Delphinine synthesis

The chemistry of the diterpenoid alkaloids, rather than their structure elucidation by physical methods, has attracted more interest during the year covered by this Report. While several new alkaloids have been reported, most of the research on these polycyclic, polyfunctional bases has involved chemical conversions and synthetic methods. Most notably, Wiesner s group at New Brunswick, Canada, has reported a fourth-generation synthesis of the delphinine-type alkaloids. That this marvel of synthetic engineering accomplishes the stated goals1 of a highly efficient, fully regio- and stereo-specific synthesis of these complex natural products is abundantly clear. 

A New Synthesis of Napelline.—Workers at New Brunswick have reported an excellent stereospecific synthesis of napelline (70), based on their fourth generation methods that were developed in the synthesis of several delphinine-type alkaloids.59 These methods had previously been explored with model compounds, and employ the rearrangement of a denudatine system to a napelline system.60 The starting material (123) for this synthesis was prepared by the route analogous to that used for the preparation of 13-deoxydeIphonine.60,61... 

Aconitine Type. In an ingenious set of interpretations, Biichi and Wiesner and their co-workers showed that the chemistry of aconitine and delphinine was consistent with a lycoctonine skeleton for these alkaloids. However, to provide a rigorous structure proof, synthesis of some of the unusual degradation products seemed desirable. (An X-ray crystallographic analysis of desmethanol aconinone... 

The major synthetic effort in this area has been directed at the partially aromatic degradation products such as (112) from delphinine. A synthesis of a racemic model compound (113 = H) was recently presented in detail ... 

Over the last ten years Professor Wiesner and his co-workers at the University of New Brunswick have made important contributions to the synthesis of delphinine (31) and related diterpenoid alkaloids (147-150). 

This synthesis represents an outstanding achievement and provides a clarification of the structure of delphinine and related aconitine-type alkaloids. 

In 1973 Wiesner and his colleagues reported (161) a new synthetic route for the construction of the substituted C/D ring system of delphinine-type alkaloids. This process was based on a previous photochemical synthesis of the atisine skeleton (162). 

Several new synthetic approaches to the atisine and veatchine alkaloids have been reported, and a detailed account of the synthesis of an optically active relay intermediate in the synthesis of delphinine has appeared. 

Aconitine-type Alkaloids Syntheses Directed toward Delphinine.— The New Brunswick group have published in detail their work on the stereoselective total synthesis of optically active (62), an advanced relay compound in the synthesis... 

The stereoselective total synthesis of the delphinine degradation product (158) has been described. The key stages involved the conversion of the tetralone (152) into the aldehyde (153) and its ring-closure to (154). This product was then converted into the compound (155), which underwent cyclization to form the lactam (156) in the presence of potassium cyanide. On acid hydrolysis, this was converted into the lactam (157), which was in turn transformed into (158), the... 

Research studies on the aconite alkaloids started at the beginning of the nineteenth century, and aconitine was isolated from Actinidia napellus in 1833. As for the Aconitum plants of Japan, Shimoyama made the first report in 1882, and the plain chemical structure of aconitine was reported in the 1950s [4]. The stereochemistry, including absolute configuration, of the aconitine skeleton was determined when the total synthesis delphinine, an aconitine-related alkaloid, was achieved in 1972 [5-7]. 

Wiesner, K., T. Y. R. Tsai, K. Huber, S. E. Bolton, and R. Vlahov Total Synthesis of Talatisamine, a Delphinine Type Alkaloid. J. Amer. Chem. Soc. 96, 4990 (1974). PRZYBYLSKA, M., T. Y. R. TsAi, and K. Wiesner Conversion of the Alkaloid Atisine into a Compound with the Lycoctonine Skeleton. Chem. Commun. 1975, 297. 

---