Total Syntheses of Heimiol A, Hopeahainol D, and Constrained Analogues

Abstract

IDSI to the Rescue Use of a carefully designed cascade process empowered by the unique iodonium-reagent IDSI [(Et2SI)2Cl•SbCl6] provided the means to construct the entire [3.2.2]-bicyclic core of both targets in a single, stereocontrolled operation. Use of strain energies assisted in the completion of the natural products, with the overall strategy proving applicable as well to the preparation of a number of unique [3.2.1]-dimeric and highly strained resveratrol-based compounds.

A Scalable Biomimetic Synthesis of Resveratrol Dimers and Systematic Evaluation of their Antioxidant Activities

“…While construction of these molecules in such a fashion would support their proposed biogenesis, efforts to date have resulted in low yields and/or complex mixtures of products. Recognizing this shortcoming, Snyder and co‐workers developed powerful de novo strategies towards resveratrol dimers5b,c, 6c,d and higher‐order oligomers 7. These impressive studies prompted a number of subsequent syntheses, including innovative approaches from the Nicolaou/Chen,6a Sarpong,6b and Studer5f groups.…”

Structural Revision and Total Synthesis of Caraphenol B and C

“…7 To date, we have synthesized over 20 different natural products at the dimeric, trimeric, and tetrameric levels encompassing a range of different types of ring systems, including indanes, 7-membered rings, dihydrofurans, and bicyclic frameworks. It was in this vein that the structures of caraphenols B and C ( 1 and 2 ), 8 two isolates from the dried roots of Caragana sinica (which has been used as a folk medicine in China to treat hypertension and contusions), caught our attention.…”

“…11 Indeed, other members, such as ampelopsin D ( 3 ) 12 and quadrangularin A ( 4 ) 13 place their labelled B- and C-aryl rings trans . As we have recently shown, 7ab indane-based materials such as 3 and 4 can subsequently be converted into other dimeric cores like ampelopsin F ( 5 ) 12 and pallidol ( 6 ) 14 through electrophilic activation in a potentially biomimetic process. To the best of our knowledge, however, no material yet isolated can similarly be traced to the unique stereochemistry of caraphenol B and C; other diastereomers of 5 and 6 exist, such as 7 , 7d,8 but they reflect alteration in double bond geometry in what would be similar electrophile-induced cyclizations of indane starting materials, not variations in core ring stereochemistry.…”

“…Our efforts to forge the all- cis stereochemical arrangement of the proposed structure of caraphenol B ( 1 ) began from permethylated ampelopsin D ( 9 ) 7ab as shown in Scheme 1. Following a standard reaction sequence involving dihydroxylation of its lone olefin, oxidation of the resultant secondary alcohol under Swern conditions, and elimination using p -TsOH in benzene at 80 °C, we accessed α,β-unsaturated ketone 10 in 45% overall yield.…”

“…Our route to our revised structure for caraphenol B (i.e. 22 ) is shown in Scheme 2, wherein initial operations afforded compound 20 in 5 standard chemical steps 20 from protected paucifloral F ( 18 ) 7ab by way of aldehyde 19 . The stereochemistry of this material ( 20 ) could be isomerized to the all- trans arrangement of 21 through the action of NaOMe in MeOH at 65 °C, providing a compound with coupling constants and proton positionings similar to that reported for natural caraphenol B.…”