Collective Asymmetric Total Synthesis of Cylindricines

Abstract

Collective asymmetric total synthesis of marine tricyclic alkaloids, cylindricines A−H, and the proposed structures of cylindricines I and J was achieved in a concise manner from a single common spirocyclic pyrrolidine intermediate. A tandem chemoselective oxidation/intramolecular aza-Michael addition/epimerization was exploited to complete the tricyclic skeleton. This work provides a versatile synthetic entry to the cylindricine family of marine tricyclic alkaloids.

Gold-catalyzed cyclization and cycloaddition in natural product synthesis

“…The key intermediate was subsequently converted to (−)-lepadiformine A (240), and then cylindricines, including (+)-cylindricine A (241). 178 Isolated from the sponge Dysidea sp. endemic to the South China Sea, 179 (+)-dysiherbol A was originally assigned as 246, characterized by a hydroquinone sesquiterpene bearing a 6/6/5/6 tetracyclic core.…”

“…The key intermediate was subsequently converted to (−)-lepadiformine A ( 240 ), and then cylindricines, including (+)-cylindricine A ( 241 ). 178…”

Au-catalyzed stereodivergent synthesis of 2,5-disubstituted pyrrolidines: total synthesis of (+)-monomorine I and (+)-indolizidine 195B

“…4 The Au-catalyzed tandem reaction could also be performed in an intramolecular format to access a 1-azaspiro[4.5]decane derivative, which served as a common intermediate in total synthesis of lepadiformine A 4 and cylindricines A–J. 5…”

“…4 The Au-catalyzed tandem reaction could also be performed in an intramolecular format to access a 1-azaspiro [4.5]decane derivative, which served as a common intermediate in total synthesis of lepadiformine A 4 and cylindricines A-J. 5 Here we disclose a stereodivergent synthesis of 2,5-disubstituted pyrrolidine derivatives via a Au-catalyzed tandem intramolecular hydroamination/iminium formation/Et 3 SiH reduction of amino alkynes 6 (Scheme 1: I -II -III -2,5-cis-V/2,5-trans-V), and its application to asymmetric total synthesis of a diastereomeric pair of indolizidine alkaloid natural products, (+)-monomorine I and (+)-indolizidine 195B.…”