Synthesis of nagilactone

The first synthesis of nagilactone F was carried out by Hayashi et al. [83] starting from (+)-0-methylpodocarpic acid 158 in 23 steps (2% overall yield). The main characteristics of this synthesis include the transformation of the aromatic ring into the 5-lactone ring, the a arrangement (equatorial) of the isopropyl group by photochemical cyclization, as well as the construction of the y-lactone using radical conditions (Scheme 14). 

The same strategy used by Barrero et al. for synthesis of the fungic metabolite LL-Z1271a (63) was used to synthesize nagilactone F (55). Thus, starting from the mixture of communic acids, lactol 99 is achieved, an immediate precursor of both 55 and epimer 165, which are obtained by treatment with isopropylmagnesium bromide. Thus, the synthesis of nagilactone F (55) is completed, with an overall yield of 10%. (Scheme 15). 

Total synthesis of nagilactone F, a biologically active norditerpenoid dilactone isolated from Podocarpus nagi. Hayashi, Y. Matsumoto, T. Nishizawa, M. Togami, M. Hyono, T. Nishikawa, N. Uemura, M. J. Org. Chem. 1982, 47, 3428-3433. 

Enantioselective synthesis of nagilactone F via vinylsilane-terminated cationic cyclization. Burke, S.D. Kort, M.E. Strickland, S.MS. Organ, H.M. Silks, L.A., III. Tetrahedron Lett. 1994,35,1503-1506. 

As a first approach to the synthesis of nagilactone 296, a norditer-penoid isolated from Podocarpaceae, which inhibit the expansion and mitosis of plant cells, an intramolecular Diels-Alder reaction of allene 1,3-dicarboxylic acid esters was used. The cyclization of 297 afforded the 8-lactone 298, rather than the y-lactone 299 [85JCS(P1)747]. 

Burke et al. [84] synthetised nagilactone F (55) by a polyenic cyclization initiated with acetal and concluded with vinylsilane, giving an overall yield of 6%. The key steps in this synthesis were the coupling of substrates 166 and 167 with control of the absolute and relative stereochemistry, the cationic biscyclization to form the intermediate tricyclic trans-anti-trans 169 and the formation of the D ring by regio-selective intramolecular remote functionalization. 

---