New chemoenzymatic synthesis of (±)-n-(2-hydroxyethyl)-n,n-dime thyl- 2,3-bis(tetradecyloxy)-1-propanammonium bromide (dmrie)
Background: Cytofectins are a class of positively charged lipid molecules that can facilitate the functional entry of polynucleotides, macromolecules, and small molecules into living cells, escaping lysosomal degradation. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMR...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | |
| Formato: | Capítulo de libro |
| Lenguaje: | Inglés |
| Publicado: |
Bentham Science Publishers B.V.
2016
|
| Acceso en línea: | Registro en Scopus Handle Registro en la Biblioteca Digital |
| Aporte de: | Registro referencial: Solicitar el recurso aquí |
| Sumario: | Background: Cytofectins are a class of positively charged lipid molecules that can facilitate the functional entry of polynucleotides, macromolecules, and small molecules into living cells, escaping lysosomal degradation. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver differents active molecules into animal and human diseased tissues. To our knowledge, two synthetic routes for the preparation of DMRIE have so far been reported. One of them is based on the reaction of epichlorhydrin with either dimethylamine chloride or dimethylamine using an alkaline solution as solvent. The main disadvantage of these routes is the formation of 3-(N,N-diamino)-1,2-propanediol. In summary, the synthetic routes mentioned use epichlorohydrin or glycidol as starting materials, both of which have been described as carcinogenic agents. Additionally, sometimes the reaction conditions are drastic. An alternative route for the preparation of other cytofectins is the use of glycerol as the starting material. Glycerol is a non-carcinogenic compound, but its use as starting material results in an increased number of steps of this reaction, generating an increase in the total time of synthesis and the formation of a greater amount of waste and scrap. Based on the above, here we propose a new chemoenzymatic synthetic strategy using glycerol as a starting material. Methods: Initially, glycerol and vinyl benzoate were mixed in presence of Mucor miehei lipase (Lipozyme), it is converted into corresponding mono-benzoate (±)-1. Finally, DMRIE was obtained by the reaction of bromide (±)-3 with 2- dimethylaminoethanol (DMAE). Results: We studied the stability of compound (±)-1 under the working conditions applied in the preparation of intermediate alcohol (±)-2. Additionally, we study different experimental parameters. Conclusion: In summary, a new chemoenzymatic synthetic route was developed for the DMRIE using glycerol as the starting material. We studied and optimized various experimental parameters of the various synthetic steps, and reached to develop the methodology to multigram scale, which compared to processes reported so far, has the advantages of fewer synthetic steps, the use of less aggressive reagents environment and generating fewer waste allowed to obtain the desired product; which results in a viable method for synthesizing analogs to DMRIE. © 2016 Bentham Science Publishers. |
|---|---|
| Bibliografía: | Miller, A.D., (2004) Suicide Gene Therapy Methods and Reviews Methods in Molecular Medicine, 90, pp. 107-137. , Springer, C. J.; Ed.; Humana Press Inc.: Totowa Rosenthal, A.F., Geyer, R.P., A synthetic inhibitor of venom lecithinase a (1960) J. Biol. Chem, 235, pp. 2202-2206 Wheeler, J.C., Suklu, L., Yang, G., Tsai, Y., Bustamante, C., Felgner, P., Norman, J., Manthorpe, M., Convertion an alcohol to an amine in cationic lipid dramatically alters the co-lipid requirement, cellular transfection activity and the ultrastructure of DNAcytofectin complexes (1996) Biochem. Biophys. Acta, 1280, pp. 1-11 Yin, H., Kanasty, R.L., Eltoukhy, A.A., Vegas, A.J.J., Dorkin, R., Anderson, D.G., Non-viral vectors for gene-based therapy (2014) Nature Rev. Genet, 15, pp. 541-555 Villaverde, M.S., Combe, K., Duchene, A.G., Wei, M.X., Glikin, G.C., Finocchiaro, L.M.E., Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting (2014) Int. Immunopharmacol, 22, pp. 167-175 Wong, A.W., Baginski, T.K., Reilly, D.E., Enhancement of DNA uptake in FUT8-deleted CHO