629-80-1Relevant articles and documents
From T-antigen to plasmalogen-derived aldehydes: The identification of a marker of colorectal cancer in human rectal mucous
Krepinsky, Jiri J.,Kandel, Gabor P.,Yeung, Ka Sing,Chociej, Jacek,Chen, Min,Cohen, Gideon,Douglas, Stephen P.,Furrer, Rudolf,Kukreti, Vishal,Lupescu, Niculina,Richens, Enoka,Tanner, Keith L.
, p. 109 - 117 (2003)
Recently, a simple noninvasive screening test for colorectal cancer was proposed, based on a hypothesis involving galactose-containing carbohydrate moieties such as the Thomsen-Friedenreich antigen. According to the hypothesis, such carbohydrate moieties, present in the human rectal mucous of patients with colorectal cancer, can be specifically oxidized with galactose oxidase to form substances that, upon reaction with Schiff reagent, yield purple (magenta) coloured compounds. While evaluating this proposed test, we discovered that the colour formation is not due to the proposed reaction between oxidized galactose moieties present in rectal mucous and Schiff reagent. We found instead that the mucous from colorectal cancer patients contains compounds that form purple (magenta) adducts with the Schiff reagent directly, i.e., they do not require oxidation by galactose oxidase. We have identified these compounds as long-chain aliphatic aldehydes, mainly palmitic aldehyde C15H31CH=O and stearic aldehyde C17H35CH=O. We have further found that the aldehydes originate from plasmalogens present in the phospholipid fraction of the mucous obtained from colorectal cancer patients. The aldehydes, present in plasmalogens as enol ethers, are released by the acidity of the Schiff reagent and in turn react with the Schiff reagent to form the coloured adducts. Correct identification of these markers could lead to the development of a more accurate colorectal cancer screening tool and to a deeper understanding of colorectal carcinogenesis.
Muraki,Mukaiyama
, p. 875 (1975)
A dicarboxylic fatty acid derivative of paclitaxel for albumin-assisted drug delivery
Hackett, Michael J.,Joolakanti, Shyamsunder,Hartranft, Megan E.,Guley, Patrick C.,Cho, Moo J.
, p. 3292 - 3304 (2012)
Paclitaxel (PTX) is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently, the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection, resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize PTX by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3-pentadecylglutaric (PDG) acid, which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (～5% over 72h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor-bearing mice, [3H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 h. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23h half-life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics.
Short asymmetric syntheses of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer
Da Silva Pinto, Solange,Davies, Stephen G.,Fletcher, Ai M.,Newton, Sophie K.,Roberts, Paul M.,Thomson, James E.
supporting information, (2021/02/09)
A short asymmetric synthesis of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer is reported. The synthesis of sphinganine employs diastereoselective aminohydroxylation of tert-butyl 2-octadecenoate [conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide, then in situ enolate oxidation with (+)-camphorsulfonyloxaziridine (CSO)] and a stereospecific rearrangement of the resultant anti-α-hydroxy-β-amino ester into the corresponding anti-α-amino-β-hydroxy ester. Final hydrogenolysis and ester reduction completes the synthesis of the sphingoid base target. The synthesis of the C(2)-epimer follows a similar route, incorporating a diastereoselective reduction protocol to transform the anti-α-hydroxy-β-amino ester into its syn-α-hydroxy-β-amino ester counterpart.
Synthesis of (+/-)-Pregabalin and its novel lipophilic β-alkyl-substituted analogues from fatty chains
D'Oca, Caroline Da Ros Montes,Mass, Eduardo Bustos,Ongaratto, Renata Fontes,De Andrade, Arthur Motta,D'Oca, Marcelo G. Montes,Russowsky, Dennis
, p. 13230 - 13239 (2020/08/28)
In this work, were synthesized for the first time a series of new lipophilic β-alkyl substituted GABA derivatives from fatty alkyl chains. The synthesis of these GABA analogues was investigated by two different bicomponent approaches as a key step. The results showed low yields in the path from aliphatic nitroolefins and Meldrum's acid, whereas the Knoevenagel condensation between aliphatic aldehydes and Meldrum's acid afforded fatty alkylidenes in good yields (75-97%). These compounds were subsequently subjected to a conjugate addition reaction with nitromethane, resulting in the fatty Michael adducts (in 87-97% yields) which were in turn submitted to a one pot domino hydrolysis-decarboxylation, leading to the isolation of β-alkyl-substituted γ-nitro acids in good yields (78-92%). Finally, the reduction of the fatty γ-nitro acids allowed for the access to new lipophilic β-alkyl substituted GABA analogues, which were isolated in high yields (90-98%). The new methodology was also applied to the synthesis of antiepileptic drug (+/-)-Pregabalin, which was obtained after four steps in high overall yield. This journal is
