| Abstract
| - Full details of the synthesis of the fully elaborated aziridino[1,2-a]pyrrolidine substructure 2 of theantitumor agents azinomycins A and B are reported. Stereoselective bromination of dehydroamino acid 4provided control of olefin configuration in the final product, as a consequence of a stereospecific cyclizationof aziridine 3 onto the proximal β-bromoacrylate, which effected pyrrolidine ring introduction. Dehydroaminoacid 4 was constructed by olefination of aldehyde 5 with a glycine-based phosphonate. Two complementarysynthetic routes to 2 are presented. In the first route, the selectively protected C12/C13 diol system of thetargets was introduced into starting structure 6 in a stereocontrolled manner using Brown's (γ-alkoxyallyl)diisopinocampheylborane reagent system. Transient protection of the C12 hydroxyl group of 48 as thetrimethylsilyl ether was used to prevent C13 acetate migration prior to cyclization. Deprotection of the C12hydroxyl following cyclization to the azabicyclic system afforded the extremely unstable core substructure 44,which could not be isolated, but was characterized in situ. In the second route, the racemic γ-alkoxystannane8 was added in a chelation-controlled manner to serinal derivative 9 under conditions of kinetic resolution forintroduction of the C12 and C13 stereogenic centers of the target. Phenylacetate and methoxyacetate esterswere used for C12 hydroxyl protection. This work represents the first synthesis of the intact core substructure44 of this novel class of natural products.
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