M. Diggelmann et al., Preparative LC/MS technology: A key component of the existing high speed synthesis platform at Syngenta, CHIMIA, 55(1), 2001, pp. 23-25
Sizable investments in laboratory automation and state-of-the-art purificat
ion equipment were made at Syngenta Crop Protection with the objective to i
ncrease synthesis capacity and effectively support typical lead optimizatio
n activities. The successful implementation of a high-speed-synthesis platf
orm consisted of the modular assembly of various commercially available liq
uid-handling workstations in combination with inhouse developed parallel sy
nthesis reaction manifolds. Preparative LC/MS technology was identified as
a key success factor for optimizing overall throughput by addressing existi
ng bottlenecks in parallel synthesis such as the fast and unattended isolat
ion of compounds. Automated data analysis is crucial for high-throughput qu
ality control and to allow all compounds of interprets to be sorted rapidly
, i.e. those having defined structures and passing predefined purity criter
ia. The integrated application of the tools as described is intended to sup
port chemists in their task to derive reliable structure-activity relations
hips more quickly and hopefully to shorten the time needed to identify inno
vative drug candidates.