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Development of a Solid‐Phase Approach to the Natural Product Class of Ahp‐Containing Cyclodepsipeptides
Author(s) -
Stolze Sara C.,
Meltzer Michael,
Ehrmann Michael,
Kaiser Markus
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101757
Subject(s) - moiety , chemistry , natural product , aldehyde , combinatorial chemistry , solid phase synthesis , serine protease , retrosynthetic analysis , protease , stereochemistry , organic chemistry , total synthesis , biochemistry , enzyme , peptide , catalysis
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.