Synthesis of the Anti-Melanogenic Glycerol Fatty Acid Ester Isolated from the Tuber-Barks of Colocasia antiquorum var. esculenta

Shijun Zhu; Yikang Wu

doi:10.1055/s-0033-1340078

Synlett, Table of Contents

Synlett 2014; 25(2): 261-264
DOI: 10.1055/s-0033-1340078

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Synthesis of the Anti-Melanogenic Glycerol Fatty Acid Ester Isolated from the Tuber-Barks of Colocasia antiquorum var. esculenta

Shijun Zhu

State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Email: yikangwu@sioc.ac.cn

,

Yikang Wu*

State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China Email: yikangwu@sioc.ac.cn

› Author Affiliations

Abstract

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Abstract

(2′S)-1-O-9-Oxo-(10E,12E)-octadecadienoyl glycerol, a natural anti-melanogenic monoglyceride, is synthesized for the first time. The chiral pool based route employed not only confirms the absolute configuration, but also illustrates the first synthetic entry to the (E,E)-diene keto acid, which is another molecule of biological importance. The confusion caused by the misinterpreted ¹H NMR spectroscopic data for the (E,E)-diene motif in the literature is discussed. The first unequivocal piece of evidence for the assigned (12E) configuration is also presented.

Key words

diols - acylation - glycerolipids - rearrangement - natural products

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References

References and Notes

1a Qi S.-H, Zhang S, Huang J.-S, Xiao Z.-H, Wu J, Long L.-J. Chem. Pharm. Bull. 2004; 52: 986
1b Omura S, Nakagawa A, Fukamachi N, Otaguro K, Kobayashi B. J. Antibiot. 1986; 39: 1180
1c Kitahara T, Aono S, Mori K. Biosci. Biotechnol., Biochem. 1995; 59: 78
1d Zeng X, Xiang L, Li C.-Y, Wang Y, Qiu G, Zhang Z.-x, He X. Fitoterapia 2012; 83: 609
1e Akeda Y, Shibata K, Ping X, Tanaka T, Taniguchi M. J. Antibiot. 1995; 48: 363
1f Wang J.-F, Dai H.-Q, Wei Y.-L, Zhu H.-J, Yan Y.-M, Wang Y.-H, Long C.-L, Zhong H.-M, Zhang L.-X, Cheng Y.-X. Chem. Biodivers. 2012; 7: 2046
1g Babady-Byla WH. Phytochemistry 1996; 42: 501
1h Hirao S, Tara K, Kuwano K, Tanaka J, Ishibashi F. Biosci., Biotechnol., Biochem. 2012; 76: 372
1i Okuyama E, Hasegawa T, Matsushita T, Fujimoto H, Ishibashi M, Yamazaki M. Chem. Pharm. Bull. 2001; 49: 154

For example, see:

2a Mori K. Tetrahedron 2012; 68: 8441
2b Stamatov SD, Stawinski J. Org. Biomol. Chem. 2007; 5: 3787
2c Neef AB, Schultz C. Angew. Chem. Int. Ed. 2009; 48: 1498
2d ter Horst B, Seshadri C, Sweet L, Young DC, Feringa BL, Moody DB, Minnaard AJ. J. Lipid Res. 2010; 51: 1017
2e Batovska DI, Tsubota S, Kato Y, Asanoa Y, Ubukatab M. Tetrahedron: Asymmetry 2004; 15: 3551
2f Rejzek M, Vacek M, Wimmer Z. Helv. Chim. Acta 2000; 83: 2756
2g Li A, Baker DL, Tigyi G, Bittman R. J. Org. Chem. 2006; 71: 629
2h Kubiak RJ, Bruzik KS. J. Org. Chem. 2003; 68: 960
2i Alcaraz M.-L, Peng L, Klotz P, Goeldner M. J. Org. Chem. 1996; 61: 192
2j Vaique E, Guy A, Couedelo L, Gosse I, Durand T, Cansell M, Pinet S. Tetrahedron 2010; 66: 8872
2k Redden PR, Lin X, Horrobin DF. Chem. Phys. Lipids 1996; 79: 9

