Behnke, Mark (NCATS)
David, Scott (Ricerca Biosciences, LLC)
Fry, Douglas (Ricerca Biosciences, LLC)
Hoekstra, William (Mycovia Pharmaceuticals Inc)
Yates, Christopher (Mycovia Pharmaceuticals Inc)
This technology relates to the discovery and development of a practical, scalable, and commercially viable method for the synthesis of the novel antifungal VT-1129. Cryptococcal meningitis (CM) is a fungal infection that is particularly prevalent in immune-compromised patients and can be treated by VT-1129. CM has a current estimated patient population of 1-1.25 million, predominately in sub-Saharan Africa and the developing world. Several deficiencies and difficulties preclude large-scale preparation and manufacturing with previous processes, which include high cost and potential safety issues. The method described in this invention enables the practical and economical synthesis of VT-1129 at a large scale.
The discovery described here can generally be used to prepare enantioenriched aminoalcohols that contain tertiary alcohol fragments, and their derivatives, including the novel antifungal VT-1129 used for treating cryptococcal meningitis.
This discovery has the following advantages over previous synthesis methods:
1) avoids using expensive chiral chromatography for separation and preparation of enantiomerically enriched aminoalcohols and derivatives
2) avoids using expensive chromatographic purification of intermediates
3) avoids using of cryogenic conditions in the process
4) avoids using unstable/explosive reagents
5) allows cost-efficient and scalable preparation applicable to commercial scale manufacturing