Enantioselective Total Synthesis of (+)‐Nordasycarpidone, (+)‐Dasycarpidone, and (+)‐Uleine

Abstract

The structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro‐1H‐1,5‐methanoazocino[4,3‐b]indole ring system 1. Various strategies have been developed to access this polycyclic structural motif. We report herein a one‐step conversion of appropriately functionalized 1,3,4‐trisubstituted cyclopent‐1‐ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3‐bridged piperidine ring through formation of one C−C and two C−N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis‐3,5‐diacetoxy‐1‐cyclopentene.

Aza-Achmatowicz rearrangement coupled with intermolecular aza-Friedel–Crafts enables total syntheses of uleine and aspidosperma alkaloids

“…98–100 Finally, the synthesis of (+)-3- epi -uleine ( 13 ) was achieved in 44% yield by following Zhu's procedure. 101…”

A simple and efficient method for constructing azocino[4,3-b]indole

“…1). [9][10][11][12] These structures are two important classes of compounds and have been widely found in biolo-gically active molecules and drug candidates. Moreover, diversely functionalized azocino [4,3b]indoline skeletons have also been versatile synthetics in bioactive molecules.…”

Two-Carbon Ring Expansion of Cyclobutanols to Cyclohexenones Enabled by Indole Radical Cation Intermediate: Development and Application to a Total Synthesis of Uleine

“…To further showcase the synthetic utility of our methodology, a total synthesis of (±)-uleine ( 5 ) was pursued (Scheme ). The C2 lithiation of N -MOM indole ( 12 ) followed by an addition to 3-ethyl cyclobutanone ( 13 ) afforded cyclobutanol 1ai , which, upon being submitted to our standard conditions, was converted to 2ai in 60% yield on a 4.0 mmol scale . A diastereoselective allylation of the latter followed by an N- MOM deprotection afforded 14 as a major diastereomer.…”