Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2020; 31(07): 718-722
DOI: 10.1055/s-0039-1691584
DOI: 10.1055/s-0039-1691584
letter
Synthesis of Phosphatidylcholines Possessing Functionalized Acids at sn-2, and 13C–14N and 13C–31P Couplings in Their 13C NMR Spectra
This work was supported in part by the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant No. JP15H05904 (Y.K.), JP15H05897 (M.A.), and JP15H05898 (M.A.).Further Information
Publication History
Received: 04 November 2019
Accepted after revision: 08 January 2020
Publication Date:
28 January 2020 (online)
Abstract
Although 4-Me2NC5H4N (DMAP) is a standard base for esterification of (2-Me-6-NO2-C6H3CO)2O (MNBA), N-methylimidazole (NMI) was examined for the condensation of acids with 1-stearoyl-lysophosphatidylcholine because of the non-tailing nature of NMI on silica gel. Acids tested were EPA, α-linolenic acid, TBS ethers of 18-HEPE and ricinoleic acid, acid-labile epoxy acids, and a phenyldiynyl acid. The condensation proceeded well with these acids, and chromatographic separation of resulting phosphatidylcholines and remaining NMI was easily performed. During the characterization of the products by 13C NMR spectroscopy, 13C–14N and 13C–31P couplings were observed.
Key words
synthesis - lyso-phosphatidylcholine - functionalized acid - Shiina reagent - N-methylimidazole - 13C–14N couplingSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691584.
- Supporting Information
-
References and Notes
- 1 Present address: Research Foundation ITSUU Laboratory, C1232 Kanagawa Science Park R&D Building, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan.
- 2 Present address: Meiji University, Organization for the Strategic Coordination of Research and Intellectual Properties, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.
- 3 Shimanaka Y, Kono N, Taketomi Y, Arita M, Okayama Y, Tanaka Y, Nishito Y, Mochizuki T, Kusuhara H, Adibekian A, Cravatt BF, Murakami M, Arai H. Nat. Med. 2017; 23: 1287
- 4 Caires R, Sierra-Valdez FJ, Millet JR. M, Herwig JD, Roan E, Vásquez V, Cordero-Morales JF. Cell Rep. 2017; 21: 246
- 5 Slatter DA, Percy CL, Allen-Redpath K, Gajsiewicz JM, Brooks NJ, Clayton A, Tyrrell VJ, Rosas M, Lauder SN, Watson A, Dul M, Garcia-Diaz Y, Aldrovandi M, Heurich M, Hall J, Morrissey JH, Lacroix-Desmazes S, Delignat S, Jenkins PV, Collins PW, O'Donnell VB. JCI Insight 2018; 3: e98459
- 6 Siegel TP, Ekroos K, Ellis SR. Angew. Chem. Int. Ed. 2019; 58: 6492
- 7 Ryan E, Reid GE. Acc. Chem. Res. 2016; 49: 1596
- 8a Onyango AN, Inoue T, Nakajima S, Baba N, Kaneko T, Matsuo M, Shimizu S. Angew. Chem. Int. Ed. 2001; 40: 1755
- 8b Sun M, Deng Y, Batyreva E, Sha W, Salomon RG. J. Org. Chem. 2002; 67: 3575
- 8c Tan C, Fung BM, Cho G. J. Am. Chem. Soc. 2002; 124: 11827
- 8d Gu X, Sun M, Gugiu B, Hazen S, Crabb JW, Salomon RG. J. Org. Chem. 2003; 68: 3749
- 8e Spite M, Baba SP, Ahmed Y, Barski OA, Nijhawan K, Petrash JM, Bhatnagar A, Srivastava S. Biochem. J. 2007; 405: 95
- 8f O’Neil EJ, DiVittorio KM, Smith BD. Org. Lett. 2007; 9: 199
- 8g Lampkins AJ, O’Neil EJ, Smith BD. J. Org. Chem. 2008; 73: 6053
- 8h Mesaros C, Gugiu BG, Zhou R, Lee SH, Choi J, Laird J, Blair IA, Salomon RG. Chem. Res. Toxicol. 2010; 23: 516
- 8i Long JZ, Cisar JS, Milliken D, Niessen S, Wang C, Trauger SA, Siuzdak G, Cravatt BF. Nat. Chem. Biol. 2011; 7: 763
- 8j Xia Y, Qu F, Maggiani A, Sengupta K, Liu C, Peng L. Org. Lett. 2011; 13: 4248
- 8k Niezgoda N, Gliszczyńska A, Gładkowski W, Kempińska K, Wietrzyk J, Wawrzeńczyk C. Aust. J. Chem. 2015; 68: 1065
- 9 Acharya HP, Kobayashi Y. Angew. Chem. Int. Ed. 2005; 44: 3481
- 10a Acharya HP, Kobayashi Y. Tetrahedron Lett. 2005; 46: 8435
- 10b Acharya HP, Miyoshi K, Kobayashi Y. Org. Lett. 2007; 9: 3535
