Direct Assembly of Polysubstituted Furans via C(sp 3 )−H Bond Functionalization by Using Dimethyl Sulfoxide as a Dual Synthon

2019 ◽  
Vol 361 (5) ◽  
pp. 1084-1091 ◽  
Author(s):  
Yufeng Liu ◽  
Yuqun Hu ◽  
Zhongzhong Cao ◽  
Xi Zhan ◽  
Weiping Luo ◽  
...  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Bond Functionalization ◽  
Direct Assembly

The Effect of Dimethyl Sulfoxide on In Vitro Platelet Function

1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Dimethyl Sulfoxide ◽  
Platelet Function ◽  
Platelet Volume ◽  
Short Term ◽  
Platelet Factor ◽  
Short Term Exposure ◽  
Structural Abnormalities

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.

Preservation of Morphological Integrity and Clot Retraction Activity of Human Platelets After Freezing

1964 ◽  
Vol 11 (01) ◽  
pp. 222-229 ◽  
Author(s):  
Isaac Djerassi ◽  
Albert Roy ◽  
Jorge Alvarado ◽  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Liquid Nitrogen ◽  
Human Platelets ◽  
Slow Freezing ◽  
Critical Conditions ◽  
Plasma Medium ◽  
Clot Retraction ◽  
Controlled Freezing ◽  
Direct Immersion

SummaryHuman platelets frozen at −195° C (liquid nitrogen) retain their morphological integrity and ability to promote clot retraction when 5% dimethyl-sulfoxide and 5% dextrose are added to the suspending plasma medium. Slow freezing was more effective than direct immersion in the liquid nitrogen. Although similar results may be achieved with dimethylsulfoxide alone with rigidly controlled freezing rates, the addition of sugars may permit freezing under less critical conditions.Dimethylsulfoxyd und 5% Dextrose dem Plasmamilieu hinzugefügt werden. Das langsame Einfrieren ist effektiver als das direkte Eintauchen in flüssigen Stickstoff. Obschon ähnliche Resultate mit Dimethylsulfoxyd allein unter exakter Kontrolle der Einfrierungsgeschwindig-keit erreicht werden können, erlaubt die Zugabe von Dextrose ein Einfrieren unter weniger kritischen Bedingungen.

Molecular Basis of Iterative C–H Oxidation by TamI, a Multifunctional P450 Monooxygenase from the Tirandamycin Biosynthetic Pathway

2020 ◽  
Author(s):  
Sean A. Newmister ◽  
Kinshuk Raj Srivastava ◽  
Rosa V. Espinoza ◽  
Kersti Caddell Haatveit ◽  
Yogan Khatri ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Basis ◽  
Hydrophobic Interactions ◽  
Cytochromes P450 ◽  
Targeted Mutagenesis ◽  
P450 Monooxygenase ◽  
Bond Functionalization ◽  
Dynamics Simulations

Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM/MM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.<br>

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

2017 ◽  
Author(s):  
Haibo Ge ◽  
Lei Pan ◽  
Piaoping Tang ◽  
Ke Yang ◽  
Mian Wang ◽  
...  
Keyword(s):  
Bond Activation ◽  
Theoretical Calculations ◽  
Experimental Studies ◽  
Bond Functionalization ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Mechanistic Investigation ◽  
Palladium Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

Macrocycles of Higher Ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Macrocycles of Higher ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Connecting Remote C–H Bond Functionalization and Decarboxylative Coupling Using Simple Amines

2019 ◽  
Author(s):  
Francisco de Azambuja ◽  
Ming-Hsiu Yang ◽  
Alexander Bruecker ◽  
Paul Cheong ◽  
Ryan Altman
Keyword(s):  
Organic Molecules ◽  
Mechanistic Studies ◽  
Bond Functionalization ◽  
Bond Forming ◽  
Decarboxylative Coupling

The manuscript describes a Pd-catalyzed reaction of benzylic electrophiles that gives para-substituted arene products. Mechanistic studies suggest a mechanism involving a dearomative C–C bond-forming step, followed by base-mediated rearomatization. This mechanism is uncommon and underappreciated in Pd-catalysis and further exploitation of this mechanism should enable access to other organic molecules.

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