261968-07-4Relevant articles and documents
Synthesis of (Z)-Trisubstituted olefins by decarboxylative Grob-Type fragmentations: Epothilone D, discodermolide, and peloruside A
Prantz, Kathrin,Mulzer, Johann
experimental part, p. 485 - 506 (2010/06/14)
Methyl-branched (Z)-trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxideinduced Grob-type fragmentation as an easy access to trisubstituted olefins. In our case, β-mesyloxy δ-lactones with three stereogenic centers were chosen whose fragmentation underlies a high stereoelectronic control. Major challenges in the syntheses were the instailation of quaternary stereocenters, achieved by enzymatic desymmetrization of meso-diesters and by aluminiumpromoted stereoselective rearrangement of chiral epoxides, respectively. Different aldol strategies were developed for the formation of the fragmentation precursors. Additionally a short survey about nucleophilic additions to aldehydes with quaternary α-centers is presented.
A practical synthesis of (+)-discodermolide and analogues: Fragment union by complex aldol reactions
Paterson,Florence,Gerlach,Scott,Sereinig
, p. 9535 - 9544 (2007/10/03)
A practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall yield (23 steps longest linear sequence). The absolute stereochemistry of the C1-C6 (7), C9-C16 (8), and Csub