3 Kim KH, Moon E, Kim SY, Lee KR. Bull. Korean Chem. Soc. 2010; 31: 2051

4a Feng S, Saw CL, Lee YK, Huang D. J. Agric. Food Chem. 2007; 55: 8589
4b Vollenweider S, Weber H, Stolz S, Chételat A, Farmer E. Plant J. 2000; 24: 467

5 Watanebe J, Kawabata J, Kasai T. Biosci., Biotechnol., Biochem. 1999; 63: 489

6a Kawagishi H, Miyazawa T, Kume H, Arimoto Y, Inakuma T. J. Nat. Prod. 2002; 65: 1712
6b Another study (the only available data in the literature other than ref. 6a, also measured in CDCl₃) similarly gave δ 6.19–6.15 (m 2 H) for the H-12 and H-13 protons, cf. ref. 8c.

7 Chen C.-Y, Han W.-B, Chen H.-J, Wu Y.-K, Gao P. Eur. J. Org. Chem. 2012; 4311

Despite its broad existence in Nature and importance in biology, no clear-cut routes to the (10E,12E) isomer exist to date (to our knowledge). For routes to the other isomers, see:

8a Tsuboi S, Maeda S, Takeda A. Bull. Chem. Soc. Jpn. 1986; 59: 2050
8b Iacazio G. Chem. Phys. Lipids 2003; 125: 114
8c Dufour A, Loonis M. Chem. Phys. Lipids 2005; 138: 60
8d Anterola A, Gobel C, Hornug E, Sellhorn G, Feussner I, Frimes H. Phytochemistry 2009; 70: 40

9 Guo C, Lu X. J. Chem. Soc., Perkin Trans. 1 1993; 1921

10a Sun M, Deng Y, Batyreva E, Sha W, Salomon RG. J. Org. Chem. 2002; 67: 3575
10b Jian Y.-J, Tang C.-J, Wu Y.-K. J. Org. Chem. 2007; 72: 4851

11 Schmidt HM, Arens JF. Recl. Trav. Chim. Pays-Bas 1967; 86: 1138

12a Nayyar NK, Hutchison DR, Martinelli MJ. J. Org. Chem. 1997; 62: 982
12b Allard M, Barnes K, Chen X, Cheung Y.-Y, Duffy B, Heap C, Inthavongsay J, Johnson M, Krishnamoorthy R, Manley C, Steffke S, Varughese D, Wang R, Wang Y, Schwartz CE. Tetrahedron Lett. 2011; 52: 2623

13a Smith CD, Tchabanenko K, Adlington RM, Baldwin JE. Tetrahedron Lett. 2006; 47: 3209
13b Fukuoka S, Nanri H, Katsuki T, Yamaguchi M. Tetrahedron Lett. 1987; 28: 6205

