Azabicyclo octane skeleton

The synthetic work above on the securinine-t5rpe alkaloids carried out to date has been directed mainly along one particular avenue of approach. In view of the intrinsically interesting structure and potentially useful biological activity of these alkaloids other synthetic attacks are to be expected particularly since new and intriguing methods for construction of the 6-azabicyclo[3,2,l]octane skeleton are being rapidly developed (73, 74). 

Several examples of SNAr reactions using sodium hydride to generate the necessary alkoxide have been reported. An interesting example of an intramolecular variation was reported using -lactams to give the 4-oxa-7-azabicyclo[4.2.0]octane skeleton (eq 33). ... 

The biochemical properties of epibatidine have been Modifications to the compared to the ring-enlarged 8-azabicyclo[3.2.1]octane azabicycioaikane skeleton derivative homoepibatidine and several 2-azabicyclo-[2.2.1]heptanes (Cox et al., 2001). 

TA belong to a class of small molecules characterized by a derivatized tropane ring skeleton (8-methyl-8-azabicyclo[3.2.1]octane). Hydroxylated tropane (tropine) is esterified with diverse organic acids often representing structural analogues of, e.g. tropic, benzoic or mandelic acid (Fig. 1). Manifold variations are found either in natural sources or as (semi-) synthetic active pharmaceutical ingredients (API) with individual optimized properties. 

When an amine is placed in an internal position, more complex frameworks could be assembled through the radical/polar crossover tandem sequence. Depending on the substitution pattern, pyrrolizidines [220], indolizidines [221], and azabicyclo[3.2.1] octanes [221] skeletons could be prepared [222]. 

The direct synthesis of the morphinan skeleton (107) from (105) involves the intramolecular ring opening by the enolate anion of the in situ generated aziridine cation (106) (Scheme 41) <88J0C2144>. Compound (108) was found to rearrange thermally to the thermodynamically favored azabicyclo-[3.3.1]octane (110) via the aziridinium ion (109) (Scheme 42) <93CC758>. 

The tropane alkaloids comprise a large well-defined structurally group of natural products, occurred mainly in family Solanaceae but also are found in the families Convolvulaceae, Erythroxylaceae, Proteaceae, Rhizophoraceae, etc. [1], Common structural element of these alkaloids is the tropane skeleton, crnisisting of a pyrrolidine and piperidine ring sharing the nitrogen atom and two carbon atoms. The systematic name of the tropane skeleton is 8-methyl-8-azabicyclo[3.2.1.]octane (Fig. 12.1). Currently, the number of these alkaloids is more than 200 [2-4]. 

Tropane alkaloids are characterized by the bicyclic tropane skeleton (A-methyl-8-azabicyclo[3.2.1.]octane Fig. 3.13). The scientific history of the tropanes started already in the beginning of the nineteenth century (see also above). The famous... 

Scheme 5 illustrates the light-induced addition of AT-methylpyrrolidine to butenolides. By use of trimethylsilylpyrrolidine in a similar way, followed by base treatment, a 4-substituted 1-azabicyclo[3.3.0]octan-2-one, the ring skeleton of die alkaloid lindelofidine, can be obtained. 

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