Total Synthesis of Maoecrystal P: Application of a Strained Bicyclic Synthon

Abstract

A new strategy was devised for the total synthesis of highly oxidized ent-kauranoids. A highly regio- and diastereoselective intermolecular Diels-Alder cycloaddition involving a diene embedded in a substituted bicyclo[4.1.0] skeleton was used to assemble all carbon centers but C17 of the target molecule at an early stage of the synthesis. Subsequent synthetic steps, including redox manipulations, SmI -mediated cyclization, and isomerization reactions, afforded the antitumor natural product maoecrystal P.

Samarium(ii) iodide-mediated reactions applied to natural product total synthesis

“…In 2018, Luo and co-workers 99 introduced a new strategy for the total synthesis of maoecrystal P 225 with 27 steps from commercially available 2-bromocyclohex-2-one 222. The total synthesis of maoecrystal P 225 included a highly regio- and diastereoselective intermolecular Diels–Alder cycloaddition, redox manipulations, a SmI 2 -mediated carbonyl–alkene cyclization, and isomerization reactions.…”

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

“…The diterpene maoecrystal P, isolated from the Chinese medicinal plant Isodon eriocalyx, was previously reported to show significant cytotoxic activity. 44 Scheme 25 Intermolecular Diels-Alder reaction in the total synthesis of maoecrystal P.…”

“…Maoecrystal P, isolated from the Chinese medicinal plant Isodon eriocalyx was previously reported to show significant cytotoxic activity. 44…”

“…Scheme44 The cycloaddition between -humulene (171) and ribose-derived vinyl ketone 172 represents the key step in the synthesis of the skeletons of xenovulene A and sterhirsutins A and B…”

Asymmetric Total Syntheses of 8,9‐Seco‐ent‐kaurane Diterpenoids Enabled by an Electrochemical ODI‐[5+2] Cascade

“…Guided by the biosynthetic hypothesis for 2-6, we planned to establish a streamlined synthetic approach to (À)-shikoccidin (7; Scheme 1 b). Surprisingly, although substantial progress was made toward the total syntheses of entkauranoids, [7][8][9] their C9-oxygenated congeners have not been conquered. We reasoned that (À)-7 would be assembled from 8 through a [2,3]-sigmatropic rearrangement of the corresponding allylic selenoxide [10] to forge the tertiary Scheme 1. a) Structures and proposed biogenetic pathways of 8,9seco-ent-kauranoids 1-6; b) our retrosynthetic plan toward (À)-shikoccidin (7).…”