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Chemical Structure| 764-67-0 Chemical Structure| 764-67-0

Structure of 2-Hydroxypalmitic Acid
CAS No.: 764-67-0

Chemical Structure| 764-67-0

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Synonyms: 2-Hydroxyhexadecanoic acid; 2-Hydroxy C16:0 fatty acid

4.5 *For Research Use Only !

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Kowalski, Caitlin H ; Nguyen, Uyen Thy ; Lawhorn, Susannah ; Smith, T Jarrod ; Corrigan, Rebecca M ; Suh, Won Se , et al.

Abstract: Microbiota promote host health by inhibiting pathogen colonization, yet how host-resident fungi or mycobiota contribute to this process remains unclear. The human skin mycobiota is uniquely stable compared with other body sites and dominated by skin-adapted yeasts of the genus Malassezia. We observe that colonization of human skin by Malassezia sympodialis significantly reduces subsequent colonization by the prominent bacterial pathogen Staphylococcus aureus. In vitro, M. sympodialis generates a hydroxyl palmitic acid isomer from environmental sources that has potent bactericidal activity against S. aureus in the context of skin-relevant stressors and is sufficient to impair S. aureus skin colonization. Leveraging experimental evolution to pinpoint mechanisms of S. aureus adaptation in response to antagonism by Malassezia, we identified multiple mutations in the stringent response regulator Rel that promote survival against M. sympodialis and provide a competitive advantage on human skin when M. sympodialis is present. Similar Rel alleles have been reported in S. aureus clinical isolates, and natural Rel variants are sufficient for tolerance to M. sympodialis antagonism. Partial stringent response activation underlies tolerance to clinical antibiotics, with both laboratory-evolved and natural Rel variants conferring multidrug tolerance in a manner that is dependent on the alternative sigma factor SigB. These findings demonstrate the ability of the mycobiota to mediate pathogen colonization resistance through generation of a hydroxy palmitic acid isomer, identify new mechanisms of bacterial adaptation in response to microbiota antagonism, and reveal the potential for microbiota-driven evolution to shape pathogen antibiotic susceptibility.

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Schaum, Andre ; Bates, Kelvin ; Min, Kyung-Eun ; Myers, Faith ; Longnecker, Emmaline ; Canagaratna, Manjula , et al.

Abstract: A method is described for coupling a high-performance liquid chromatograph (HPLC) and chemical ionization mass spectrometer (CIMS) for offline analysis of organic aerosol. It employs a nebulizer interface and an Aerodyne Vaporization Inlet for Aerosols (VIA), allowing for the transmission of analytes from the HPLC eluent into the CIMS inlet. Performance of the HPLC-VIA-CIMS system was assessed through analysis of carboxylic acid standards, environmental chamber-generated secondary organic aerosol (SOA) formed from the ozonolysis of α-pinene, and ambient OA collected at an urban setting. Chromatographic peak shapes were retained through nebulization and evaporation, providing baseline-resolved separation of C6-C18 carboxylic acids and generating molecular-level detail that is not attainable using HPLC or CIMS alone. Instrument response was found to be linear (R2>0.97) over an order of magnitude (0.2–3.0 nmol or 2–30 nmol) for each of the 12 standards. Analysis of α-pinene ozonolysis SOA achieved isomer-resolved detection of both monomer and dimer reaction products and, through the use of a diode array detector (DAD), illustrated the preservation of chromatographic peak shape through nebulization and evaporation. The HPLC-VIA-CIMS instrument also shows potential for quantitative analysis, provided that authentic standards can be purchased or synthesized, and semiquantitative analysis of UV-absorbing compounds such as nitrates and carboxylic acids by using a DAD. The system is compatible with small sample quantities (e.g., 30 μg of α-pinene ozonolysis SOA), allowing for detailed molecular characterization of field-collected SOA, including the identification of several monoterpene oxidation products.

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Product Details of [ 764-67-0 ]

CAS No. :764-67-0
Formula : C16H32O3
M.W : 272.42
SMILES Code : CCCCCCCCCCCCCCC(O)C(O)=O
Synonyms :
2-Hydroxyhexadecanoic acid; 2-Hydroxy C16:0 fatty acid
MDL No. :MFCD00014343

Safety of [ 764-67-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 764-67-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 0
Fraction Csp3 0.94
Num. rotatable bonds 14
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 81.96
TPSA ?

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

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.09
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

6.23
Log Po/w (WLOGP)?

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

4.52
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.

3.31
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

4.52
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.34

Water Solubility

Log S (ESOL):?

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

-4.53
Solubility 0.00804 mg/ml ; 0.0000295 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-7.22
Solubility 0.0000163 mg/ml ; 0.0000000597 mol/l
Class?

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

Poorly soluble
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

-4.38
Solubility 0.0114 mg/ml ; 0.000042 mol/l
Class?

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

Moderately soluble

Pharmacokinetics

GI absorption?

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

High
BBB permeant?

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

Yes
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

Yes
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

Yes
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.

-3.54 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

0.0
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

1.0
Egan?

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

0.0
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

1.0
Bioavailability Score?

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

0.56

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)

2.99

Application In Synthesis of [ 764-67-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 764-67-0 ]
 

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