- 10c Acharya HP, Miyoshi K, Takashima Y, Ogawa N, Kobayashi Y. Heterocycles 2008; 76: 1181
- 11 Acharya HP, Kobayashi Y. Synlett 2005; 2015
- 12a Jung ME, Berliner JA, Angst D, Yue D, Koroniak L, Watson AD, Li R. Org. Lett. 2005; 7: 3933
- 12b Jung ME, Berliner JA, Koroniak L, Gugiu BG, Watson AD. Org. Lett. 2008; 10: 4207
- 12c Egger J, Bretscher P, Freigang S, Kopf M, Carreira EM. Angew. Chem. Int. Ed. 2013; 52: 5382
- 12d Enomoto T, Brea RJ, Bhattacharya A, Devaraj NK. Langmuir 2018; 34: 750
- 13a Choi J, Laird JM, Salomon RG. Bioorg. Med. Chem. 2011; 19: 580
- 13b Guimond-Tremblay J, Gagnon M.-C, Pineault-Maltais J.-A, Turcotte V, Auger M, Paquin J.-F. Org. Biomol. Chem. 2012; 10: 1145
- 13c Gagnon M.-C, Turgeon B, Savoie J.-D, Parent J.-F, Auger M, Paquin J.-F. Org. Biomol. Chem. 2014; 12: 5126
- 15a Yasuda T, Kinoshita M, Murata M, Matsumori N. Biophys. J. 2014; 106: 631
- 15b Cui J, Lethu S, Yasuda T, Matsuoka S, Matsumori N, Sato F, Murata M. Bioorg. Med. Chem. Lett. 2015; 25: 203
- 15c Yasuda T, Tsuchikawa H, Murata M, Matsumori N. Biophys. J. 2015; 108: 2502
- 15d Lindner S, Gruhle K, Schmidt R, Garamus VM, Ramsbeck D, Hause G, Meister A, Sinz A, Drescher S. Langmuir 2017; 33: 4960
- 16a Xia J, Hui Y.-Z. Tetrahedron: Asymmetry 1997; 8: 451
- 16b Budin I, Devaraj NK. J. Am. Chem. Soc. 2012; 134: 751
- 16c Cole CM, Brea RJ, Kim YH, Hardy MD, Yang J, Devaraj NK. Angew. Chem. Int. Ed. 2015; 54: 12738
- 16d Ng CY, Kwok TX. W, Tan FC. K, Low C.-M, Lam Y. Chem. Commun. 2017; 53: 1813
- 17 Murari R, Baumann WJ. J. Am. Chem. Soc. 1981; 103: 1238
- 18 Bruzik K, Jiang R.-T, Tsai M.-D. Biochemistry 1983; 22: 2478
- 19 Taniguchi T, Manai D, Shibata M, Itabashi Y, Monde K. J. Am. Chem. Soc. 2015; 137: 12191
- 21 Phosphatidylcholines were easily soluble in CD3OD. The couplings were observed in CD3OD not in CDCl3.
- 22 Brown CA, Ahuja VK. J. Chem. Soc., Chem. Commun. 1973; 553
- 23 Nanba Y, Shinohara R, Morita M, Kobayashi Y. Org. Biomol. Chem. 2017; 15: 8614
- 24a A diagnostic signal for the acyl migration product of lyso-PCs appears at δ = 5.0 ppm.24b However, NMI (4.5 equiv) gave the migration product of 2a in 1% after 48 h at rt in CH2Cl2 (see Supporting Information).
- 24b Kim Y.-A, Park M.-S, Kim YH, Han S.-Y. Tetrahedron 2003; 59: 2921
- 25 To a solution of acid 1a (48 mg, 0.192 mmol) in CH2Cl2 (1 mL) were added NMI (0.034 mL, 0.43 mmol) and MNBA (148 mg, 0.430 mmol). After 20 min of stirring at rt, lyso-PC 2a (50 mg, 0.0955 mmol) was added. The mixture was stirred at rt for 24 h under nitrogen and concentrated to give a residue, which was purified by chromatography on silica gel (CHCl3/MeOH/H2O = 65:25:1 to 65:25:3) to afford PC 3a (63 mg, 87%): Rf = 0.21 (CHCl3/MeOH/H2O = 65:25:3). 1H NMR (400 MHz, CD3OD): δ = 0.89 (t, J = 6.8 Hz, 3 H), 1.27 (br s), 1.53–1.88 (m, 6 H), 2.30 (t, J = 7.4 Hz, 2 H), 2.43–2.52 (m, 2 H), 2.72–2.83 (m, 2 H), 3.01 (dt, J = 7.2, 4.2 Hz, 1 H), 3.10–3.16 (m, 1 H), 3.21 (s, 9 H), 3.60–3.66 (m, 2 H), 3.76 (s, 9 H), 4.02 (t, J = 6.2 Hz, 2 H), 4.18 (dd, J = 12.0, 6.4 Hz, 1 H), 4.23–4.31 (m, 2 H), 4.44 (dd, J = 12.0, 2.8 Hz, 1 H), 5.22–5.29 (m, 1 H), 6.86 (dd, J = 8.4 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H). 13C NMR (100 MHz, CD3OD): δ = 13.1, 21.70, 21.73, 22.3, 24.6, 26.9, 28.8, 29.0, 29.1, 29.2, 29.4, 31.7, 32.9, 33.19, 33.21, 33.4, 53.3 (t, J = 3.8 Hz, 3 C), 54.2, 56.81 and 56.84, 57.50 and 57.53, 59.1 (d, J = 5.3 Hz), 62.2, 63.5 (d, J = 4.6 Hz), 66.0 (m), 70.6 (d, J = 7.6 Hz), 113.6, 129.4, 129.8, 158.5, 172.8, 173.6. HRMS (FAB): m/z calcd for C40H71O10NP [M + H]+ 756.4816; found: 756.4826.
- 26 Yamakoshi H, Dodo K, Palonpon A, Ando J, Fujita K, Kawata S, Sodeoka M. J. Am. Chem. Soc. 2012; 134: 20681
- 27 Luchetti L, Mancini G. Langmuir 2000; 16: 161
Other reagents: