An intramolecular Diels-Alder reaction of the enol ester derived from 2-acetylpyridine and sorbic anhydride gave the cycloaddition product, stereoselectively, which was further converted into the key intermediate for the synthesis of securinine.Securinine, 1 a member of the Securinega family of alkaloids having a tetracyclic indolizidine skeleton with an α,β-unsaturated γ-lactone, was originally isolated from Securinega suffruticasa, 2 and its structure was determined by chemical and spectroscopic studies, 3,4 and also by X-Ray crystallographic analysis 5 as shown in Figure 1. N O O H Figure 1. The structure of securinine.Since this alkaloid has been shown to exhibit a stereospecific GABAA receptor antagonist activity, a number of syntheses and synthetic approaches were developed with the hope of understanding the shape of the GABAA receptor site. 6 To date, only two total syntheses of securinine have been reported. 7 The first total synthesis of securinine was published by Horii and co-workers in 1967, 7a where cyclohexane-1,2-dione was employed as the A-ring precursor and 2-lithiopyridine was introduced as the C-ring moiety. Although a number of synthetic approaches to this alkaloid were developed after Horii's synthesis, most of them could not reach to its total synthesis. Very recently, a concise total synthesis of securinine was achieved by using a ring closing metathesis leading to the construction of the A-ring, as a key reaction by Liras and co-workers. 7b Due to the attractive biological activity and also its unique structural feature, we are also interested in developing a novel strategy for the synthesis of securinine, in N Boc O N Boc O O N Boc O O Scheme 2. 1) LDA, THF 2) sorbic anhydride 10 11 12Although the stereochemistry of the products could not be determined at this stage, the major product was Treatment of the diol (26) with thiocarbonyldiimidazole afforded the thionocarbonate (27) in 85% yield.Reductive deoxygenation of 27 with bis(1,5-cyclooctadiene)nickel(0) [Ni(COD) 2 ], 12 provided the olefin (28), mp 138°C, in 90% yield. Finally, the diene system was introduced by phenylselenylation of 28 in the presence of lithium diisopropylamide, followed by oxidative elimination of the selenide (Scheme 6).Since the compound (29) was already converted into securinine by Horii and co-workers, 7a this synthesis constitutes its formal synthesis.