Molecular dynamics investigations into active site plasticity of Trypanosoma cruzi trans-sialidase, a protein implicated in Chagas disease, suggest that movement of the Trp(312) loop plays an important role in the enzyme's sialic acid transfer mechanism. The observed Trp(312) flexibility equates to a molecular shovel action, which leads to the expulsion of the donor aglycone leaving group from the catalytic site. These computational simulations provide detailed structural insights into sialyl transfer by the trans-sialidase and may aid the design of inhibitors effective against this neglected tropical disease.

The reaction of ring-closing metathesis-derived cyclic allylsiloxanes 3 with aldehydes in the presence of a Lewis acid gives 2,3,4-trisubstituted tetrahydrofurans related to the furanolignan family of natural products. The reactions proceed with complete 3,4-trans stereoselectivity, whereas the C-2 stereochemistry depends on both the aldehyde and Lewis acid used. When boron trifluoride etherate is used with aliphatic or electronically neutral aryl aldehydes, the reactions favor the production of the 2,3-cis isomer 8, whereas electron-rich aryl aldehydes lead to the 2,3-trans isomer 9 by Lewis acid-mediated isomerization of the kinetically favored cis isomer. The isomerization can be avoided by use of TMSOTf as a promoter, and hence, the stereochemistry can be tuned by appropriate choice of reagent. Cleavage of the pendant 3-ethenyl group installs the 3-hydroxymethyl group common to the furanolignans.

The scope of dimerization and isomerization reactions of alpha-lithiated terminal aziridines is detailed. Regio- and stereoselective deprotonation of simple terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide (LTMP) or lithium dicyclohexylamide (LiNCy2) generates trans-alpha-lithiated terminal aziridines. These latter species can then undergo dimerization or isomerization reactions depending on the nature of the N-protecting group. alpha-Lithiated terminal aziridines bearing N-alkoxycarbonyl (Boc) protection undergo N- to C-[1,2] migration to give N-H trans-aziridinylesters. In contrast, aziridines bearing N-organosulfonyl [tert-butylsulfonyl (Bus)] protection undergo rapid dimerization to give 2-ene-1,4-diamines or, if a pendant alkene is present, diastereoselective cyclopropanation to give 2-aminobicyclo[3.1.0]hexanes. All of these reactions were used as key steps in the preparation of synthetically and biologically important targets.