Ten-Step Asymmetric Total Synthesis of (+)-Pepluanol A.

The first asymmetric synthesis of pepluanol A (1) is presented. The synthesis route is very concise (10 steps) and features a Curtin-Hammett-driven stereoconvergent intramolecular Diels-Alder reaction. A Nozaki-Hiyama-Kishi reaction comprises the connective step, bringing together the seven-membered enone system bearing the dienophile and the diene in the side chain. Subsequent stereoconvergent IMDA reaction furnishes the carboskeleton of the natural product in only 7 steps. The reactions were carried out on a gram scale up to an advanced intermediate and including the stereoconvergent intramolecular Diels-Alder reaction.

Structure-Pattern-Based Total Synthesis.

In this article the concept of structure-pattern-recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target-oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.

Gram-Scale Total Synthesis of Sarpagine Alkaloids and Non-Natural Derivatives.

This work describes the total synthesis of three members of the sarpagine alkaloid family and ten non-natural congeners through an improved synthetic sequence, which was designed for gram-scale production of materials suited for structure-activity relationship (SAR) studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated Stemona alkaloid parvineostemonine (34), providing a showcase for efficient synthetic design.

Total Synthesis of Parvineostemonine by Structure Pattern Recognition: A Unified Approach to Stemona and Sarpagine Alkaloids.

Through structure pattern recognition based total synthesis we designed a synthesis in which two biogenetically unrelated natural product families (Stemona- and Sarpagine alkaloids) share 50 % of their synthetic sequence. In this report, the efficiency of such a strategic approach is demonstrated in the total synthesis of the Stemona alkaloid parvineostemonine, proceeding through a privileged intermediate that we have previously transformed into biogenetically completely unrelated Sarpagine alkaloids. In addition, we capitalized on the symmetry properties of the privileged intermediate, which was obtained as two regioisomers. After their separation by column chromatography the two regioisomers were converted to the corresponding pair of enantiomers by one transformation. To the best of our knowledge, this feature (conversion of regioisomers to enantiomers) has never been applied to natural product synthesis, and proved to be very valuable, since it allowed to obtain both optical antipodes of parvineostemonine in a single synthetic campaign. This not only enabled the determination of the previously undisclosed absolute configuration of the natural product, but gave 60-200 mg amounts of both enantiomers of the natural product.

Development of a ß-C-H Bromination Approach toward the Synthesis of Jerantinine E.

The development of an asymmetric and highly convergent three-component synthesis of the functionalized ABC ring system of the Aspidosperma alkaloid jerantinine E is reported. The presented synthetic strategy relies on our recently developed method for the one-pot ß-C-H bromination of enones, which allows for rapid construction of the tricyclic tetrahydrocarbazolone core via a palladium-catalyzed amination and oxidative indole formation. Moreover, a secondary amine building block that contains all carbon atoms of the D and E ring of the natural product could be installed in three additional steps.