cells for transient production of afucosylated antibodies (2011) Biotechnol. Bioeng, 106, pp. 751-763 Masotti, A., Mossa, G., Cametti, C., Ortaggi, G., Bianco, A., Del Grosso, N., Malizia, D., Esposito, C., Comparison of different commercially available cationic liposome-DNA lipoplexes: Parameters influencing toxicity and transfection efficiency (2009) Colloids and Surfaces B: Biointerfaces, 68, pp. 136-144 Ferrari, M.E., Rusalov, D., Enas, J., Wheeler, C.J., Synergy between cationic lipid and co-lipid determines the macroscopic structure and transfection activity of lipoflexes (2002) Nucleic Acids. Res, 30, pp. 1808-1816 Li, J., Wang, X., Zhang, T., Wang, C., Huang, Z., Luo, X., Deng, Y., A review on phospholipids and their main applications in drug delivery systems (2015) Asian J Pharm Sci, 10, pp. 81-98 Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Liposome, K., Classification, preparation, and applications. Nanoscale (2013) Res. Lett, 102, pp. 1-9 Felgner, J.H., Kumar, R., Sridhar, C.N., Wheeler, C.J., Tsai, Y.J., Border, R., Ramsey, P., Felgner, P.L., Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations (1994) J. Biol. Chem, 289, pp. 2550-2561 Kasireddy, K., Ali, S.M., Ahmad, M.U., Choudhury, S., Chien, P.-Y., Sheikh, S., Ahmad, I., Synthesis of cationic cardiolipin analogues (2005) Bioorg. Chem, 33, pp. 345-362 Xiang, S., Shuanling, Z., Zeng, Y., Zhang, J., Zhao, C., Liu, S., Liu, M., Hu, X., (2013) Propylene glycol amine derivate cationic liposome nano particles and preparation method thereof, , April 12 Konishi, Y., Kawabata, A., Denda, A., Ikeda, T., Katada, H., Maruyama, H., Higashiguchi, R., Forestomach tumors induced by orally administered epichlorohydrin in male (1980) Wistar Rats Gan, 71, pp. 922-923 Wester, P.W., Van Der Heijden, C.A., Bisschop, A., Van Esch, G.J., Carcinogenicity study with epichlorohydrin (CEP) by gavage in rats (1985) Toxicology, 36, pp. 325-339 Laskin, S., Sellakumar, A.R., Kuschner, M., Nelson, N., La Men Dola, S., Rusch, G.M., Katz, G.V., Albert, R.E., Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats (1980) J. Natl. Cancer Lnst, 65, pp. 751-757 Irwin, R.D., Eustis, S.L., Stefanski, S., Haseman, J.K., Carcinogeni city of Glycidol in F344 rats and B6C3F1 mice (1996) J. Appl. Toxicol, 16, pp. 201-209 Lijinsky, W., Kovatch, R.M., A study of carcinogenicity of glycidol in Syrian hamsters (1992) Toxicol. and Health, 8, pp. 267-271 1,2-Bis-tetradecyloxy-3-O-benzylpropane: (1.03 g, 1.7 mmol) was dissolved in ethyl acetate (10 mL) and hydrogenated with 10% palladium on carbon (0.15 g) for 36 h at 14.7 psi. After filtration of the catalyst, the solution was evaporated under reduced pressure, purification by chromatography column on silica gel with hexane afforded 0.470 g (yield: 80%) of (±)-2 as a white solid; Kato, Y., Fujiwara, I., Asano, Y., A novel method for preparation of optically active -monobenzoyl glycerol via lipase-catalyzed asymmetric transesterification of glycerol (1999) Bioorg. Med. Chem. Lett, 9, pp. 3207-3210 Kato, Y., Fujiwara, I., Asano, Y., Synthesis of optically active -monobenzoyl glycerol by asymmetric transesterification of glycerol (2000) J Mol. Catal. B: Enzym, 9, pp. 193-200 Xu, J.-H., Kato, Y., Asano, Y., Efficient preparation of (R)-monobenzoyl glycerol by lipase catalyzed asymmetric esterification: Optimization and operation in packed bed reactor (2001) Biotechnol. Bioeng, 73, pp. 493-499 Casati, S., Ciuffreda, P., Santaniello, E., Synthesis of enantio merically pure (R)-And (S)-1-benzoyloxypropane-2,3-diol and revision of the stereochemical outcome of the Candida antarctica lipasecatalyzed benzoylation of glycerol (2011) Tetrahedron -Asymmetr, 22, pp. 658-611 Chena, J.-S., Barton, P.G., Studies of dialkyi ether phospholipids. I I. Requirement for a liquid-crystalline sobstrate for hydrolysis by cabbage leaf phospholipase d (1971) Can. J. Biochem, 49, pp. 1362-1375 Morozova, N.G., Maslov, M.A., Petukhova, O.A., Andronova, O.A., Grishaeva, O.A., Serebrennikova, O.A., Synthesis of lipid mediators based on 1,2dialkylglycerol and cholesterol for targeted delivery of oligo and polynucleotides into hepatocytes (2011) Russ. Chem. Bull, 59, pp. 251-259 |
| ISSN: | 15701786 |