Improved Synthesis of Methyl 7,7-Ethylenedioxy-3-methyl-9-oxobicyclo[3.3.1]non-3-ene-1-carboxylate, Intermediate for the Synthesis of Huperzine A Analogues

Huperzine A, A Potential Therapeutic Agent for Treatment of Alzheimer's Disease

“…Compound 4 could be obtained from α− carbomethoxy-or phenylsulfinyl cyclohexane-1,4-dione monoketal 5 . A couple of bicyclo [3.3.1]nonane or nonene compounds 6, 7, 8 and 9 were prepared [37,38,39,40]. These intermediates have been…”

“…The low yield of endocyclic alkene 23 is related to the configurations of mesylates 22, since the mesyloxy group and the adjacent hydrogen in 22 may not adopt a trans-diaxial orientation for base-induced elimination to alkene23 [38]. In the preparation of HupA analogues by author's group, acrolein was used in Michael-aldol reaction, two aldol products were separated by column chromatography to produce axial hydroxyl compound 30 and equatorial hydroxyl compound 31.…”

Huperzine alkaloids: forty years of total syntheses

“…In 2000, the Camps group reported their work on the formal synthesis of (±)-huperzine A (Scheme 23). 59,60 A Michael addition-aldol reaction of b-keto ester 104 with methacrolein generated the bridged structure. The formation of its derived thiocarbonate, followed by pyrolytic syn-elimination, generated the olen product 105.…”

Development of a Large-Scale Synthetic Route to Manufacture (−)-Huperzine A

“…Primarily to facilitate the synthesis of huperzine A analogues, Camps et al developed a different strategy for the synthesis of huperzine A, forming the bridged ring structure first, before elaborating the pyridine moiety. , However, this approach did not appear to offer any advantage in yield or potential for scale-up, and the separation of isomers proved difficult and required column chromatography.…”