[reaction: see text] The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal 5 to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone 3 to aldehyde 4 in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter.
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http://dx.doi.org/10.1021/ol035797o | DOI Listing |
Org Lett
March 2023
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
A scalable total synthesis of leucascandrolide A macrolactone has been accomplished with a longest linear sequence of 17 steps from readily available feedstocks in 31.2% yield. The key steps in this synthesis are the enantioselective allylation reaction by chiral phosphoric acid (CPA)/CuBr cooperative catalysis and the diastereoselective catalytic crotylation in the presence of CPA with CuCl.
View Article and Find Full Text PDFChemistry
May 2018
Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.
An efficient synthesis of highly enantio-enriched tetrahydropyrans from readily available aldehydes, allylboronates, and syngas has been established by multiply relay catalysis of rhodium and chiral phosphoric acid. The cascade reaction integrates the asymmetric allylboration of aldehydes and alkene hydroformylation, providing a structurally diverse range of products with different workup procedures. The concise synthesis of key chiral building blocks to access herboxidiene and leucascandrolide A demonstrates the high synthetic utility of this method.
View Article and Find Full Text PDFOrg Chem Front
September 2016
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
An asymmetric synthesis of the 1 to 11 and 14 to 18 fragments of the macrocyclic portion of the antibiotic Leucascandrolide A was achieved in 21 total steps from an achiral dienoate. The key 4-hydroxy-2,5-pyran portion of the natural product was established by oxy-Michael cyclization of a 5,7,9,11-tetraol intermediate, which in turn was established by an iterative asymmetric-hydration of dienoates. Alternative strategies for establishing the polyol stereochemistry were explored.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2015
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467 (USA).
Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed.
View Article and Find Full Text PDFTetrahedron
July 2011
Department of Chemistry, Indiana University, Bloomington, IN 47405, United States.
Strategies for the stereocontrolled preparations of 2,6--and 2,6--substituted tetrahydropyrans have been devised. These studies have explored methodology for asymmetric induction in S' reactions using chiral 1,3,2-diazaborolidine controllers. Reactions with aldehydes at -78 °C yield nonracemic 1,5-diols for chemoselective internal backside displacements.
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