14 Direct treatment of 9 with the anion of alkyne 7 led to extensive formation of unidentified side products.
15 Here we deliberately stopped the hydrolysis early to ensure that no over-reaction/acyl migrations would occur.
16 A solution of acetonide 13 (91 mg, 0.22 mmol) in AcOH–H₂O (4:1 v/v, 2.3 mL) was stirred at 50 °C (oil bath) for 30 min. The heating bath was removed, and sat. aq NaHCO₃ solution (2 mL) was added followed by EtOAc (3 mL). The phases were separated and the aqueous layer was back-extracted with EtOAc (2 × 3 mL). The combined organic layers were washed with brine (3 mL) before being dried over anhydrous Na₂SO₄. Removal of the solvent on a rotary evaporator and column chromatography (PE–EtOAc, 2:1) on silica gel afforded diol 4 (53.9 mg, 66%) as a white solid along with unhydrolyzed starting 13 (31 mg, 0.075 mmol, 34%). Data for 4: Mp 52–54 °C; [α]_D ²⁶ +5.9 (c 0.12, MeOH), [α]_D ²⁶ +6.1 (c 1.00, MeOH), [α]_D ²⁷ +11.7 (c 0.12, DMSO), [α]_D ²⁷ +7.0 (c 0.54, DMSO), [α]_D ²⁷ +7.8 (c 1.00, DMSO) {Lit.³ [α]_D ²⁵ +4.28 (c 0.12, MeOH)}. IR (film of a concd soln in CH₂Cl₂): 3359 (br), 2928, 2852, 1732, 1682, 1634, 1596, 1471, 1406, 1376, 1332, 1310, 1236, 1223, 1182, 1118, 1045, 997 cm^–1. ¹H NMR (500 MHz, CD₃OD): δ = 7.23 (dd, J = 15.6, 9.8 Hz, 1 H), 6.33–6.21 (m, 2 H), 6.12 (d, J = 15.6 Hz, 1 H), 4.15 (dd, J = 11.4, 4.4 Hz, 1 H), 4.06 (dd, J = 11.4, 6.3 Hz, 1 H), 3.85–3.78 (m, 1 H), 3.56 (dd, J = 11.3, 5.4 Hz, 1 H), 3.53 (dd, J = 11.3, 5.7 Hz, 1 H), 2.60 (t, J = 7.4 Hz, 2 H), 2.35 (t, J = 7.4 Hz, 2 H), 2.20 (br q, J = 6.8 Hz, 2 H), 1.62 (quin, J = 6.9 Hz, 2 H), 1.58 (quin, J = 7.2 Hz, 2 H), 1.47 (quin, J = 7.4 Hz, 2 H), 1.39–1.30 (m, 10 H), 0.91 (t, J = 7.0 Hz, 3 H). ¹³C NMR (125 MHz, CD₃OD, with the solvent multiplet set at δ 48.0 as the internal reference): δ = 202.8, 174.4, 146.3, 144.3, 129.2, 127.8, 70.1, 65.5, 63.1, 40.0, 33.9, 33.1, 31.5, 29.15, 29.14, 29.0, 28.5, 24.9, 24.5, 22.5, 13.4. ESI-MS: m/z = 369.5 [M + H]⁺, 391.5 [M + Na]⁺. ESI-HRMS: m/z [M + Na]⁺ calcd for C₂₁H₃₆O₅Na: 391.2455; found: 391.2456.
17 The optical rotation for synthetic 4 was measured to be [α]_D ²⁵ +5.9 (c 0.12, MeOH) and [α]_D ²⁵ +6.1 (c 1.00, MeOH); cf. the data reported (see ref. 3) for natural 4: [α]_D ²⁵ +4.28 (c 0.12, MeOH).
18 It is worth mentioning that the ¹H and ¹³C NMR spectra of 4 recorded in CDCl₃ (see the Supporting Information) were very similar to those for its functionality regioisomer, (2′S)-1-O-13-oxo-(9E,11E)-octadecadienoyl glycerol,^6a another natural monoglyceride. However, small yet definite differences also exist, representing an interesting piece of evidence for differentiating these two closely related biologically important substances.
19 Ma D, Yu Y, Lu X. J. Org. Chem. 1989; 54: 1105
20 It appears that all previous investigators working with 6 and related compounds were not aware of the advantage of using benzene-d ₆. Otherwise, the lack of evidence for the (12E) configuration for 6 would not have gone unnoticed until now.
21 Since the (12E) configuration for compounds 5 and 4 in this work have now been secured by analysis of the ¹H NMR spectra in benzene-d ₆, the expansion of the ¹H NMR spectrum for the H-12 and H-13 region of acid 5 (and/or 4), recorded in CD₃OD or CDCl₃(both are much more commonly employed in synthesis than benzene-d ₆), provided in this work may thus be used as a quick reference for confirming the (12E) configuration for closely related compounds. One of the referees pointed out that the use of decoupling techniques could also provide pertinent information about the double-bond configuration.

Supplementary Material

Supporting Information