106757-10-2

Basic information

• Product Name: methyl lithocholate
• CAS NO: 106757-10-2
• Molecular Weight: 390.607
• Mol File: 106757-10-2.mol
• Article Data: 86

Chemical Properties

• CAS DataBase Reference: methyl lithocholate(CAS DataBase Reference)
• NIST Chemistry Reference: methyl lithocholate(106757-10-2)
• EPA Substance Registry System: methyl lithocholate(106757-10-2)

Safety Data

• Hazardous Substances Data: 106757-10-2(Hazardous Substances Data)

Upstream product

• 60-29-7 diethyl ether 
• 20231-57-6 methyl 5-cholenoate 
• 64-19-7 acetic acid 
• 64-17-5 ethanol 
• 67-56-1 methanol 
• 5015-59-8 3α-formyloxy-5β-cholan-24-oic acid 
• 4057-84-5 acetyllithocholic acid 
• 434-13-9 Lithocholic acid 
• 74-88-4 methyl iodide 
• 1452-33-1 methyl 3-oxo-4-cholenolate 
• 1173-32-6 methyl 3-oxo-5β-cholan-24-oate 
• 1249-75-8 methyl 3β-hydroxy-5α-cholan-24-oate 
• 84061-62-1 methyl 3β-tosyloxy-5α-cholan-24-oate 
• 19038-19-8 (+)-3-oxo-5α-cholan-24-oic acid 

Downstream Products

• 99598-00-2 para-chloromethylbenzoyloxy-3α cholanate de methyle 
• 107180-35-8 3α-(toluene-4-sulfonyloxy)-5β-cholan-24-oic acid ethyl ester 
• 134878-46-9 Methyl-3α-benzyloxy-5percentb-cholan-24-oate 
• 84061-62-1 methyl 3β-tosyloxy-5α-cholan-24-oate 
• 104538-82-1 C₃₂H₄₆O₄ 
• 1249-75-8 methyl 3α-hydroxy-5α-cholan-24-oate 
• 75239-91-7 lithocholic acid O-β-D-glucuronide 
• 3253-69-8 methyl 3α-acetoxy-5β-cholan-24-oate 

Relevant articles and documents

Synthesis and anticancer activity of hybrid molecules based on lithocholic and (5Z,9Z)-tetradeca-5,9-dienedioic acids linked via mono(di,tri,tetra)ethylene glycol and α,ω-diaminoalkane units

For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)- 1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2-4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.

Synthesis of spiroannulated oligopyrrole macrocycles derived from lithocholic acid

Two new steroidal spiroannulated calix[4]pyrroles 5 and 10, derived from bile acids (lithocholate), were prepared by the acid catalyzed condensation of methyl-3,3-bis(pyrrol-2-yl)-5β-cholan-24-oate 3 with carbonyl compounds and with 2,2′-propane-2,2-diylbis(1H-pyrrole), respectively. The new compounds were fully characterized by physicochemical methods.

Deciphering the role of charge, hydration, and hydrophobicity for cytotoxic activities and membrane interactions of bile acid based facial amphiphiles

We synthesized four cationic bile acid based facial amphiphiles featuring trimethyl ammonium head groups. We evaluated the role of these amphiphiles for cytotoxic activities against colon cancer cells and their membrane interactions by varying charge, hydration and hydrophobicity. The singly charged cationic Lithocholic acid based amphiphile (LCA-TMA1) is most cytotoxic, whereas the triply charged cationic Cholic acid based amphiphile (CA-TMA 3) is least cytotoxic. Light microscopy and Annexin-FITC assay revealed that these facial amphiphiles caused late apoptosis. In addition, we studied the interactions of these amphiphiles with model membrane systems by Prodan-based hydration, DPH-based anisotropy, and differential scanning calorimetry. LCA-TMA1 is most hydrophobic with a hard charge causing efficient dehydration and maximum perturbations of membranes thereby facilitating translocation and high cytotoxicity against colon cancer cells. In contrast, the highly hydrated and multiple charged CA-TMA3 caused least membrane perturbations leading to low translocation and less cytotoxicity. As expected, Chenodeoxycholic acid and Deoxycholic acid based amphiphiles (CDCA-TMA2, DCA-TMA2) featuring two charged head groups showed intermediate behavior. Thus, we deciphered that charge, hydration, and hydrophobicity of these amphiphiles govern membrane interactions, translocation, and resulting cytoxicity against colon cancer cells.

