Formal synthesis of the anti-angiogenic polyketide (-)-borrelidin under asymmetric catalytic control.
Borrelidin (1) is a polyketide that possesses extremely potent anti-angiogenesis activity. This paper describes its formal total synthesis by the most efficient route to date. This modular approach takes optimal benefit of asymmetric catalysis and permits the synthesis of analogues; in addition, the high yields and selectivities obtained eliminate the need for separation of stereoisomers. The upper half of borrelidin has been accessed by iterative copper-catalysed asymmetric conjugate addition of methylmagnesium bromide, whereas synthesis of the lower half of the molecule was achieved by relying on asymmetric hydrogenation and cross-methathesis as key steps.
Madduri
Ashoka V R
AV
Department of Bio Organic Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Minnaard
Adriaan J
AJ
D002384:Catalysis; D003300:Copper / Q000737:chemistry; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D006865:Hydrogenation; D061065:Polyketides / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D005233:Fatty Alcohols; D061065:Polyketides; C005066:borrelidin; D003300:Copper