Jatrophone Analogues: Synthesis of cis- and trans-Normethyljatropholactones

Article abstract of DOI:10.1021/jo00139a011

This, a full account, discloses an efficient, convergent synthesis of two novel analogues of the macrocyclic antitumor diterpene jatrophone (1).We term these analogues cis- and trans-normethyljatropholactone (2 and 3, respectively).Our approach in each case begins with the bis(trimethylsilyloxy) ketone 7 and the requisite acetylenic or trans ester-aldehyde, 8 or 12a.Application of our previously developed 3(2H)-furanone synthetic protocol consisting of aldol condensation of the lithium enolate derived from 7 with the respective ester-aldehydes 8 or 12a, followed byoxidation (Collins reagent) and acid-catalyzed cyclization-dehydration, affords spirofuranone 6c and 14c, respectively, in 52percent and 45percent overall yields.Sodium borohydride reduction, ester hydrolysis, and closure of the macrolide by employing the conditions of Mukaiyama (i.e., 1-methyl-2-chloropyridinium iodide-/Et3N/CH3CN) in the case of spirofuranone 14a leads directly to trans-normethyljatropholactone (3), while completion of cis-normethyljatropholactone (2) requires first semihydrogenation; the latter was accomplished by employing PdSO4 in pyridine as the catalyst.The overall yields of 2 and 3, based on 7, were 23percent and 21percent, respectively.