Bile acid amphiphiles with tunable head groups as highly selective antitubercular agents

Tuberculosis faces major challenges for its cure due to (a) long treatment period, (b) emergence of drug resistance bacteria, and (c) poor patient compliance. Disrupting the membrane integrity of mycobacteria as a therapeutic strategy has not been explored well as the rigid, waxy, and hydrophobic nature of mycobacterial lipids does not allow binding and penetration of charged amtimicrobial amphiphiles and peptides. Here, we present a new concept that fine-tuning of the charged head group modulates the specificity of amphiphiles against bacterial membranes. We show that hard-charged amphiphiles interact with mycobacterial trehalose dimycolates and penetrate through rigid mycobacterial membranes. In contrast, soft-charged amphiphiles specifically inhibit the growth of both E. coli and S. aureus via electrostatic interactions. These subtle variations between interactions of amphiphiles and bacterial membranes could be explored further to design more specific and potent antimycobacterial agents. This journal is

Development of novel lithocholic acid derivatives as vitamin D receptor agonists

Lithocholic acid (2) was identified as the second endogenous ligand of vitamin D receptor (VDR), though its binding affinity to VDR and its vitamin D activity are very weak compared to those of the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1). 3-Acylated lithocholic acids were reported to be slightly more potent than lithocholic acid (2) as VDR agonists. Here, aiming to develop more potent lithocholic acid derivatives, we synthesized several derivatives bearing a 3-sulfonate/carbonate or 3-amino/amide substituent, and examined their differentiation-inducing activity toward human promyelocytic leukemia HL-60 cells. Introduction of a nitrogen atom at the 3-position of lithocholic acid (2) decreased the activity, but compound 6 bearing a 3-methylsulfonate group showed more potent activity than lithocholic acid (2) or its acylated derivatives. The binding of 6 to VDR was confirmed by competitive binding assay and X-ray crystallographic analysis of the complex of VDR ligand-binding domain (LBD) with 6.

Synthesis and characterization of novel bile-acid - heteroaryl conjugates with N-(2-aminoethyl)amido linker

Four novel bile acid conjugates N-[2-([2,2′]-bithiophen-5-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (1), N-[2-([2,2′]-bithiophen-5-ylmethyl)aminoethyl]-3α,7α,12α-trihydroxy-5β-cholan-24-amide (2), N-[2-(1H-pyrrol-2-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (3), N-[2-(pyridin-2-ylmethyl)aminoethyl]-3α-hydroxy-5β-cholan-24-amide (4) have been synthesized in moderate to good yields, and their structures have been characterized by 1H, 13C, 13C DEPT-135, PFG 1H,13C HMQC, and PFG 1H,13C HMBC NMR spectra. Their molecular weights and elemental compositions have been determined by ESI-TOF mass spectrometry and elemental analyses. Crystal structure of 1 characterized with orthorhombic P212121 space group has also been determined.

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Synthesis of new cisplatin derivatives from bile acids

A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in vitro and some hybrid molecules showed an expected activity.

Dimerization of lithocholate unsaturated esters using the 'second generation' Grubbs' reagent

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Diversity oriented one-pot synthesis of complex macrocycles: Very large steroid-peptoid hybrids from multiple multicomponent reactions including bifunctional building blocks

Sixteen in one go: Up to 16 new bonds connect 12 building blocks to form 54-membered macrocycles (46-membered example shown) in a one-pot procedure combining bifunctional components with multicomponent reactions. The large rings are not made of repetitive subunits and form an ideal basis for the fast construction of libraries of chiral host molecules. (Chemical Equation Presented)

Lithocholic acid derivative in the presence of dimethyl sulfoxide: Morphology and phase transitions

We report on the properties of a new organogelator, which is an ether derivative of lithocholic acid (7OPhOLCA). The correctness of the chemical structure and purity of 7OPhOLCA was confirmed by thin layer chromatography, proton nuclear magnetic resonance (1H NMR) spectroscopy, elemental analysis (EA) and infrared spectroscopy (IR). Phase transition temperatures and enthalpies of the gel were obtained by differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). Changes in the vibrational spectra depending on the temperature modifications were studied using the technique of FTIR Spectroscopy with 2D correlation analysis. The small angle neutron scattering method (SANS) was used to determine the morphology and internal structure of the investigated system. It was found that the substance forms a non-transparent stable gel with a spherulite organization at the macro-scale level. The morphology of the self-assemblies and internal structure at the nano-scale level are quite different with variation of the temperature in the Gel phase. A further increase in temperature leads to the formation of the sol phase again. It turns out that the temperature of the gel-sol transition changes significantly with the concentration of 7OPhOLCA. The results of the DSC and SANS measurements indicated the reversible behavior of the Gel-SolGel transition with hysteresis on the temperature during heating and cooling.

First synthesis of steroidal 1,2,4-trioxolanes

Griesbaum ozonolysis of mixtures of methyl 3-(methoxyimino)-5β-cholan- 24-oate with ketones (cyclohexanone, methyl trifluoromethyl ketone, and phenyl trifluoromethyl ketone) afforded for the first time steroidal 1,2,4-trioxolanes which were isolated as mixtures of stereoisomers.

