Asymmetric total synthesis of pyrenolide D through “Pd-Au” cascade lactonization and spirocyclization reaction: Adventitious photoisomerization method to synthesis naturally occurring γ-(Z)/(E)-alkylidenebutenolides through bimetallic cascade cycliza | Poster Board #340

The phytogenic fungus Pyrenophora teres (Diedicke) Drechsler (IFO 7508) is the source of a number of fungal metabolites with broad-spectrum biological activities. Three of these metabolites, pyrenolides A-C, have ten-membered keto-lactone structures and exhibit potent growth inhibition and morphogenic activity toward fungi (Figure 1). A fourth metabolite, pyrenolide D, is structurally distinct from the other members of this family and has been isolated from the same fungus. It possesses a spiroketal chiral center along with a highly oxygenated tricyclic spiro-γ-lactone. In this pursuit, the total synthesis of pyrenolide D will be presented from D-Xylose in a chiral pool strategy which is beneficial in terms of its high efficiency, operational ease, and higher yields more shortly and most efficiently. The key reactions employed are Wittig/Michael/instant lactonization and bimetallic cascade cyclization consisting of a “Pd-Au” catalytic system employed to construct sugar appended γ-Z-alkylidenebutenolide core. Total synthesis of naturally occurring [5,5] oxa-spiro- γ-lactone pyrenolide D was achieved through 5-endo-trig cyclization from this intermediate.(Scheme 1)

A general and flexible visible light-induced photoisomerization method of γ-(Z)-alkylidenebutenolides to its corresponding E-components was reported in this article. Initially, a series of naturally occurring enantiopure γ-(Z)-alkylidenebutenolides was synthesized by employing a “Pd-Cu” bimetallic cascade cyclization protocol. In the later part, the synthesized γ-(Z)-alkylidenebutenolides were photoisomerized in the presence of a triplet photosensitizer to γ-(E)-alkylidenebutenolides in reasonably accepted yields. Total synthesis of goniobutenolides, hygrophorones, ramariolide D, melodorinols/acetyl-melodorinols, versicolactones, and phomsopolidones was achieved by employing the developed methods.(Scheme 2)