1521267-03-7Relevant articles and documents
Total Synthesis of (-)-Lasonolide A
Trost, Barry M.,Stivala, Craig E.,Fandrick, Daniel R.,Hull, Kami L.,Huang, Audris,Poock, Caroline,Kalkofen, Rainer
, p. 11690 - 11701 (2016/10/06)
The lasonolides are novel polyketides that have displayed remarkable biological activity in vitro against a variety of cancer cell lines. Herein we describe our first-generation approach to the formal synthesis of lasonolide A. The key findings from these studies ultimately allowed us to go on and complete a total synthesis of lasonolide A. The convergent approach unites two highly complex fragments utilizing a Ru-catalyzed alkene-alkyne coupling. This type of coupling typically generates branched products; however, through a detailed investigation, we are now able to demonstrate that subtle structural changes to the substrates can alter the selectivity to favor the formation of the linear product. The synthesis of the fragments features a number of atom-economical transformations which are highlighted by the discovery of an engineered enzyme to perform a dynamic kinetic reduction of a β-ketoester to establish the absolute stereochemistry of the southern tetrahydropyran ring with high levels of enantioselectivity.
A concise synthesis of (-)-lasonolide A
Trost, Barry M.,Stivala, Craig E.,Hull, Kami L.,Huang, Audris,Fandrick, Daniel R.
supporting information, p. 88 - 91 (2014/01/23)
Lasonolide A is a novel polyketide displaying potent anticancer activity across a broad range of cancer cell lines. Here, an enantioselective convergent total synthesis of the (-)-lasonolide A in 16 longest linear and 34 total steps is described. This approach significantly reduces the step count compared to other known syntheses. The synthetic strategy utilizes alkyne-bearing substrates as core building blocks and is highlighted by stitching together two similarly complex halves via a key Ru-catalyzed alkene-alkyne coupling and macrolactionization.
