252342-49-7Relevant articles and documents
Macrodiolide formation by the thioesterase of a modular polyketide synthase
Zhou, Yongjun,Prediger, Patrícia,Dias, Luiz Carlos,Murphy, Annabel C.,Leadlay, Peter F.
supporting information, p. 5232 - 5235 (2015/04/27)
Elaiophylin is an unusual C2-symmetric antibiotic macrodiolide produced on a bacterial modular polyketide synthase assembly line. To probe the mechanism and selectivity of diolide formation, we sought to reconstitute ring formation in vitro by using a non-natural substrate. Incubation of recombinant elaiophylin thioesterase/cyclase with a synthetic pentaketide analogue of the presumed monomeric polyketide precursor of elaiophylin, specifically its N-acetylcysteamine thioester, produced a novel 16-membered C2-symmetric macrodiolide. A linear dimeric thioester is an intermediate in ring formation, which indicates iterative use of the thioesterase active site in ligation and subsequent cyclization. Furthermore, the elaiophylin thioesterase acts on a mixture of pentaketide and tetraketide thioesters to give both the symmetric decaketide diolide and the novel asymmetric hybrid nonaketide diolide. Such thioesterases have potential as tools for the in vitro construction of novel diolides. Think again: The thioesterase/cyclase enzyme of the elaiophylin polyketide synthase catalyzes symmetric diolide formation in vitro from a synthetic pentaketide substrate by an iterative mechanism. Unexpectedly, a tetraketide that is not itself a substrate can be co-opted in the presence of the pentaketide to produce an asymmetric macrodiolide.
Total synthesis of pteridic acids A and B
Dias, Luiz C.,Salles Jr., Airton G.
scheme or table, p. 5584 - 5589 (2009/12/03)
(Chemical Equation Presented) The total synthesis of pteridic acids A and B is reported. The convergent asymmetric synthesis involved the use of a diastereoselective ethyl ketone aldol reaction followed by an efficient spiroketalization and provided pteri
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 1: Synthetic Strategy and Preparation of a Common Precursor
Mickel, Stuart J.,Sedelmeier, Gottfried H.,Niederer, Daniel,Daeffler, Robert,Osmani, Adnan,Schreiner, Klaus,Seeger-Weibel, Manuela,Berod, Brigitte,Schaer, Karl,Gamboni, Remo,Chen, Stephen,Chen, Weichun,Jagoe, Christopher T.,Kinder Jr., Frederick R.,Loo, Mauricio,Prasad, Kapa,Repic, Oljan,Shieh, Wen-Chung,Wang, Run-Ming,Waykole, Liladhar,Xu, David D.,Xue, Song
, p. 92 - 100 (2013/09/04)
The synthetic strategy for producing multigram quantities of (+)-discodermolide (1) using a hybridized Novartis-Smith-Paterson synthetic route via common precursor 3 is described. In the first part of this five-part series, we present a multikilogram preparation of α-methyl aldehyde 10 from Roche ester, its syn-aldol reaction with Evans boron enolate, removal of the chiral auxiliary, and the preparation of Weinreb amide 3 (Smith common precursor). The common precursor was produced without any chromatography.
