Design, synthesis, and evaluation of carbamate-substituted analogues of (+)-discodermolide.
[Structure: see text] The design, syntheses, and biological evaluation of 22 totally synthetic analogues of the potent microtubule-stabilizing agent (+)-discodermolide (1) have been achieved. Structure-activity relationships of the C(19) carbamate were defined, exploiting two synthetically simplified scaffolds, as well as the parent (+)-discodermolide framework.
Smith
Amos B
AB
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Freeze
B Scott
BS
Lamarche
Matthew J
MJ
Hirose
Tomoyasu
T
Brouard
Ignacio
I
Rucker
Paul V
PV
Xian
Ming
M
Sundermann
Kurt F
KF
Shaw
Simon J
SJ
Burlingame
Mark A
MA
Horwitz
Susan Band
SB
Myles
David C
DC
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; C071229:discodermolide