Oral Delivery of Propofol with Methoxymethylphosphonic Acid as the Delivery Vehicle.

Phosphonamidate 3a of methoxymethylphosphonic acid (MMPA) with propofol (1) and l-alanine ethyl ester was found to be an efficient scaffold for the oral delivery of compound 1. The synthesis and evaluation of MMPA based phosphonamidates of compound 1, HSK3486 (2), and other phenolic drugs revealed the general application of MMPA as the effective delivery vehicle for phenolic drugs. On the basis of plasma concentrations of compound 1 and SN38 (14), the oral bioavailability of compound 3a and 15 in beagle dogs was found to be 97.6% and 34.1%, respectively.

Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics.

A novel series of optically active 2,6-disubstituted alkylphenols with improved anesthetic profiles compared to widely used propofol were synthesized. The incorporation of the cyclopropyl group not only increased the steric effect but also introduced stereoselective effects over their anesthetic properties. Compounds 1, 2, and 6 were selected as potential candidates for further preclinical development including studies of their water-soluble prodrugs. Clinical studies of candidate compound 6 (Haisco HSK3486) as a general anesthetic are being performed in Australia and China.

The synthesis of pennogenin 3-O-ß-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranoside.

Pennogenin 3-O-ß-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranoside, a monodesmosidic saponin isolated from Paris polyphylla Smith var. yunnanensis with promised antitumor activities, was firstly synthesized from glucoside thiol via nine steps and with 27% overall yield.