ANaPSyS - Artifical Natural Products System Synthesis
- FB Chemie
|(2019): Structure-Pattern-Based Total Synthesis Chemistry - A European Journal. Wiley. 2019, 25(46), pp. 10782-10791. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201901308||
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.
|(2019): Gram‐scale Total Syntheses of Sarpagine Alkaloids and non‐Natural Derivatives Chemistry - A European Journal. 2019, 25(11), pp. 2704-2707. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201805644||
This work describes the total synthesis of 3 members of the sarpagine alkaloid family and 10 non‐natural congeners via an improved synthetic sequence which was designed to the point of gram‐scale production of materials suited for SAR‐studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated stemona alkaloid parvineostemonine (34), posing a showcase for efficient synthetic design.
|(2018): Total Synthesis of Parvineostemonine by Structure Pattern Recognition : A Unified Approach to Stemona and Sarpagine Alkaloids Chemistry - A European Journal. 2018, 24(16), pp. 3994-3997. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201800365||
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.
|(2016): Total Syntheses of Vellosimine,N-Methylvellosimine, and 10-Methoxyvellosimine and Formal Synthesis of 16-Epinormacusine B through a [5+2] Cycloaddition European Journal of Organic Chemistry : EurJOC. 2016, 2016(28), pp. 4893-4899. ISSN 0075-4617. eISSN 0365-5490. Available under: doi: 10.1002/ejoc.201600870||
Total Syntheses of Vellosimine,N-Methylvellosimine, and 10-Methoxyvellosimine and Formal Synthesis of 16-Epinormacusine B through a [5+2] Cycloaddition
To date, more than 100 members of the sarpagine alkaloid family have been isolated. Their structural variations originate from oxidative transformations of the carboskeleton and the presence of both absolute configurations at the C-16 atom, which is established in the course of their biosynthesis. More than 40 sarpagine alkaloids belong to the either the 16-regular or 16-epi subgroups, depending on the stereochemistry at C-16. Herein, we report the formal synthesis of 16-epinormacusine B, a member of the 16-epi group, by using our well-established generalized strategy for the total synthesis of these alkaloids. Furthermore, we provide the synthetic details and pitfalls of the asymmetric total syntheses of vellosimine, N-methylvellosimine, and 10-methoxyvellosimine, all members of the 16-regular group.
|Laufzeit:||01.04.2016 – 31.03.2021|