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Formal Synthesis of the Anti‐Angiogenic Polyketide (−)‐Borrelidin under Asymmetric Catalytic Control
Author(s) -
Madduri Ashoka V. R.,
Minnaard Adriaan J.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201001284
Subject(s) - enantioselective synthesis , conjugate , polyketide , formal synthesis , combinatorial chemistry , chemistry , stereochemistry , bromide , total synthesis , modular design , catalysis , computer science , organic chemistry , mathematics , programming language , mathematical analysis , biosynthesis , enzyme
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.