The Palladium-Mediated Cross Coupling of Bromotropolones With Organostannanes or Arylboronic Acids: Applications to the Synthesis of Natural Products and Natural Product Analogs

1991 ◽  
Vol 44 (5) ◽  
pp. 705 ◽  
Author(s):  
MG Banwell ◽  
JM Cameron ◽  
MP Collis ◽  
GT Crisp ◽  
RW Gable ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Natural Products ◽  
Natural Product ◽  
Cross Coupling ◽  
Binding Activity ◽  
X Ray ◽  
Arylboronic Acids ◽  
Wide Range ◽  
Tubulin Binding

The bromotropolones (4), (5) and (10) undergo palladium-mediated cross coupling with a wide range of organostannanes to produce alkenyl -, alkyl- and aryl-substituted tropolones . The methodology has been applied to the synthesis of the monoterpenes β- dolabrin (11),β- thujaplicin (12), 4-isopropyl-7-methoxytropolone (13) and β- thujaplicinol (14). Cross coupling of bromotropolones (4), (5) and (10) with various aryltrimethylstannanes or arylboronic acids has permitted the preparation of the bicyclic colchicine analogues (30)-(43) which have been tested for tubulin -binding activity. The X-ray crystal structure of the most active of these systems, compound (38), is reported.

scholarly journals Preparation of pyridine-3,4-diols, their crystal packing and their use as precursors for palladium-catalyzed cross-coupling reactions

2010 ◽  
Vol 6 ◽  
Author(s):  
Tilman Lechel ◽  
Irene Brüdgam ◽  
Hans-Ulrich Reissig
Keyword(s):  
Crystal Structure ◽  
Crystal Packing ◽  
Cross Coupling ◽  
Crystal Structure Analysis ◽  
Coupling Reactions ◽  
X Ray ◽  
Cross Coupling Reactions ◽  
Fluorescence Measurements ◽  
Subsequent Conversion ◽  
Palladium Catalyzed

A series of trifluoromethyl-substituted 3-alkoxypyridinol derivatives has been deprotected to furnish pyridine-3,4-diol derivatives in good yields. The X-ray crystal structure analysis proved that a 1:1 mixture of pyridine-3,4-diols and their pyridin-4-one tautomers exist in the solid state. Subsequent conversion into bis(perfluoroalkanesulfonate)s were smoothly achieved. The obtained compounds were used as substrates for palladium-catalyzed coupling reactions. Fluorescence measurements of the biscoupled products showed a maximum of emission in the violet region of the spectrum.

Synthesis, X-Ray Crystal Structure and Tubulin- Binding Properties of a Benzofuran Analogue of the Potent Cytotoxic Agent Combretastatin A4

1999 ◽  
Vol 52 (8) ◽  
pp. 767 ◽  
Author(s):  
Martin G. Banwell ◽  
Bernard L. Flynn ◽  
Ernest Hamel ◽  
Anthony C. Willis
Keyword(s):  
Crystal Structure ◽  
Cytotoxic Agent ◽  
Binding Agent ◽  
Binding Properties ◽  
Antimitotic Agent ◽  
X Ray ◽  
Combretastatin A4 ◽  
Tubulin Binding

The benzofuran (4), a ring-fused analogue of the potent antimitotic agent combretastatin A4 (1), has been prepared by a convergent route involving 5-endo-dig iodocyclization of o-hydroxytolan (5) as the key step. Compound (4), which has been characterized crystallographically as well as spectroscopically, is inactive as a tubulin-binding agent.

Synthesis of the Troponoid Natural Product Nezukone Via Sequential Rearrangement of Two Isomeric Precursors

1993 ◽  
Vol 46 (12) ◽  
pp. 1941 ◽  
Author(s):  
MG Banwell ◽  
CJ Cowden ◽  
GL Gravatt ◽  
CEF Rickard
Keyword(s):  
Crystal Structure ◽  
Natural Product ◽  
X Ray ◽  
Key Features

Nezukone (1) has been synthesized in seven steps from the readily available Δ3-trinorcarene (4). Key features of the sequence used include formation of the bicyclic isomer (2) of compound (1). Base-promoted isomerization of compound (2) followed by acidic workup then produced the isolable but highly unstable heptafulvenol (3), an extended enolic tautomer of nezukone (1). Under mildly basic conditions compound (3) rearranged to give the natural product (1). The X-ray crystal structure of the ring-fused cyclobutanone (8) is reported.

scholarly journals NovelFeIIandCoIIComplexes of Natural Product Tryptanthrin: Synthesis and Binding with G-Quadruplex DNA

