122547-72-2Relevant articles and documents
Total Synthesis of the Acetyl CoA Carboxylase Inhibitor Soraphen A: Asymmetric Tsuji Reduction Enables Successive Olefin Metathesis
Krische, Michael J.,Schempp, Tabitha T.
, p. 1016 - 1022 (2022/02/05)
The total synthesis of soraphen A, a myxobacterial metabolite and inhibitor of acetyl CoA carboxylase, was completed in 11 steps (longest linear sequence), less than half the steps previously required. Seven metal-catalyzed processes were deployed to unlock step-economy (comprising five asymmetric processes and four C-C bond formations). The present route does not utilize chiral auxiliaries, and four of five C-C bond formations exploit non-premetalated partners. To maximize convergency, an asymmetric Tsuji reduction was developed using a Pd-AntPhos catalyst that allows a metathesis-inactive allylic carbonate to serve as a masked terminal olefin, thereby enabling successive olefin metathesis events.
Total synthesis of soraphen A(1α)
Abel, Stephan,Faber, Dominik,Hueter, Ottmar,Giese, Bernd
, p. 188 - 197 (2007/10/03)
The convergent synthesis of macrolide soraphen A(1α) is described starting from glucose (western part) and mannose (eastern part). Mannose was converted into a 2-deoxyribohexopyranoside that could be methylated and reduced stereoselectively. Chain elongation at C-6 was carried out by stereoselective addition of a magnesium acctylide. The two fragments (western and eastern) were assembled by a Julia olefination followed by macrolactonization. The introduction of the methyl group at C-2 of norsoraphen occurred stereoselectively for thermodynamic reasons.
Antibiotics from Gliding Bacteria, LXV - Synthesis of Soraphen Analogues by Substitution of the Phenyl-C-17 Ring Segment of Soraphen A1&α
Schummer, Dietmar,Jahn, Thorsten,Hoefle, Gerhard
, p. 803 - 816 (2007/10/02)
The partial synthesis of 11 analogues of soraphen A1α (1) is described.Reductive lactone ring cleavage, transformation into (17R,S)-soraphenic acid 10 and cyclization provided unatural 17-epi-soraphen A1α (12).Removal of the phenyl-C-17 ring segment of 1 by cleavage of the lactone moiety and the C16/C-17 bond gave the aldehyde 16 as central intermediate.After homologation of 16, introduction of a new C-17 substituent R or H, and cyclization of the lactone ring, the soraphen analogues butyl-, thienyl-, and tolylsoraphen 2b, d, e and 22b, d, e and the desphenylsoraphen 2a were obtained.The ring-contracted soraphen analogues norsoraphen 29 and 30 and desphenylnorsoraphen 31 were synthesized by introduction of a phenyl group or reduction of the intermediate aldehyde 23 followed by cyclization to the lactone.The biological activity of the soraphen analogues against Candida albicans was determined.Compared to the natural product, all analogues exhibit reduced activity.The activity of the analogues strongly depends upon the nature of the substituent R, the configuration at the C-17, and the ring size. - Key Words: Antibiotics / Soraphen / Macrolide / Structure-activity relationship
