatidylcholine (MPPC) near full hydration. The lipid, synthesized according to the procedure of (Mason et al., 1981a, has a low degree of acyl chain migration. When MPPC is temperature-jumped (T-jumped) from the L alpha phase (T = 38 degrees C) to T = 20 degrees C or below, a subgel phase forms; this formation takes less than 1 h at a temperature below T = 12 degrees C. The subgel remains stable up to T = 29 degrees C. When MPPC is T-jumped from the L alpha phase to T = 24 degrees C or above, a ripple phase forms with coexisting ripple wavelengths of 240 A and 130 A. In contrast, when MPPC is melted from the subgel phase, the ripple phase is characterized by bilayers having a single ripple wavelength of 130 A. In agreement with earlier studies (Stumpel et al., 1983; Serrallach et al., 1984. Structure and thermotropic properties of mixed-chain phosphatidylcholine bilayer membranes. Biochemistry 23:713-720.), no stable gel phase was observed. Instead, an ill-defined low-angle X-ray pattern is initially observed, which gradually transforms into the subgel phase below 20 degrees C, or into the ripple phase above 24 degrees C. In the wide-angle X-ray diffraction, a single peak is observed, similar to the ripple phase wide-angle pattern, that either persists above 24 degrees C or transforms into a multi-peaked subgel wide-angle pattern below 20 degrees C. The absence of a gel phase can be understood phenomenologically as the relative dominance of the subgel phase in mixed-chain PCs compared to same-chain PCs. The subgel structure and molecular interactions responsible for this comparative behavior are interesting open issues.