Crotylsilane reagents in the synthesis of complex polyketide natural products: total synthesis of (+)-discodermolide.
An efficient, highly convergent stereocontrolled synthesis of (+)-discodermolide has been achieved with 2.1% overall yield (27 steps longest linear sequence). The absolute stereochemistry of the C1-C6 (12), C7-C14 (13), and C15-C24 (11) subunits was introduced using asymmetric crotylation methodology. Key elements of the synthesis include the use of hydrozirconation-cross-coupling methodology for the construction of C13-C14 (Z)-olefin, acetate aldol reaction to construct the C6-C7 bond and install the C7 stereocenter with high levels of 1,5-anti stereoinduction, and the use of palladium-mediated sp(2)-sp(3) cross-coupling reaction to join the advanced fragments, which assembled the carbon framework of discodermolide.
Arefolov
Alexander
A
Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, 590 Commonwealth Avenue, Boston University, Boston, Massachusetts 02215, USA.
Panek
James S
JS
D000473:Alkanes / Q000138:chemical synthesis*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002219:Carbamates / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D011161:Porifera / Q000737:chemistry; D011753:Pyrones; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; D012821:Silanes; C071229:discodermolide