Facile synthesis of 5β-cholane-sym-triazine conjugates starting from metformin and bile acid methyl esters: Liquid and solid state NMR characterization and single crystal structure of lithocholyl triazine

Four bile acid-triazine conjugates: N2′,N2′-dimethyl-6′-(3α-hydroxy-5β-24-norcholyl)-1′,3′,5′-triazine-2′,4′-diamine (lithocholyl triazine, 4a), N2′,N2′-dimethyl-6′-(3α,7α-dihydroxy-5β-24-norcholyl)-1′,3′,5′-triazine-2′,4′-diamine (chenodeoxycholyl triazine, 4b), N2′,N2′-dimethyl-6′6′-(3α,12α-dihydroxy-5β-24-norcholyl)-1′,3′,5′-triazine-2′,4′-diamine (deoxycholyl triazine) (4c), and N2′,N2′-dimethyl-6′-(3α,7α,12α-trihydroxy-5β-24-norcholyl)-1′,3′,5′-triazine-2′,4′-diamine (cholyl triazine) (4d) have been prepared and characterized by liquid and solid state NMR. An improved synthetic method produced better yields and an easier purification procedure for 4d than reported in the literature. Single crystal structure of 4a is reported: empirical formula C28H47N5O, monoclinic P21 space group with unit cell dimensions, a 18.7135(5) A?, b 7.4510(2) A?, c 19.3073(5) A?, β 95.7290(10)°, volume 2678.65(12) A?3.

Deoxygenative Borylation of Secondary and Tertiary Alcohols

Two different approaches for the deoxygenative radical borylation of secondary and tertiary alcohols are presented. These transformations either proceed through a metal-free silyl-radical-mediated pathway or utilize visible-light photoredox catalysis. Readily available xanthates or methyl oxalates are used as radical precursors. The reactions show broad substrate scope and high functional-group tolerance, and are conducted under mild and practical conditions.

Synthesis of steroid-porphyrin conjugates from oestradiol, oestrone, and lithocholic acid

The synthesis of porphyrin-steroid conjugates is examined using the natural steroids oestradiol, oestrone, and lithocholic acid as precursors. Two strategies differing in the timing of formation of the steroid-porphyrin linkage leading to four different construction motifs are explored. Two approaches are based on a strategy of introduction of steroidal components in the porphyrin-forming reaction involving condensation of steroidal-alkylaldehydes and pyrrole to give 5,10,15,20-tetrakis(steroidal-alkyl)porphyrins and differ in the way in which the required aldehyde is introduced to the steroidal component. In the other strategy, a steroidal component is introduced by post-porphyrin synthesis reactions and here also two approaches were explored, one involving nucleophilic substitution and the other esterification. Of the four approaches investigated, the most efficient and most versatile one attaches the steroidal components late in the sequence to a 5,10,15,20-tetra(ω-haloalkyl)porphyrin by a nucleophilic substitution reaction. In this way, a 5,10,15,20-tetrakis [oestrone-linked-heptyl)porphyrin was obtained in 47% yield.

Anchoring cationic amphiphiles for nucleotide delivery significance of DNA release from cationic liposomes for transfection

We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.

Comparison of epimeric methyl lithocholate and methyl iso-lithocholate molecules: Single crystal X-ray structure of methyl lithocholate, ab initio HF/6-31G* optimized structures and experimental and calculated DFT/B3LYP 13C NMR chemical shifts

13C NMR chemical shifts have been measured and assigned for epimeric methyl 3α/β-hydroxy-5β-cholan-24-oates (methyl lithocholate [3α-OH epimer] and methyl iso-lithocholate [3β-OH epimer]). Their molecular dynamics simulations suggest that for both epimers there exists two predominant gas phase conformations, which have been further forwarded for ab initio/HF optimizations and DFT/GIAO based 13C NMR chemical shift calculations. Excellent linear relationships have been observed between experimental and calculated 13C NMR chemical shifts for both epimers. For methyl lithocholate (MeLC), the other minimum energy conformation equates very well with the single crystal X-ray structure (orthorhombic, space group P212121, unit cell a = 7.14710(10) A?, b = 11.9912(2) A?, c = 26.4368(5) A?). The crystalline packing of MeLC consists of continuous parallel intermolecular hydrogen bonded [3α-OH···O=C24] head-to-tail polymeric chains, which are further cross-linked by many simultaneous weak C(sp3)H···O-type of interactions.

Highly Chemoselective Deprotection of the 2,2,2-Trichloroethoxycarbonyl (Troc) Protecting Group

Nonreducing, pH-neutral conditions for the selective cleavage of the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group are reported. Using trimethyltin hydroxide in 1,2-dichloroethane, Troc-protected alcohols, thiols, and amines can be selectively unmasked in the presence of various functionalities that are incompatible with the reducing conditions traditionally used to remove the Troc group. This mild deprotection protocol tolerates a variety of other hydrolytically sensitive and acid/base-sensitive moieties as well.

Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite

In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.

Membrane transport inspired hydrolysis of non-activated esters at near physiological pH

A positively charged micelle loaded with substrates was transported selectively to the reaction site (cathode) to promote the proximity and localization of the reactants (ester and hydroxide). The guided vehicular delivery coupled with electrolysis allows the hydrolysis of non-activated esters at near physiological pH with significant yields along with recyclability.