117582-92-0Relevant articles and documents
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
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 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.