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yi-ning Zhong ◽  
Yan Zhang ◽  
Yun-qiong Gu ◽  
Shi-yun Wu ◽  
Wen-ying Shen ◽  
...  
Keyword(s):  
Natural Products ◽  
Ligand Binding ◽  
Single Crystal ◽  
Natural Product ◽  
Significant Interaction ◽  
Rational Design ◽  
X Ray Diffraction ◽  
Quadruplex Dna ◽  
X Ray ◽  
G Quadruplex

Tryptanthrin is one of the most important members of indoloquinoline alkaloids. We obtained this alkaloid fromIsatis. Two novelFeIIandCoIIcomplexes of tryptanthrin were first synthesized. Single-crystal X-ray diffraction analyses show that these complexes display distorted four-coordinated tetrahedron geometry via two heterocyclic nitrogen and oxygen atoms from tryptanthrin ligand. Binding with G-quadruplex DNA properties revealed that both complexes were found to exhibit significant interaction with G-quadruplex DNA. This study may potentially serve as the basis of future rational design of metal-based drugs from natural products that target the G-quadruplex DNA.

The Stereochemistry of Organometallic Compounds. LX. Rhodium-Catalyzed Reactions of Hydrogen and Carbon Monoxide With Alkenylanilines

1994 ◽  
Vol 47 (6) ◽  
pp. 1043 ◽  
Author(s):  
D Anastasiou ◽  
EM Campi ◽  
H Chaouk ◽  
GD Fallon ◽  
WR Jackson ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Carbon Monoxide ◽  
Single Crystal ◽  
Structure Determination ◽  
Cross Coupling ◽  
Organometallic Compounds ◽  
Single Crystal Structure ◽  
Crystal Structure Determination ◽  
X Ray ◽  
Catalyzed Reactions

Rhodium- catalysed reactions of o- or p- cyano-N-allylanilines with H2/CO give N- arylpyrrolidine aldehydes resulting from a double hydroformylation sequence. In contrast reactions of o- or p-methyl-N-allylanilines or N- allylaniline itself with H2/CO give ' dimeric ' compounds resulting from self-condensation reactions of an initially formed hydroformylation product together with varying amounts of the double hydroformylation product. Similar reactions of o-cyano-N-but-3-enylanilines give low yields of double hydroformylation products and major products arising from hydrogenation or cross coupling of intermediate enamines. The structure of one of these products, N-2-cyanophenyl-5-(N′-2-cyanophenyl-3-methyl-pyrrolidin-2-yl)-1,2,3,4-tetrahydropyridine (17) (IUPAC name: 2-[5-{1-(2-cyanophenyl)-3-methylpyrrolidin-2-yl}-1,2,3,4-tetrahydropyridin-1-yl] benzonitrile ) was confirmed by an X-ray single-crystal structure determination.

Single Crystal X-Ray Structural Determination: A Powerful Technique for Natural Products Research and Drug Discovery

2012 ◽  
Vol 545 ◽  
pp. 3-15
Author(s):  
Hoong Kun Fun ◽  
Suchada Chantrapromma ◽  
Nawong Boonnak
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Single Crystal ◽  
Natural Product ◽  
Structure Determination ◽  
Three Dimensional ◽  
X Ray ◽  
Powerful Technique ◽  
Determination Of Absolute Configuration

Drug discovery from natural products resources have been extensively studied. The most important step in the discovery process is the identification of compounds with interesting biological activity. Single crystal X-ray structure determination is a powerful technique for natural products research and drug discovery in which the detailed three-dimensional structures that emerge can be co-related to the activities of these structures. This article shall present (i) co-crystal structures, (ii) determination of absolute configuration and (iii) the ability to distinguish between whether a natural product compound is a natural product or a natural product artifact. All these three properties are unique to the technique of single crystal X-ray structure determination.

scholarly journals Crystal structure of 5-[(benzoyloxy)methyl]-5,6-dihydroxy-4-oxocyclohex-2-en-1-yl benzoate

2020 ◽  
Vol 76 (7) ◽  
pp. 1096-1100
Author(s):  
Theerachart Leepasert ◽  
Patchreenart Saparpakorn ◽  
Kittipong Chainok ◽  
Tanwawan Duangthongyou
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Single Crystal ◽  
Natural Product ◽  
Dihedral Angle ◽  
Absolute Configuration ◽  
Hydroxyl Groups ◽  
X Ray Diffraction ◽  
X Ray ◽  
Ring Form

