252342-44-2Relevant 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.
Evolution of a gram-scale synthesis of (+)-discodermolide
Smith III, Amos B.,Beauchamp, Thomas J.,LaMarche, Matthew J.,Kaufman, Michael D.,Qiu, Yuping,Arimoto, Hirokazu,Jones, David R.,Kobayashi, Kaoru
, p. 8654 - 8664 (2007/10/03)
An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σr-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphonium salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.
