The fusion of click chemistry, fluorogenic chemodosimetry and a solid support offers advantages in identifying compounds in complex natural product mixtures.

While numerous studies pertaining to the total synthesis of Cephalotaxus alkaloids have been reported, only two strategies have been reported to date for the successful synthesis of the C-11 oxygenated subset, due to the additional synthetic challenge posed by the remote C-11 stereocenter. Herein, we report the collective asymmetric total synthesis of C-11 oxygenated Cephalotaxus alkaloids using achiral proline both as as tarting material and as the only chirality source.A tetracyclic advanced intermediate was synthesized in ah ighly stereoselective manner from l-proline in 8s teps involving sequential chirality transfer steps such as ad iastereoselective N-alkylation, stereospecific Stevens rearrangement and intramolecular Friedel-Crafts reaction via an unusual O-acyloxocarbenium intermediate.F rom ac ommon intermediate,t he asymmetric total synthesis of six C-11 oxygenated Cephalotaxus alkaloids was completed by as eries of oxidation state adjustments.

The first asymmetric synthesis and configurational elucidation of (−)-cephalezomine G was achieved. The highly functionalized Cα-substituted proline derivative was prepared from d-proline as the only chiral source via a C → N → C chirality transfer method consisting of stereoselective N-allylation and [2,3]-Stevens rearrangement. The azaspiranic tetracyclic backbone was constructed using ring-closing metathesis and the Friedel–Crafts reaction. Two contiguous hydroxyl groups were introduced in the later stages.

Asymmetric synthesis of α‐substituted proline derivatives has been accomplished by an efficient chirality‐transfer method. High diastereoselectivity of the N‐alkylation of the proline ester (C→N chirality transfer) was achieved when a 2,3‐disubstituted benzyl group was used as the N‐substituent. DFT calculations provided a mechanistic rationale for the high degree of stereoselectivity. The generated N‐chirality of the quaternary ammonium salt was transferred back to the α‐carbon through a stereoselective [2,3]‐Stevens rearrangement (N→C chirality transfer) to give α‐substituted proline ester.

The first total syntheses of (-)-isowondonin A and (-)-isowondonin B, which are unusual imidazole marine alkaloids, has been accomplished through the development of methods for the selective formation of styryl sulfate group and regioselective alkylation of the imidazole. Application of the Noyori asymmetric hydrogenation of ketones allows the asymmetric synthesis. These results in conjunction with ECD calculations led to the determination of the absolute configuration of isowondonins.