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Synlett 2016; 27(09): 1354-1358
DOI: 10.1055/s-0035-1561570
DOI: 10.1055/s-0035-1561570
letter
An Easy Route to Enantiomerically Enriched 7- and 8-Hydroxystearic Acids by Olefin-Metathesis-Based Approach
Further Information
Publication History
Received: 25 September 2015
Accepted after revision: 18 January 2016
Publication Date:
17 February 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201609/lookinside/thumbnails/st-2015-b0766-l_10-1055_s-0035-1561570-1.jpg)
Abstract
The synthesis of enantiomerically enriched 7- and 8-hydroxystearic acids (7- and 8-HSA) has been successfully accomplished starting from chiral nonracemic 1-pentadecen-4-ol and 1-tetradecen-4-ol, respectively. Their Yamaguchi’s esterification with 4-pentenoic and 5-hexenoic acids, respectively, afforded the suitable dienic esters which were submitted to ring-closing metathesis reaction. After hydrogenation and basic hydrolysis of the complex reaction mixture, chiral nonracemic 7- and 8-HSA were obtained in about 40% total yield.
Key words
hydroxystearic acid - ring closing metathesis - cross metathesis - homoallylic alcohols - lipase B from Candida antarctica - kinetic enzymatic resolutionSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561570.
- Supporting Information
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References and Notes
- 1a Gunstone FD. Fatty Acid and Lipid Chemistry . Springer; Berlin: 1996
- 1b Fulco AJ. Progr. Lipid Res. 1983; 22: 133
- 1c Harwood JL, Russell NJ. Lipids in Plants and Microbes . Allen and Unwin; London: 1984
- 2a Masotti L, Casali E, Gesmundo N, Sartor G, Galeotti T, Borrello S, Piretti MV, Pagliuca G. Ann. N.Y. Acad. Sci. 1989; 51: 47
- 2b Masotti L, Casali E, Gesmundo N. Mol. Aspects Med. 1993; 14: 209
- 2c Bertucci C, Hudaib M, Boga C, Calonghi N, Cappadone C, Masotti L. Rapid Commun. Mass Spectrom. 2002; 16: 859
- 3 Parolin C, Calonghi N, Presta E, Boga C, Caruana P, Naldi M, Andrisano V, Masotti L, Sartor G. Biochim. Biophys. Acta 2012; 1821: 1334
- 4 Cristofolini L, Fontana MP, Boga C, Konovalov O. Langmuir 2005; 21: 11213
- 5a Rogers MA, Wright AJ, Marangoni AG. Soft Matter 2008; 4: 1483
- 5b Rogers MA, Wright AJ, Marangoni AG. Curr. Opin. Coll. Interf. Sci. 2009; 14: 33
- 5c Rogers MA, Kim JH. J. Food Res. Int. 2011; 44: 1447
- 6a Mallia VA, Weiss RG. J. Phys. Org. Chem. 2014; 27: 310
- 6b Abraham S, Lan Y, Lam RS. H, Grahame DA. S, Kim JJ. H, Weiss RG. A, Rogers MA. Langmuir 2012; 28: 4955
- 7 Laupheimer M, Preisig N, Stubenrauch C. Colloids Surf., A 2015; 469: 315
- 8a Grahame DA. S, Olauson C, Lam RS. H, Pedersen T, Borondics F, Abraham S, Weiss RG, Rogers MA. Soft Matter 2011; 7: 7359
- 8b Tachibana T, Kambara H. J. Colloid Interface Sci. 1968; 28: 173
- 8c Tachibana T, Mori T, Hori K. Bull. Chem. Soc. 1980; 53: 1714
- 9 Badami RC, Patil KB. Prog. Lipid Res. 1981; 19: 119 ; and references cited therein
