117582-92-0Relevant academic research and scientific papers
Total synthesis of iejimalide B. An application of the Shiina macrolactonization
Schweitzer, Dirk,Kane, John J.,Strand, Daniel,McHenry, Peter,Tenniswood, Martin,Helquist, Paul
, p. 4619 - 4622 (2007)
(Chemical Equation Presented) The potent anticancer compound iejimalide B (1) was prepared by a total synthesis through a strategy that features Julia olefinations, Wittig olefinations, a Carreira enantioselective alkynylation, a Heck reaction, a Marshall
Total synthesis of Iejimalide B
Chen, Qingshou,Schweitzer, Dirk,Kane, John,Davisson, V. Jo,Helquist, Paul
, p. 5157 - 5169 (2011/08/09)
Iejimalide B, a structurally unique 24-membered polyene macrolide having a previously underutilized mode of anticancer activity, was synthesized according to a strategy employing Julia-Kocienski olefinations, a palladium-catalyzed Heck reaction, a palladium-catalyzed Marshall propargylation, a Keck-type esterification, and a palladium-catalyzed macrolide-forming, intramolecular Stille coupling of a highly complex cyclization substrate. The overall synthesis is efficient (19.5% overall yield for 15 linear steps) and allows for more practical scaled-up synthesis than previously reported strategies that differed in the order of assembly of key subunits and in the method of macrocyclization. The present synthesis paves the way for efficient preparation of analogues for drug development efforts.
Gram-scale synthesis of iejimalide B
Gagnepain, Julien,Moulin, Emilie,Fuerstner, Alois
, p. 6964 - 6972 (2011/07/30)
IejimalideB (2) is the most promising member of a small family of marine polyene macrolides endowed with remarkably selective activity against human cancer cell lines. As this product, however, is hardly available from the natural sources, a detailed evaluation requires the development of an efficient and practical synthetic approach. This challenge has now been met by adapting the first total synthesis of 2 previously reported by our group to the needs of high material throughput. Redesigning the access routes to the five required building blocks in combination with a careful optimization of the fragment coupling processes provided gram amounts of this valuable compound in a sequence of no more than 16 linear steps with an overall yield of about 7 %. Key elements of the successful strategy include: i) three hydrostannylation processes of elaborate terminal alkynes with "lower order" stannyl cuprates, ii) a Brown allylation, a Noyori transfer hydrogenation, and a Marshall propargylation to set the chiral centers at C9, C17, C22 and C23, and iii) a modified Takai-Utimoto olefination for the preparation of the very labile skipped 1,4-diene flanking the ester group. The assembly process benefited from a particularly mild protocol for the Stille cross-coupling previously developed in this laboratory, which clearly outperformed the alternative Suzuki reaction in terms of yield and scalability. The 24-membered macrocyclic frame was forged by a remarkably selective ring-closing metathesis reaction (RCM), in which two out of the ten double bonds present in the cyclization precursor were selectively activated with the aid of a second-generation Grubbs catalyst. Copyright
Total synthesis of iejimalide A-D and assessment of the remarkable actin-depolymerizing capacity of these polyene macrolides
Fuerstner, Alois,Nevado, Cristina,Waser, Mario,Tremblay, Martin,Chevrier, Carine,Teply, Filip,Aissa, Christophe,Moulin, Emilie,Mueller, Oliver
, p. 9150 - 9161 (2008/02/10)
A concise and convergent total synthesis of the highly cytotoxic marine natural products iejimalide A-D (1-4) is reported, which relies on an effective ring-closing metathesis (RCM) reaction of a cyclization precursor containing no less than 10 double bon
Total synthesis of iejimalide B
Fuerstner, Alois,Nevado, Cristina,Tremblay, Martin,Chevrier, Carine,Teply, Filip,Aissa, Christophe,Waser, Mario
, p. 5837 - 5842 (2007/10/03)
(Chemical Equation Presented) Metathesis to the rescue: Although counterintuitive at first sight, application of ring-closing metathesis (RCM) to a cyclization precursor containing 10 double bonds has led to the selective and high-yielding formation of the macrocyclic core of iejimalide B, a potent cytotoxic agent of marine origin. In contrast, a macrolactonization approach failed to afford this intricate target.
