Development of a Solid-Phase Approach to the Natural Product Class of Ahp-Containing Cyclodepsipeptides

In: European journal of organic chemistry : EurJOC, (2012) ; Nr. 8, S. 1616–1625
Zeitschriftenaufsatz / Fach: Biologie
The 3-amino-6-hydroxy-2-piperidone (Ahp) containing cyclodepsipeptides are an interesting class of natural products that inhibit S1 (trypsin and chymotrypsin-like) serine protease in a reversible, noncovalent manner, turning them into potential chemical tools for protease research. Their systematic use in chemical biology is however hampered by their tedious solution-phase chemical synthesis. To overcome this limitation, we report a solid-phase approach to Ahp cyclodepsipeptides that is based on the use of a maskedglutamic aldehyde moiety as a general Ahp precursor molecule. As a proof-of-concept, we therefore recently reported the solid-phase synthesis of Symplocamide A. Here, we want to give a full account on the development and application of the masked glutamic aldehyde moiety as well as the optimization of the solid-phase synthesis, which allowed the successful synthesis of the natural product Symplocamide A.