- 10 Murakami S, Satou K, Kijima T, Watanabe M, Izumi T. Eur. J. Lipid Sci. Technol. 2011; 113: 450
- 11 Miller RW, Weisleder D, Kleiman R, Plattnera RD, Smith CR. Jr. Phytochemistry 1977; 16: 947
- 12a Bowers S, Hoch HC, Evans PH, Katayama M. Science 1986; 232: 105
- 12b Brodowsky ID, Oliw EH. Biochim. Biophys. Acta 1993; 1168: 68
- 12c Garscha U, Oliw EH. Anal. Biochem. 2007; 367: 238 ; and references cited therein
- 13 Ebert C, Felluga F, Forzato C, Foscato M, Gardossi L, Nitti P, Pitacco G, Boga C, Caruana P, Micheletti G, Calonghi N, Masotti L. J. Mol. Catal. B: Enzym. 2012; 83: 38
- 14 Wetzel I, Krauss J, Bracher F. Lett. Org. Chem. 2012; 9: 169
- 15 Harbindu A, Sharma MB, Kumar P. Tetrahedron: Asymmetry 2013; 24: 305
- 16 Kumar RS. C, Sreedhar E, Reddy GV, Babu KS, Rao JM. Tetrahedron: Asymmetry 2009; 20: 1160
- 17 Ishiyama T, Ahiko T, Miyaura N. J. Am. Chem. Soc. 2002; 124: 12414
- 18a Hodgson DM, Fleming MJ, Stanway SJ. J. Org. Chem. 2007; 72: 4763
- 18b Hodgson DM, Fleming MJ, Stanway SJ. J. Am. Chem. Soc. 2004; 126: 12250
- 19a Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn. 1979; 52: 1989
- 19b Chatterjee B, Mondal D, Bera S. Tetrahedron: Asymmetry 2012; 23: 1170
- 20 Chang Y.-H, Uang B.-J, Wu C.-M, Yu T.-H. Synthesis 1990; 1033
- 21 Chen CS, Fujimoto Y, Girdaukas G, Sih CJ. J. Am. Chem. Soc. 1982; 104: 72
- 22 Hanessian S, Tehim A, Chen P. J. Org. Chem. 1993; 58: 7768
- 23 Ghosh AK, Liu C. Chem. Commun. 1999; 1743
- 24 Tripathi D, Kumar P. Tetrahedron: Asymmetry 2012; 23: 884
- 25 Adlhart C, Chen P. J. Am. Chem. Soc. 2004; 126: 3496
-
26 Lee CW, Grubbs RH. J. Org. Chem. 2001; 66: 7155
- 27 Typical Procedure To (–)-(S)-4a (0.143 g, 0.46 mmol) in anhydrous CH2Cl2 (14 mL), Ti(Oi-Pr)4 (0.41 mL, 1.38 mmol) was added at room temperature. The stirred solution was refluxed under Ar for 30 min and then left cooled for 15 min. Second-generation Grubbs catalyst (0.0236 g, 0.027 mmol) dissolved in anhydrous CH2Cl2 (1 mL) was added, the reaction was refluxed with stirring for 7 h in Ar atmosphere then left at room temperature overnight. The solution was filtered on a SiO2 pad, and washed with CH2Cl2. The solvent was evaporated, and to the crude reaction mixture (0.095 g) MeOH (4.75 mL) and Pd/C (10%, 0.095 g) were added. The reaction mixture was stirred under H2 atmosphere for 24 h, then filtered on a short column of SiO2, and washed with CH2Cl2. The solvent was evaporated, and the crude was treated with 3.0 mL of 10% KOH/MeOH, the mixture was stirred at 46 °C for 3 d. After removing the solvent, H2O (10 mL) was added and repeatedly extracted with Et2O. The organic phase was dried on anhydrous Na2SO4 and evaporated to afford diol 11a (0.0045 g, 0.01 mmol). Basic mother liquors were acidified to pH 1 and extracted with Et2O. The organic phase was dried on anhydrous Na2SO4 and evaporated to furnish the acid (S)-7-HSA (1a, 0.038 g, 0.12 mmol). Evaporation of acidic mother liquors furnished diacid 12a. The same procedure was applied on (+)-(R)-4a.
