1,6-asymmetric induction in boron-mediated aldol reactions: application to a practical total synthesis of (+)-discodermolide.
By relying solely on substrate-based stereocontrol, a practical total synthesis of the microtubule-stabilizing anticancer agent (+)-discodermolide has been realized. This exploits a novel aldol bond construction with 1,6-stereoinduction from the boron enolate of (Z)-enone 3 in addition to aldehyde 2. The 1,3-diol 7 is employed as a common building block for the C(1)-C(5), C(9)-C(16), and C(17)-C(24) subunits. [reaction--see text]
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, U.K. ip100@cus.cam.ac.uk
Delgado
Oscar
O
Florence
Gordon J
GJ
Lyothier
Isabelle
I
Scott
Jeremy P
JP
Sereinig
Natascha
N
D000473:Alkanes; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D002219:Carbamates; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011161:Porifera; D011753:Pyrones
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; C071229:discodermolide; D001895:Boron