Design, total synthesis, and evaluation of C13-C14 cyclopropane analogues of (+)-discodermolide.
[structure: see text] The design, total synthesis, and biological evaluation of two C13-C14-cyclopropyl analogues [(+)-1 and (+)-2] of (+)-discodermolide have been achieved. Key features of the syntheses include highly stereoselective, hydroxyl-directed cyclopropanations of vinyl iodides and higher order cuprate-mediated cross-coupling reactions between cyclopropyl iodides and alkyl iodides. Biological evaluation revealed that neither orientation of the cyclopropyl methylene completely substitutes for the C14 methyl found in (+)-discodermolide (3).
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Xian
Ming
M
Liu
Fenghua
F
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D003521:Cyclopropanes; D007783:Lactones; D011753:Pyrones; C030797:cyclopropane; C071229:discodermolide