Ash Stevens LLC

Most cancer drugs are quite potent and represent a potential hazard to chemists conducting their synthesis. Chemical development teams must therefore integrate proper handing techniques for such compounds into their development plans. We describe the synthesis of the drug busulfan using barrier isolation technology. These systems are a general solution for the safe handling of many potent drugs, including those used to treat cancer. Drug Dev Res 71: 439–444, 2010. © 2010 Wiley‐Liss, Inc.

Clofarabine is a promising DNA polymerase inhibitor currently in clin. trials for a variety of liquid and solid tumor indications.The efforts for development of a new manufacturing process for clofarabine are presented.This new process allows for the reliable and efficient production of drug substance in high anomeric excess and high overall purity, without using chromatog.The high anomeric selectivity is achieved by reacting 2-chloroadenine with 1-bromo-2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-ribofuranose (4) and potassium tert-butoxide in a mixture of three solvents.Following crystallization, anomeric ratios exceeding 50 (β/α) are achieved.Deprotection and addnl. crystallization afford a clofarabine drug substance containing less than 0.1% of the α-anomer.

A simple and efficient synthesis of protected ribonolactone I, a key chiral precursor used in the syntheses of neplanocin A and cyclopentenylcytosine from readily available D-ribose is reported.