ChemInform Abstract: Acetogenic Isoquinoline Alkaloids. Part 114. The Atropo-Divergent Preparation of Axially Chiral Biaryls Through the ′Lactone Methodology′: Total Synthesis of Korupensamine B.

G. BRINGMANN; M. OCHSE

doi:10.1002/chin.199908243

ChemInform Abstract: Acetogenic Isoquinoline Alkaloids. Part 114. The Atropo-Divergent Preparation of Axially Chiral Biaryls Through the ′Lactone Methodology′: Total Synthesis of Korupensamine B.

ChemInform ◽

10.1002/chin.199908243 ◽

2010 ◽

Vol 30 (8) ◽

pp. no-no

Author(s):

G. BRINGMANN ◽

M. OCHSE

Keyword(s):

Total Synthesis ◽

Isoquinoline Alkaloids ◽

Axially Chiral

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Total Synthesis of Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Based Drug Discovery

10.26434/chemrxiv.10251035.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Primali Navaratne ◽

Jenny Wilkerson ◽

Kavindri Ranasinghe ◽

Evgeniya Semenova ◽

Lance McMahon ◽

...

Keyword(s):

Drug Discovery ◽

Total Synthesis ◽

Ground State ◽

Chemical Space ◽

Modern Medicine ◽

The Novel ◽

Pharmaceutical Development ◽

Bioactive Component ◽

Axially Chiral ◽

New Directions

<div> <div> <div> <p>Phytocannabinoids, molecules isolated from cannabis, are gaining attention as promising leads in modern medicine, including pain management. Considering the urgent need for combating the opioid crisis, new directions for the design of cannabinoid-inspired analgesics are of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural (and unknown) isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are multiple reasons for thinking this: (a) ax-CBNs would have ground-state three-dimensionality akin to THC, a key bioactive component of cannabis, (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability, and (c) atropisomerism with respect to phytocannabinoids is unexplored “chemical space.” Herein we report a scalable total synthesis of ax-CBNs, examine physical properties experimentally and computationally, and provide preliminary behavioral and analgesic analysis of the novel scaffolds. </p> </div> </div> </div>

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Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products

Chemical Reviews ◽

10.1021/cr100155e ◽

2011 ◽

Vol 111 (2) ◽

pp. 563-639 ◽

Cited By ~ 679

Author(s):

Gerhard Bringmann ◽

Tanja Gulder ◽

Tobias A. M. Gulder ◽

Matthias Breuning

Keyword(s):

Natural Products ◽

Total Synthesis ◽

Axially Chiral

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Structural Investigation of a Configurationally Stable Seven-Membered Bridged Biaryl of Relevance for Atroposelective Biaryl Syntheses*

Zeitschrift für Naturforschung B ◽

10.1515/znb-2003-2-305 ◽

2003 ◽

Vol 58 (2-3) ◽

pp. 231-236 ◽

Cited By ~ 4

Author(s):

Gerhard Bringmann ◽

Robert-Michael Pfeifer ◽

Christian Rummey ◽

Thomas Pabst ◽

Dirk Leusser ◽

...

Keyword(s):

Total Synthesis ◽

Ring Opening ◽

Structural Investigation ◽

X Ray Diffraction ◽

Cleavage Reaction ◽

Perfect Agreement ◽

X Ray ◽

Ether Bridge ◽

Axially Chiral ◽

Aromatic Systems

The atroposelective ring opening of lactone-bridged biaryl systems is the key step in the total synthesis of a series of axially chiral biaryl natural products and useful reagents or catalysts for asymmetric synthesis. For a more in-depth understanding of the mechanism and stereochemical course of this remarkable cleavage reaction, a seven-membered ether analog of such useful biaryl lactones has been investigated structurally, both experimentally, by X-ray diffraction analysis, and by ab initio calculations (B3LYP/6-31G*). In a nearly perfect agreement, both methods show that these seven-membered bridged biaryls do not constitute helicene-like distorted molecules, but ‘true’ biaryls, whose sufficiently long lactone or ether bridge allows the two aromatic systems to adopt a large dihedral angle to each other, without any noticeable deviation from planarity for the two aromatic systems - in contrast to related six-membered analogs, which can rather be considered as helicene-like twisted polycyclic systems.

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