Solid-phase synthesis of rigid acylpolyamines using temporary N-4,4'-dimethoxytrityl protection in the presence of trityl linkers.
An N-protection protocol employing the 4,4'-dimethoxytrityl (Dmt) group in combination with borane reduction of resin-bound polyamides was shown to be an efficient methodology that enables synthesis of novel analogues of natural acylpolyamine toxins. Thus, three philanthotoxins containing polyamine chains with piperidyl and cyclohexyl structural elements, which introduce conformational rigidity, increased lipophilicity, and altered proteolytic properties, were obtained in 39-44% overall yield.
Olsen
Christian A
CA
Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Witt
Matthias
M
Jaroszewski
Jerzy W
JW
Franzyk
Henrik
H
D001880:Boranes / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D011073:Polyamines / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014320:Triphenylmethyl Compounds / Q000737:chemistry*; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000737:chemistry*
D001880:Boranes; D011073:Polyamines; D014320:Triphenylmethyl Compounds; D014862:Wasp Venoms; C034092:delta-philanthotoxin