685895-62-9Relevant articles and documents
Stereodivergent, Chemoenzymatic Synthesis of Azaphilone Natural Products
Pyser, Joshua B.,Baker Dockrey, Summer A.,Benítez, Attabey Rodríguez,Joyce, Leo A.,Wiscons, Ren A.,Smith, Janet L.,Narayan, Alison R. H.
supporting information, p. 18551 - 18559 (2019/11/14)
Selective access to a targeted isomer is often critical in the synthesis of biologically active molecules. Whereas small-molecule reagents and catalysts often act with anticipated site- and stereoselectivity, this predictability does not extend to enzymes. Further, the lack of access to catalysts that provide complementary selectivity creates a challenge in the application of biocatalysis in synthesis. Here, we report an approach for accessing biocatalysts with complementary selectivity that is orthogonal to protein engineering. Through the use of a sequence similarity network (SSN), a number of sequences were selected, and the corresponding biocatalysts were evaluated for reactivity and selectivity. With a number of biocatalysts identified that operate with complementary site- and stereoselectivity, these catalysts were employed in the stereodivergent, chemoenzymatic synthesis of azaphilone natural products. Specifically, the first syntheses of trichoflectin, deflectin-1a, and lunatoic acid A were achieved. In addition, chemoenzymatic syntheses of these azaphilones supplied enantioenriched material for reassignment of the absolute configuration of trichoflectin and deflectin-1a based on optical rotation, CD spectra, and X-ray crystallography.
Synthesis of azaphilones and related molecules by employing cycloisomerization of o-alkynylbenzaldehydes
Zhu, Jianglong,Germain, Andrew R.,Porco Jr., John A.
, p. 1239 - 1243 (2007/10/03)
Right to the core: Gold(III)-catalyzed cycloisomerization of o-alkynylbenzaldehydes to 2-benzopyrylium salts and subsequent in situ oxidation have been employed to prepare the core structure of azaphilone natural products, such as the sphingosine kinase inhibitor S-15183 (see scheme, DCE = 1,2-dichloroethane, TFA = trifluoroacetic acid)), and several unnatural azaphilones.
