The total synthesis of (-)-callystatin A.
Callystatin A is a prominent member of a class of natural products which display promising growth inhibition of cancer cells in their biological profile. The challenging structure and the interesting biological activity of (-)-callystatin A fueled our interest in the synthesis of this marine natural product. We achieved the total synthesis using a highly convergent approach joining four subunits together with a Wittig olefination, a selective Heck reaction and an aldol reaction as the pivotal steps. The aldol reaction as one of the final transformations during the synthesis opens fast access to a variety of structural analogues and circumvents tedious protecting group manipulations. Here we report an improved synthesis utilizing a modified vinyl iodide which shortens the synthesis by two steps. Additionally, first biological results will be reported.
Kalesse
Markus
M
Institut für Organische Chemie der Universität Hannover Schneiderberg 1B, 30167 Hannover, Germany. Kalesse@chemie.fu-berlin.de
Chary
Khandavalli P
KP
Quitschalle
Monika
M
Burzlaff
Arne
A
Kasper
Cornelia
C
Scheper
Thomas
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003603:Cytotoxins; D005231:Fatty Acids, Unsaturated; C421091:callystatin A