Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs.

@article{Lee2015TotalSO,
  title={Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs.},
  author={Kiyoun Lee and Yam B. Poudel and Christopher M. Glinkerman and Dale L. Boger},
  journal={Tetrahedron},
  year={2015},
  volume={71 35},
  pages={
          5897-5905
        }
}
The total syntheses of dihydrolysergic acid and dihydrolysergol are detailed based on a Pd(0)-catalyzed intramolecular Larock indole cyclization for the preparation of the embedded tricyclic indole (ABC ring system) and a subsequent powerful inverse electron demand Diels-Alder reaction of 5-carbomethoxy-1,2,3-triazine with a ketone-derived enamine for the introduction of a functionalized pyridine, serving as the precursor for a remarkably diastereoselective reduction to the N-methylpiperidine D… Expand
18 Citations
Intramolecular Fischer Indole Synthesis for the Direct Synthesis of 3,4-Fused Tricyclic Indole and Application to the Total Synthesis of (-)-Aurantioclavine.
TLDR
The preparative utility of this conceptually new synthetic approach, which does not require prefunctionalization of the indole ring, was demonstrated by its application to a concise total synthesis of (-)-aurantioclavine. Expand
Total Synthesis and Stereochemical Assignment of Streptide.
TLDR
It is reported the first total synthesis of streptide that confirms the regiochemistry of the lysine-tryptophan crosslink and provides an unambiguous assignment of the stereochemistry (3R vs 3S) of theLysinesine-2 C3 center. Expand
Total Syntheses of (-)-Hibiscone C and Lysergine: A Cyclization/Fragmentation Strategy.
TLDR
The first asymmetric total synthesis of (-)-hibiscone C and a concise synthesis of ergot alkaloid lysergine are described, achieved using the radical cyclization/fragmentation strategy. Expand
Total Syntheses of Festuclavine, Pyroclavine, Costaclavine, epi-Costaclavine, Pibocin A, 9-Deacetoxyfumigaclavine C, Fumigaclavine G, and Dihydrosetoclavine.
TLDR
The main feature of the synthesis is the use of an unprecedented Pd-catalyzed intramolecular Larock indole annulation/Tsuji-Trost allylation cascade to assemble the tetracyclic core in one step. Expand
Regioselective Direct C-4 Functionalization of Indole: Total Syntheses of (-)-Agroclavine and (-)-Elymoclavine.
An efficient rhodium-catalyzed method for direct C-H functionalization at the C4 position of unprotected indoles has been developed. The utility of this method is demonstrated by the concise totalExpand
Enantioselective Total Synthesis of (+)-Lysergol: A Formal anti-Carbopalladation/Heck Cascade as the Key Step.
The enantioselective synthesis of (+)-lysergol was completed in 12 steps and an overall yield of 13% starting from a known literature precursor. The key step relies on a domino reaction containing aExpand
Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.
TLDR
Hydrogen bonding of non-nucleophilic perfluoroalcohols, including hexafluoroisopropanol and trifluoroethanol, is used to activate the electron-deficient heterocyclic azadienes in cycloaddition of 1,2,3-triazine 4 with enamine 3 as the key step of a concise total synthesis of methoxatin. Expand
Recent applications of the hetero Diels–Alder reaction in the total synthesis of natural products
The synthetic utility and potential power of the Diels–Alder (D–A) reaction in organic chemistry is evident. These significances have been extended to the synthesis of a plethora and wide variety ofExpand
Synthesis, Characterization, and Rapid Cycloadditions of 5-Nitro-1,2,3-triazine.
TLDR
The synthesis, characterization, and a study of the cycloaddition reactions of 5-nitro-1,2,3-triazine are reported, revealing a remarkable reaction rate and efficiency. Expand
Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity.
An efficient synthesis of ergot alkaloid lysergol and its analogues is described, providing compounds for functional evaluation at the human 5-HT1A, 5-HT2A, 5-HT2B, or 5-HT2C receptors. Key featuresExpand
...
1
2
...

References

SHOWING 1-10 OF 82 REFERENCES
Tandem radical cyclisations : Synthesis of lysergic acid derivatives
Abstract A novel free radical cyclisation approach for the synthesis of lysergic acid analogues has been investigated. The homolytic cleavage of carbon-bromine bond, mediated by tri-n-butyltinExpand
Formal total synthesis of (+)-lysergic acid via zinc(II)-mediated regioselective ring-opening reduction of 2-alkynyl-3-indolyloxirane.
TLDR
Asymmetric formal synthesis of (+)-lysergic acid was achieved with a reductive ring-opening reaction of chiral 2-alkynyl-3-indolyloxirane with NaBH(3)CN as the key step to construct the ergot alkaloid core structure. Expand
Total synthesis of (+)-lysergic acid.
We report the enantioselective total synthesis of (+)-lysergic acid using two different strategies, which featured three metal-catalyzed reactions for the construction of the BCD three rings,Expand
Asymmetric total synthesis of ent-(-)-roseophilin: assignment of absolute configuration.
  • D. Boger, J. Hong
  • Chemistry, Medicine
  • Journal of the American Chemical Society
  • 2001
TLDR
Surprisingly, ent-(-)-1 was found to be 2-10-fold more potent than natural (+)-1 in cytotoxic assays, providing an unusually rewarding culmination to synthetic efforts that provided the unnatural enantiomer. Expand
Total synthesis of ningalin D.
A concise (nine-step) and effective (19% overall yield) total synthesis of ningalin D (1a) is disclosed and is based on a key 1,2,4,5-tetrazine --> 1,2-diazine --> pyrrole Diels-Alder strategy toExpand
Benz[cd]indoles. Part III. A New Stereospecific Synthesis of Dihydrolysergic Acid and an Entry to 14‐Substituted Derivatives
A new convenient synthesis of dihydrolysergic acid is described, which allows the preparation of substituted derivatives, especially those with different substitutents in the aromatic ring. StartingExpand
Total synthesis of (+/-)-lysergic acid, lysergol, and isolysergol by palladium-catalyzed domino cyclization of amino allenes bearing a bromoindolyl group.
TLDR
This work investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes with biscyclization as the key step, and total synthesis of (+/-)-lysergic acid, (+/--ly Sergol, and (-/-)-isolysergol was achieved. Expand
The quest for new mild and selective modifications of natural structures: laccase-catalysed oxidation of ergot alkaloids leads to unexpected stereoselective C-4 hydroxylation.
TLDR
Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 2-7, and allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton. Expand
Total Syntheses of (−)-Pyrimidoblamic Acid and P-3A
TLDR
The examination of the key cycloaddition reaction revealed that the inherent 1,2,3-triazine mode of cycloadDition as well as the amidine regioselectivity were unaffected by introduction of two electron-withdrawing groups (−CO2R) even if C5 is unsubstituted (Me or H), highlighting the synthetic potential of the powerful pyrimidine synthesis. Expand
Synthesis of ergot alkaloids from tryptophan
The first total syntheses of lysergine and setoclavine are described, as well as a new and efficient synthesis of lysergic acid. The starting material for these syntheses is tryptophan, protected asExpand
...
1
2
3
4
5
...