Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non‐UV‐Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method

Abstract

Property tuning by fluorination is very effective for an umber of purposes,a nd currently increasingly investigated for aliphatic compounds.A ni mportant application is lipophilicity (log P) modulation. However,t he determination of log Pi sc umbersome for non-UV-active compounds.Anew variation of the shake-flask log Pd etermination method is presented, enabling the measurement of log Pf or fluorinated compounds with or without UV activity regardless of whether they are hydrophilic or lipophilic. No calibration curves or measurements of compound masses/aliquot volumes are required. With this method, the influence of fluorination on the lipophilicity of fluorinated aliphatic alcohols was determined, and the log Pvalues of fluorinated carbohydrates were measured. Interesting trends and changes,for example,for the dependence on relative stereochemistry,are reported.

Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole‐2‐carboxylic acid

“…Interestingly, the lipophilicity difference between the N‐pivaloylated peptide PivP6F2 and the N‐acetylated one AcP6F2 was identical as in the small molecule models (entry 2 vs 1 in Table ). The oligo‐Oic peptides were remarkably lipophilic, having log P values increasing with the oligomeric number, and this value reached the method detection limits (this is 3 < log P ) already at the oligomeric number 3 and higher.…”

“…Thus, we determined the experimental octan‐1‐ol/water partitioning constants for derivatives of several amino acids (Scheme ). Accurate partitioning values can be measured by NMR, and few elegant methods have been developed quite recently . We measured log P values for a few amino acid derivatives as shown in Figure .…”

“…Accurate partitioning values can be measured by NMR, and few elegant methods have been developed quite recently. [47][48][49][50] We measured logP values for a few amino acid derivatives as shown in Figure 2. The analysis demonstrated that proline has a relatively polar structure (approximately as polar as alanine), whereas Oic is relatively nonpolar, with a higher hydrophobicity than the examined canonical hydrophobic amino acids (Val, Ile, Leu, and Phe).…”

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

“…Not only does the high CÀFb ond energy render it resistant to in vivo degradation, but the fluoro substituent can increase lipophilicity, which in turn can increase cell permeability. [41] Finally, in the context of this study,alimitation of our library is the low water solubility of polyfluorinated analogues, especially for compounds with the b-S-(2-naphthyl)a glycone, and the low affinity between fluorine atoms and the calcium cation. One can assume that members of our library of fluorinated analogues would be more suitable as ligandsf or other galactophilic proteins thatd on ot include ac ationic metal center in the carbohydrate recognition domain.…”

Selective S‐Deacetylation of Functionalized Thioacetates Catalyzed by Dy(OTf)3

“…The title compound was prepared from compound A [37] (1. S-(5-((tert-Butoxycarbonyl)oxy)pentyl) Ethanethioate (4) 1,5-Pentanediol (1.43 g, 13.75 mmol, 3equiv), pyridine (5.5 mL), DMAP (56 mg, 0.46 mmol, 0.1 equiv), and di-tert-butyl dicarbonate (1.05 mL, 4.58 mmol, 1equiv) were stirred in ar ound-bottomed flask at RT until the starting material had been completely consumed and then the mixture was quenched with water and extracted with EtOAc.…”