- 28 Mitchell L, Parkinson JA, Percy JM, Singh K. J. Org. Chem. 2008; 73: 2389
-
29a Hong SH, Sanders DP, Lee CW, Grubbs RH. J. Am. Chem. Soc. 2005; 127: 17160
- 29b Lehman SE. Jr, Schwendeman JE, O’Donnell PM, Wagener KB. Inorg. Chim. Acta 2003; 345: 190
- 29c Schmidt B. Eur. J. Org. Chem. 2004; 1865
- 30 Illuminati G, Mandolini L. Acc. Chem. Res. 1981; 14: 95
- 31 Kadyrov R. Chem. Eur. J. 2013; 19: 1002 ; and references cited therein
-
32 Monfette S, Fogg DE. Chem. Rev. 2009; 109: 3783
- 33 For derivatization with (R)-(–)-O-acetylmandelic acid and related 1H NMR signals, see ref. 13. The diastereomeric ratio was calculated on the crude for (R)-7- and (R)-8-HSA derivatives and on the product purified by preparative TLC for (S)-7- and (S)-8-HSA derivatives.
- 34 General Procedure for Derivatization with Mosher Acid (R)-(+)-α-Methoxy-α-trifluoromethylphenylacetic acid [(+)-MTPA, for derivatization of 7-HSA methyl esters] (0.012 g), or (S)-(–)-α-methoxy-α-trifluorophenylacetic acid [(–)-MTPA, for 8-HSA methyl esters], and DMAP (0.003 g) were dissolved, under nitrogen atmosphere, in anhydrous CH2Cl2 (300 μL) and stirred at 0 °C (ice-bath). To this solution of methyl hydroxystearate (0.008 g) and DCC (0.010 g) dissolved in anhydrous CH2Cl2 (500 μL) was added dropwise. After a few minutes, a white solid precipitated. The reaction was monitored by TLC (eluent: n-hexane–EtOAc, 3:1) until completion (sometimes addition of a further amount of DCC and DMAP was necessary to reach completion). The solvent was removed, and the crude was dissolved in CDCl3 and analyzed by 1H NMR and 19F NMR. The diastereomeric ratio was calculated by integration of the 19F NMR signals; hexafluorobenzene (δ = –163.0 ppm) was used as internal standard. (R)-Methyl 7-{[(R)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyl]oxy}octadecanoate [(7R,2′R)-14a] 1H NMR (400 MHz, CDCl3): δ = 7.58–7.50 (m, 2 H, Ph), 7.42–7.37 (m, 3 H, Ph), 5.07 (quint, 1 H, J = 6.4 Hz, CHOH), 3.66 (s, 3 H, COOCH3), 3.55 (br s, 3 H, OCH3), 2.28 (t, 2 H, J = 7.3 Hz, CH2CO), 1.80–1.40 (m, 6 H, CH2), 1.40–1.10 (m, 22 H, CH2), 0.88 (t, 3 H, J = 6.2 Hz, CH3) ppm. 19F NMR (376 MHz, CDCl3): δ = –72.360 ppm. (S)-Methyl 7-{[(R)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyl]oxy}octadecanoate [(7S,2′R)-14a] 1H NMR signals undiscernible from those of the 7R,2′R diastereomer. 19F NMR (376 MHz, CDCl3): δ = –72.323 ppm. (R)-Methyl 8-{[(S)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyl]oxy}octadecanoate [(8R,2′S)-14b] 1H NMR (400 MHz, CDCl3): δ = 7.59–7.50 (m, 2 H, Ph), 7.45–7.36 (m, 3 H, Ph), 5.07 (quint, 1 H, J = 6.5 Hz, CHOH), 3.67 (s, 3 H, COOCH3), 3.55 (br s, 3 H, OCH3), 2.27 (t, 2 H, J = 7.5 Hz, CH2CO), 1.82–1.40 (m, 6 H, CH2), 1.40–1.10 (m, 22 H, CH2), 0.87 (t, 3 H, J = 7.0 Hz, CH3) ppm. 19F NMR (376 MHz, CDCl3): δ = –72.369 ppm. (S)-Methyl 8-{[(S)-3,3,3-Trifluoro-2-methoxy-2-phenylpropanoyl]oxy}octadecanoate [(8S,2′S)-14b] 1H NMR signals are undiscernible from those of the 8R,2′S diastereomer. 19F NMR (376 MHz, CDCl3): δ = –72.405 ppm.