Synthesis of a Model Tetracyclic Core Structure of Calyciphylline B-Type Alkaloids

Abstract

Herein, we report the enantioselective synthesis of a functionalized aza-octahydropentalene and its elaboration to a model tetracyclic core structure of calyciphylline B-type alkaloids.

Strategies toward the Total Synthesis of Calyciphylline B-type Alkaloids: A Computational Perspective Aided by DFT Analysis

“…An initial foray into the construction of a tetracyclic core structure using an iminium ion/enamine ring closure approach in a model compound led to a tetrasubstituted tetracyclic intermediate with the incorrect strereochemistry at C7 for deoxycalyciphyllin B. 12 It also became clear early on that this strategy would not lead to the desired stereochemistry at C7 when the appropriate bicyclic rings A and E were present.…”

“…In contrast, a large volume of partial syntheses and syntheses of core subunits of varying structural and stereochemical complexities have been reported. 11 Except for our earlier reports, 6,12 to the best of our knowledge, no synthetic studies have been disclosed toward the calyciphylline B family of alkaloids.…”

Recent Progress in the Chemistry of Daphniphyllum Alkaloids

“…Asymmetric Synthesis of the ABCE Ring System of Calyciphylline B-type Alkaloids. In 2016, Hanessian and co-workers 167 reported a model tetracyclic core structure of calyciphylline B-type alkaloids (Scheme 51). The synthesis commenced from the previously reported all-syn 3,4-disubstituted L-proline ester derivative 377, which was synthesized in eight linear steps from 4-(R)-hydroxy-L-proline.…”

Short Approach toward the Nonracemic A,B,E Tricyclic Core of Calyciphylline B-Type Alkaloids

“…Several other natural products possessing the same skeleton have since been identified. Surprisingly, synthetic efforts toward members of this family remained essentially nonexistent until recent work from the Hanessian group, ultimately leading to the synthesis of isodaphlongamine H …”