Selective Lewis acid catalyzed assembly of phosphonomethyl ethers: three-step synthesis of tenofovir.

Described herein is a novel Lewis acid catalyzed rearrangement-coupling of oxygen heterocycles and bis(diethylamino)chlorophosphine that provides direct formation of the phosphonomethyl ether functionality found in several important antiretroviral agents. A wide range of dioxolanes and 1,3-dioxanes may be employed, furnishing the desired products in good yield. The utility of this method is demonstrated in a novel synthesis of tenofovir, an antiretroviral drug used in the treatment of HIV/AIDS and hepatitis B.

A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger mediated ring-closure.

Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing α-, β- or γ-amino acid residues is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and tripeptides--recognized as difficult targets--were obtained in moderate to good yields according to a straightforward sequence. Empirical force-field calculations were undertaken to determine their conformational behaviors and showed high levels of similarity with X-ray results.

Long-range intramolecular S → N acyl migration: a study of the formation of native peptide analogues via 13-, 15-, and 16-membered cyclic transition states.

The intramolecular long-range S → N acyl migration via 13-, 15-, and 16-membered cyclic transition states to form native tetra- and pentapeptide analogues was studied on S-acylcysteine peptides containing β- or γ-amino acids. The pH-dependency study of the acyl migration via a 15-membered cyclic transition state indicated that the reaction is favored at a pH range from 7.0 to 7.