Augustamine

Augustamine, [109]. The stannylated inline 353 utilised in the synthesis of (-)-amabiline (346) also served as the advanced intermediate for the preparation (Scheme 65) of (-)-augustamine (493) [93,94]. Thus, treatment of the mixture of the lithium salts 355 and 356 with iodomethane furnished a 43 1 mixture of the two tertiaiy amines 494 and 495 respectively. The cij-diol, obtained on acid hydrolysis of the former was converted into the ortho ester 496, which on exposure to methanesulphonic acid underwent cyclisation via the carbenium ion 497 to (-)-augustamine (493) in 76% yield. 

Scheme 65. Synthesis of (-)-augustamine (continued next page).

Some novel additions to this family of alkaloids include ryllistine (579), the first 4-oxygenated norbelline alkaloid (6) augustamine (582) (26) latifine (594), a biogenetic isomer of cherylline (595) (221) the O-glycosyl alkaloids lycorine-... 

Augustamine (582), which was isolated from Crinum augustum Rox., represents a new structural type of alkaloid in the family Amaryllidaceae (26), and its structure was deduced by extensive H- and 13C-NMR studies, which resulted in the complete assignments of the H- and 13C-NMR spectra, together with an analysis of its mass spectrum. The assignment of the cis ring fusions were based on analysis of vicinal coupling constants of the relevant protons. 

In more recent times, 2-azaallyl anions have been much more conveniently generated by the transmetallation of 1-aminoalkylstannanes. Thus for the forward synthesis of (—)-augustamine, this would mean that the 2-azaallylstannane 5 would be the key intermediate needed. 

The Pearson syntheses of (—)-augustamine and (—)-amabiline by a common strategy are very noteworthy. They brilliantly show how the awesome power of intramolecular 2-azaallyl anion-olefin cycloadditions can be marshalled for the rapid assembly of complex pyrrolidine alkaloids with excellent efficiency and atom economy. 

The complete mechanism of the conversion of 2 into (—)-augustamine is shown in Scheme 16.5. 

Machocho AK, Bastida J, Godina G, Viladomat F, Brun R, Ghhabra SG (2004) Augustamine type alkaloids from Crinum kirkii. Phytochemistry 65 3143... 

Pearson and Lovering have completed the first synthesis of the amaryllidaceae alkaloids (—)-amabiline 281 and ( —)-augustamine 280, from the common intermediate 279 using intramolecular [3+2] 2-azaallyl anion based methodology (Scheme 45). In the synthesis of 281 the intermediate is trapped by a Mannich type electrophilic aromatic substitution, while for 280, trimethyl orthoformate is used for electrophilic aromatic substitution-based cyclization. 

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