Structure Determination and Total Synthesis of (+)‐16‐Hydroxy‐16, 22‐dihydroapparicine. Issue 32 (20th June 2013)

• Record Type: Journal Article
• Authors: Hirose, Tomoyasu; Noguchi, Yoshihiko; Furuya, Yujiro; Ishiyama, Aki; Iwatsuki, Masato; Otoguro, Kazuhiko; Ōmura, Satoshi; Sunazuka, Toshiaki
• Is Part Of: Chemistry. Volume 19:Issue 32(2013)
• Page Start: 10741
• Page End: 10750
• Publication Date: 2013-06-20
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201300292
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Herein, we describe the first asymmetric total synthesis and determination of the relative and absolute stereochemistry of naturally occurring 16‐hydroxy‐16, 22‐dihydroapparicine. The key steps include 1) a novel phosphinimine‐mediated cascade reaction to construct the unique 1‐azabicyclo[4.2.2]decane core, including a pseudo‐aminal‐type moiety; 2) a highly stereospecific 1, 2‐addition of 2‐acylindole or a methylketone through a Felkin–Anh transition state for the construction of a tetrasubstituted carbon center; and 3) an intramolecular chirality‐transferring Michael reaction of the ketoester, with neighboring‐group participation, to introduce a chiral center at C15 in the target molecule. In addition, we evaluated the antimalarial activity of synthetic (+)‐(15<italic>S</italic>, 16<italic>R</italic>)‐16‐hydroxy‐16, 22‐dihydroapparicine and its intermediate against chloroquine‐resistant <italic>Plasmodium falciparum</italic> (K1 strain) parasites.</p> </abstract>