Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non-UV-Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method.

Property tuning by fluorination is very effective for a number of purposes, and currently increasingly investigated for aliphatic compounds. An important application is lipophilicity (log P) modulation. However, the determination of log P is cumbersome for non-UV-active compounds.

A linear synthesis of gemcitabine.

Gemcitabine, 2'-deoxy-2',2'-difluorocytidine, is currently prescribed against a number of cancers. Here we report a linear synthesis of gemcitabine with a high-yielding direct conversion of 3,5-di-O-benzoyl-2-deoxy-2,2-difluororibose into the corresponding glycosyl urea as the key step, followed by conventional conversion to the cytosine base via the uracil derivative. The process proceeded with modest anomeric selectivity.

The synthesis of gemcitabine.

Gemcitabine is a fluorinated nucleoside currently administered against a number of cancers. It consists of a cytosine base and a 2-deoxy-2,2-difluororibose sugar. The synthetic challenges associated with the introduction of the fluorine atoms, as well as with nucleobase introduction of 2,2-difluorinated sugars, combined with the requirement to have an efficient process suitable for large scale synthesis, have spurred significant activity towards the synthesis of gemcitabine exploring a wide variety of synthetic approaches.