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Chemical Structure| 819050-89-0

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Hirtzel, Erin ; Edwards, Madison ; Freitas, Dallas ; Liu, Ziying ; Wang, Fen ; Yan, Xin

Abstract: Characterization of nonpolar lipids is crucial due to their essential biol. functions and ability to exist in various isomeric forms. In this study, we introduce the N-H aziridination method to target carbon-carbon double bonds (C=C bonds) in nonpolar sterol lipids. The resulting fragments are readily dissociated upon collision-induced dissociation, generating specific fragment ions for C=C bond position determination and fingerprint fragments for backbone characterization. This method significantly enhances lipid ionization efficiency, thereby improving the sensitivity and accuracy of nonpolar lipid anal. We demonstrated that aziridination of sterols leads to distinctive fragmentation pathways for chain and ring C=C bonds, enabling the identification of sterol isomers such as desmosterol and 7-dehydrocholesterol. Furthermore, aziridination can assist in identifying the sterol backbone by providing fingerprint tandem mass spectra. We also demonstrated the quant. capacity of this approach with a limit of detection of 10 nM in the solvent mixture of methanol and water. To test the feasibility of this method in complex biol. samples, we used mouse prostate cancerous tissues and found significant differences in nonpolar lipid profiles between healthy and cancerous samples. The high efficiency and specificity of aziridination-assisted mass spectrometric anal., as well as its quant. anal. ability, make it highly suitable for broad applications in nonpolar lipid research.

Purchased from AmBeed:

Iram Muzaffar ;

Abstract: Over the years bacteria have developed resistance against antibiotics. Overuse and misuse of antibiotics is one of the main reasons of this increased bacterial resistance. A recently discovered peptide antibiotic known as teixobactin has shown potent activity against Gram-positive bacteria including methicillin-resistant Staphylococcus. aureus (MRSA), Mycobacterium tuberculosis, and vancomycin-resistant enterococci, (VRE). The structure of teixobactin consists of several uncommon amino acids including D-amino-acids and L-allo-enduracididine. L-allo-Enduracididine is a unique amino acid residue consisting of a 5-membered guanidine ring, which offers a great challenge for its synthesis. Most of the reported syntheses of L-allo-enduracididine are lengthy and consist of a lack of stereoselectivity and overall low yields, which stresses the need to develop a more efficient synthetic route to enduracididine using readily available reagents.A synthetic strategy was proposed to construct the 5-membered cyclic guanidine structure using a C-H amination reaction catalyzed by Rh2(esp)2 as the key step. For this purpose, attempts to synthesize various arginine derivatives bearing a 2,2,2-trichloroethoxysulfonyl- (Tces-) protected guanidine were conducted by condensing isothiourea 21 with different derivatives of L-ornithine. First, 2,2,2-trichloroethylsulfamate (24) was synthesized from chlorosulfonyl isocyanate (CSI) with 57% yield. S,S-Dimethyl-N-(2,2,2-trichloroethoxysulfonyl)carbonimidodithionate (25) was made from 24 in 89% yield, which was consequently converted to S-Methyl-N-(2,2,2-trichloroethoxysulfonyl)isothiourea (21) in 94 % yield. Ester derivatives of L-ornithine were synthesized, including N-(δ-tert-butoxycarbonyl)-N-(α-([fluoren-9-yl]methoxy)carbonyl)-L-ornithine methyl ester (28) in 80% yield, and N-(δ-tert-butoxycarbonyl)-N-(α-([fluoren-9-yl]methoxy)carbonyl-L-ornithine allyl ester (34) in 93 % yield. Removal of the Boc protecting group was followed by the attempted coupling of the L-ornithine derivatives with 21, which was unsuccessful and instead gave product whose NMR data was consistent with the formation of a lactam (38) resulting from reaction of the -amino group with the ester. C-H amination was attempted on L-Ornithine, N2-[(9H-fluoren-9-ylmethoxy)carbonyl]-N5-[imino[[(4-methylphenyl)sulfonyl]amino]methyl], methyl ester (41) by using Rh2(esp)2 which gave a complex mixture of compounds. The presented strategy could be used in the future for synthesizing protected arginine derivatives by modifications in the starting molecules. These would serve as substrates for making nitrogen-based heterocyclic compounds via C-H amination by exploring different Rh based catalysts.

Purchased from AmBeed: ; ; ; ; ; 127-19-5

Erin Hirtzel ; Madison Edwards ; Dallas Freitas ; Xin Yan ;

Abstract: Characterization of nonpolar lipids is of significance, as they serve a variety of key biological functions and can naturally exist in isomeric forms. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool for most lipid analysis, but nonpolar lipids do not easily ionize in electrospray, complicating their analyses. In this work, we use the Du Bois catalyst (Rh2(esp)2) for aziridina-tion of carbon-carbon double bonds (C=C bond) of six nonpolar sterol lipids, simultaneously increasing ionization efficiency of nonpolar lipids and facilitating C=C bond identification. The incorporation of nitrogen expands the lipid categories detected by MS, and higher-energy C-trap dissociation of the aziridines generates diagnostic ions that can be used to locate C=C bond positions.

Purchased from AmBeed:

Alternative Products

Product Details of [ 819050-89-0 ]

CAS No. :819050-89-0
Formula : C32H40O8Rh2
M.W : 758.47
SMILES Code : CC(-C1=O-[Rh+2]2(-[O-]-C(-C(C)(C)-C-C3=C-C4=C-C=C-3)=O-5)(-[O-]-C(-C(C)(-C-C6=C-C(-C-C(C)(C)-C7=O-2)=C-C=C-6)C)=O-8)-[Rh+2]58(-[O-]-7)-[O-]-1)(-C-4)C
MDL No. :MFCD08457636

Safety of [ 819050-89-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 819050-89-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 42
Num. arom. heavy atoms 12
Fraction Csp3 0.5
Num. rotatable bonds 0
Num. H-bond acceptors 8.0
Num. H-bond donors 0.0
Molar Refractivity 147.94
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

136.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

7.84
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

5.68
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.89
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.33
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.55

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-9.69
Solubility 0.000000154 mg/ml ; 0.0000000002 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-10.55
Solubility 0.0000000212 mg/ml ; 0.0 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Insoluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-10.59
Solubility 0.0000000193 mg/ml ; 0.0 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Insoluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.36 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

1.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

3.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

7.64
 

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