The crystal structure of the natural product zeylenone, C21H18O7, was confirmed by single-crystal X-ray diffraction. The crystal structure has three chiral centers at positions C1, C5 and C6 of the cyclohexanone ring, but the absolute configuration could not be determined reliably. The methyl benzoate and benzoyloxy substituents at positions C1 and C5 of the cyclohexenone ring are on the same side of the ring with the dihedral angle between their mean planes being 16.25 (10)°. These rings are almost perpendicular to the cyclohexenone ring. The benzoate groups and two hydroxyl groups on the cyclohexenone ring form strong hydrogen bonds to consolidate the crystal structure. In addition, weak C—H...O hydrogen bonds also contribute to the packing of the structure.

The Bradshaw/Bonjoch Synthesis of (-)-Anominine

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Aldol Condensation ◽  
Selective Reduction ◽  
Cross Coupling ◽  
Conjugate Addition ◽  
Quaternary Centers ◽  
Selective Protection ◽  
Open Face ◽  
Robinson Annulation

The Hajos-Parrish cyclization was a landmark in the asymmetric construction of polycarbocyclic natural products. Impressive at the time, the proline-mediated intramolecular aldol condensation proceeded with an ee that was low by modern standards. Ben Bradshaw and Josep Bonjoch of the Universitat de Barcelona optimized this protocol, then used it to prepare (J. Am. Chem. Soc. 2010, 132, 5966) the enone 3 en route to the Aspergillus alkaloid (-)-anominine 4. The optimized catalyst for the enantioselective Robinson annulation was the amide 5 . With 2.5 mol % of the catalyst, the reaction proceeded in 97% ee. With only 1 mol % of catalyst, the reaction could be taken to 96% yield while maintaining the ee at 94%. Conjugate addition proceeded across the open face of 3 to give, after selective protection, the monoketal 7. After methylenation and deprotection, oxidation with IBX delivered the enone 9. With the angular quaternary centers of the natural product in place, the molecule became increasingly congested. Attempted direct alkylation of 9 led mainly to O-methylation. A solution to this problem was found in condensation with the Eschenmoser salt, followed by N-oxide formation and elimination to give the tetraene 10. Selective reduction by the Ganem protocol followed by equilibration completed the net methylation. Under anhydrous conditions, the oxide derived from the allylic selenide 12 did not rearrange. On the addition of water, the rearrangement proceeded smoothly. Protection and hydroboration converted 13 into 14. The bulk of the folded molecule protected the exo methylene of 14, so hydrogenation followed by protection and oxidation delivered 15. Conjugate addition of indole to 15 set the stage for oxidation and bis-methylenation to give 17. Selective Ru-mediated cross-coupling with 18 followed by deprotection then completed the synthesis of (-)-anominine 4, which proved to be the enantiomer of the natural product.

scholarly journals Crescerin uses a TOG domain array to regulate microtubules in the primary cilium

2015 ◽  
Vol 26 (23) ◽  
pp. 4248-4264 ◽  
Author(s):  
Alakananda Das ◽  
Daniel J. Dickinson ◽  
Cameron C. Wood ◽  
Bob Goldstein ◽  
Kevin C. Slep
Keyword(s):  
Crystal Structure ◽  
Binding Activity ◽  
Structure And Function ◽  
Sensory Disorders ◽  
Tubulin Binding ◽  
Sensory Cilia ◽  
And Function ◽  
Binding Determinants ◽  
Extracellular Environment

Eukaryotic cilia are cell-surface projections critical for sensing the extracellular environment. Defects in cilia structure and function result in a broad range of developmental and sensory disorders. However, mechanisms that regulate the microtubule (MT)-based scaffold forming the cilia core are poorly understood. TOG domain array–containing proteins ch-TOG and CLASP are key regulators of cytoplasmic MTs. Whether TOG array proteins also regulate ciliary MTs is unknown. Here we identify the conserved Crescerin protein family as a cilia-specific, TOG array-containing MT regulator. We present the crystal structure of mammalian Crescerin1 TOG2, revealing a canonical TOG fold with conserved tubulin-binding determinants. Crescerin1's TOG domains possess inherent MT-binding activity and promote MT polymerization in vitro. Using Cas9-triggered homologous recombination in Caenorhabditis elegans, we demonstrate that the worm Crescerin family member CHE-12 requires TOG domain–dependent tubulin-binding activity for sensory cilia development. Thus, Crescerin expands the TOG domain array–based MT regulatory paradigm beyond ch-TOG and CLASP, representing a distinct regulator of cilia structure.

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