Bianca R. Sculimbrene

The desymmetrization of ten prochiral diols by phosphoryl transfer with a titanium-BINOLate complex is discussed. The phosphorylation of nine 1,3-propane diols is achieved in yields of 50–98%. Enantiomeric ratios as high as 92:8 are achieved with diols containing a quaternary C-2 center incorporating a protected amine. The chiral ligand, base, solvent, and stoichiometry are evaluated along with a nonlinear effect study to support an active catalyst species that is oligomeric in chiral ligand. The use of pyrophosphates as the phosphorylating agent in the desymmetrization facilitates a user-friendly method for enantioselective phosphorylation with desirable protecting groups (benzyl, o-nitrobenzyl) on the phosphate product.

We herein report two examples of one pot, simultaneous reactions, mediated by multiple, orthogonal catalysts with the same catalytic motif. First, BINOL-derived chiral phosphoric acids (CPA) and phosphothreonine (pThr)-embedded peptides were found to be matched for two different steps in double reductions of bisquinolines. Next, two -methylhistidine (Pmh)-containing peptides catalyzed enantio- and chemoselective acylations and phosphorylations of multiple substrates in one pot. The selectivity exhibited by common reactive moieties is adjusted solely by the appended chiral scaffold through outer-sphere interactions.

Lanthanide-binding tags (LBTs) are small, genetically encoded, versatile protein fusion partners that selectively bind lanthanide ions with high affinity. The LBT motif features a strategically positioned tryptophan residue that sensitizes Tb³⁺ luminescence upon excitation at 280 nm. Herein, we describe the preparation of new LBT peptides that incorporate unnatural amino acids in place of tryptophan, and which sensitize both Tb³⁺ and Eu³⁺ luminescence at lower energies. We also report the semisynthesis of proteins tagged with these new LBTs using native chemical ligation. This expands the scope of LBTs and will enable their wider use in luminescence applications.