Synthesis of a chiral metabolite

ProSynth was approached by a potential client regarding the synthesis of a chiral metabolite that had been observed. The structure of the metabolite was not exactly known, but was inferred from the mass spectrum of the tiny amount that had been isolated.

ProSynth designed a plausible but lengthy multi-stage route of synthesis to the putative structure, and successfully produced 2 grams of racemic material which confirmed the structure of the metabolite. As with almost all projects we undertake, this service was offered on a “no win, no fee” basis – a demonstration of our commitment to deliver what has been ordered from us.

It was subsequently demonstrated that one enantiomer of the metabolite was therapeutically potent. We were asked to revisit and improve the synthesis on increasing scales, and were able to:

a) Achieve production of the desired chiral material at ee>99%
b) Redesign the route to avoid aggressive and explosive intermediates
c) Remove the requirement for chromatographic purification from most, and eventually all stages of the synthesis

Again, almost all aspects of the development were undertaken on a “no win, no fee” basis.

ProSynth then went on to produce six batches, each of 6 kilos of material, all with ee>99% and achiral HPLC purity>98% (more latterly >99%), in the course of one year. We are currently in the process of transferring the latter stages of the synthesis to a cGMP compliant partner for clinical trials.

Author: Dr Don A Gilbert