Abstract:The syntheses of members of a family of lindenane sesquiterpenoid [4+2] dimers led to the total syntheses of sarcandrolide J and shizukaol D. Inspired by a modified biosynthetic pathway, a cascade featuring furan formation/alkene isomerization/Diels-Alder cycloaddition was devised to construct the congested polycyclic architecture of the target molecules with the correct stereochemistry. This study presents a pioneering synthetic entry to this family of natural products and paves the way for fully exploring th… Show more
“…Following our long-standing interest in the syntheses of terpenoids 22 , we reported the first syntheses of lindenane sesquiterpenoid [4 + 2] dimers, sarcandrolide J and shizukaol D (type 2) in the guidance of our modified biosynthetic hypothesis (Fig. 1b) 6 . Recently, the Peng group reported their achievement of total syntheses of shizukaols A and E, types 1 and 2 [4 + 2] dimers, respectively, through the other modified biomimetic Diels–Alder reaction 7 .Fig.…”
Section: Introductionmentioning
confidence: 99%
“…However, no synthesis of type 3 [4 + 2] dimers has yet been reported, despite their predominant numbers accounting for more than four-fifths across the whole lindenane family. Notably, direct functionalization of the gem -disubstituted alkene on ring B failed to convert type 1 dimers into types 2 or type 3, because the inherent stereochemical control from the robust 3/5/6/5 backbone favors the undesired diastereomer 6,16 . Thus, a unified synthetic strategy is in demand to provide all the three types of lindenane [4 + 2] dimers and their synthetic analogs, by following the plausible [4 + 2] biosynthetic pathways with a common furyl diene and various dienophiles.…”
The dimeric lindenane sesquiterpenoids are mainly isolated from the plants of Chloranthaceae family. Structurally, they have a crowded molecular scaffold decorated with more than 11 stereogenic centers. Here we report divergent syntheses of eight dimeric lindenane sesquiterpenoids, shizukaols A, C, D, I, chlorajaponilide C, multistalide B, sarcandrolide J and sarglabolide I. In particular, we present a unified dimerization strategy utilizing a base-mediated thermal [4 + 2] cycloaddition between a common furyl diene, generated in situ, and various types of dienophiles. Accordingly, all the three types of lindenane [4 + 2] dimers with versatile biological activities are accessible, which would stimulate future probing of their pharmaceutical potential.
“…Following our long-standing interest in the syntheses of terpenoids 22 , we reported the first syntheses of lindenane sesquiterpenoid [4 + 2] dimers, sarcandrolide J and shizukaol D (type 2) in the guidance of our modified biosynthetic hypothesis (Fig. 1b) 6 . Recently, the Peng group reported their achievement of total syntheses of shizukaols A and E, types 1 and 2 [4 + 2] dimers, respectively, through the other modified biomimetic Diels–Alder reaction 7 .Fig.…”
Section: Introductionmentioning
confidence: 99%
“…However, no synthesis of type 3 [4 + 2] dimers has yet been reported, despite their predominant numbers accounting for more than four-fifths across the whole lindenane family. Notably, direct functionalization of the gem -disubstituted alkene on ring B failed to convert type 1 dimers into types 2 or type 3, because the inherent stereochemical control from the robust 3/5/6/5 backbone favors the undesired diastereomer 6,16 . Thus, a unified synthetic strategy is in demand to provide all the three types of lindenane [4 + 2] dimers and their synthetic analogs, by following the plausible [4 + 2] biosynthetic pathways with a common furyl diene and various dienophiles.…”
The dimeric lindenane sesquiterpenoids are mainly isolated from the plants of Chloranthaceae family. Structurally, they have a crowded molecular scaffold decorated with more than 11 stereogenic centers. Here we report divergent syntheses of eight dimeric lindenane sesquiterpenoids, shizukaols A, C, D, I, chlorajaponilide C, multistalide B, sarcandrolide J and sarglabolide I. In particular, we present a unified dimerization strategy utilizing a base-mediated thermal [4 + 2] cycloaddition between a common furyl diene, generated in situ, and various types of dienophiles. Accordingly, all the three types of lindenane [4 + 2] dimers with versatile biological activities are accessible, which would stimulate future probing of their pharmaceutical potential.
“…Remarkably, a wealth of seco D-lindenanes were reported within lindenane sesquiterpenoid [4 + 2] dimers, especially from the Sarcandra species, e.g., sarcandrolides [22,26]; and various Chloranthus plant species such as shizukaol species [27][28][29], chlorahololides [30,31], spicachloranthins E and F [32], and chlorajaponilides [33], among many others. The biosynthesis of dimeric lindenane sesquiterpenes is deemed to proceed via a Diels-Alder reaction with Δ 4,15 and Δ 5,6 representing the diene reactive unit [34]. Furyldiene lindenanes and, more generally speaking, molecules displaying these structural features rendering them prone to undergoing Diels-Alder addition, seem to be too unstable to be isolable [9].…”
Two new lindenane sesquiterpenes were obtained from the roots of Lindera myrrha. These compounds were structurally elucidated by HRMS data, extensive NMR analyses, and comparison between experimental and theoretical 13C-NMR data. Myrrhalindenane A is the first monomeric seco-d lindenane displaying a non-rearranged, cyclohexanic C-ring. Myrrhalindenane B is the second occurrence of an angular lindenane-sesquiterpene related to a C6-C7 lactonization.
“…In addition, most of these dimeric lindenane-type molecules show impressive bioactivities, such as remarkable cytotoxicity 9 , inhibition of the delayed rectifier K + current 10,11 , and antimalarial activities 12 . Therefore, the promising bioactivities and synthetic challenges arising from these unprecedented molecules have initiated a significant interest to synthetic chemists 13–30 . However, only one total synthesis of two dimeric members 30 and a number of relevant synthetic studies 13–29 have been achieved.…”
Section: Introductionmentioning
confidence: 99%
“…Therefore, the promising bioactivities and synthetic challenges arising from these unprecedented molecules have initiated a significant interest to synthetic chemists 13–30 . However, only one total synthesis of two dimeric members 30 and a number of relevant synthetic studies 13–29 have been achieved. In 2017, Liu and coworkers reported the first total syntheses of the dimeric shizukaol D ( 3 ) and sarcandrolide J ( 4 ) 30 through a cascade protocol featuring furan formation/alkene isomerization/Diels–Alder reaction.…”
Shizukaols possess a common heptacyclic framework containing more than ten contiguous stereocenters and potential biological activities. Here we report that the total syntheses of shizukaols A (1) and E (2), two lindenane-type dimers from the Chloranthaceae family, are achieved via a modified biomimetic Diels–Alder reaction. The common crucial biomimetic diene 23 and ethylene species (6, 17) are obtained through either a highly Z-selective olefination of α-siloxy ketone with ynolate anions or an intramolecular Horner–Wadsworth–Emmons olefination from commercially available Wieland–Miescher ketone (7). This synthetic approach here opens up practical avenues for the total syntheses of the intriguing Chloranthaceae family members, as well as the understanding of their relevant biological action in nature.
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