Synthetic studies on the ingenane diterpenes. Inter- and intramolecular [6 + 4] tropone-diene cycloaddition reactions

Abstract

Synthetic Studies on the Ingenane Diterpenes. Interand Intramolecular [6 + 4] Tropone-Diene Cycloaddition Reactions1Summary: Thermally allowed interand intramolecular [6 + 4] tropone-diene cycloadditions have been employedfor the construction of intermediates in the synthesis of the cocarcinogenic diterpene ingenol.(9) While this manuscript was in preparation, another example of an intramolecular [6 + 4] tropone cycloaddition surfaced: Funk, R. L., personal communication.(10) 2-Substituted tropones are relatively difficult to prepare. Compound 9 is available in 61% from the reaction of 2-chlorotropone11 and the Grignard reagent derived from l-bromohept-4,6-diene. Details of this procedure will be reported in a separate paper: Rigby,

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…However, the unusual in/out stereochemistry, 237 or trans intrabridgehead stereochemical configuration, of the bicyclo[4.4.1]undecane motif represents a particularly daunting difficulty. 238 − 250 In light of these challenges, a number of total syntheses of ingenol ( 2 ) have been reported. 38 , 251 − 261 …”

“…The polyoxygenated tetracyclic core of ingenol ( 2 ) features several challenges, including the stereogenic triol unit of the A and B rings and a quaternary carbon stereocenter. However, the unusual in/out stereochemistry, or trans intrabridgehead stereochemical configuration, of the bicyclo[4.4.1]­undecane motif represents a particularly daunting difficulty. − In light of these challenges, a number of total syntheses of ingenol ( 2 ) have been reported. ,− …”

Dynamical Trajectory Study of the Transannular [6+4] and Ambimodal Cycloaddition in the Biosynthesis of Heronamides

“…First discovered in the mid-1960s, the [6+4] cycloaddition is a type of pericyclic reaction that involves 10 π-electrons. − During the past half century, its reaction mechanism and synthetic utility have been studied by various research groups; − [6+4] cycloadditions usually need to compete with possible Diels–Alder reactions, since the formed [6+4] adducts, in many cases, will undergo Cope rearrangements to generate the more stable [4+2] products to release the strain associated with 10-membered rings . As shown in Figure , Capon and co-workers discovered several natural products in 2010, heronamide C, which features a 20-membered polyene macrolactam, heronamide A ([6+4] product), and heronamide B .…”

Structure of a synthetic tricyclic dione with an ingenol-like ring system

“…)02 ,.,.,f.,'c~o ORTEP drawing (at 50% probability) of 8,9,10,11-tetrahydro-10-methyl-(3aa,8a, 10a)-3a,8-methano-3aH-cyclopentacyclodecene-2,12(3H)-dione showing the adopted labeling. Moore & Rege, 1986). The structure of ingenol triacetate, a modified derivative of the natural product ingenol-3'hexadecanoate, has been examined (Zechmeister, Brandl & Hoppe, 1970;Paquette, Nitz, Ross & Springer, 1984).…”