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DOI: 10.1055/s-2005-863752
Establishment of the Structure of Pinpollitol by Total Synthesis of the Proposed Putative Structures
Publikationsverlauf
Publikationsdatum:
09. März 2005 (online)
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Abstract
Proposed structures of pinpollitol, namely 1,4-di-O-methyl-chiro-inositol and 1,3-di-O-methyl-chiro-inositol, have been synthesized from myo-inositol. Racemic 1,4-di-O-methyl-chiro-inositol has been synthesized from the readily available 1,2:4,5-di-O-isopropylidene-myo-inositol, in five steps while dl-1,3-di-O-methyl-chiro-inositol from myo-inositol 1,3,5-orthoformate in nine steps. A comparison of the reported NMR data of pinpollitol with those of synthetic dimethyl ethers revealed that pinpollitol is d-1,4-di-O-methyl-chiro-inositol. Thus we have not only confirmed the structure of pinpollitol unambiguously but also achieved a rapid total synthesis of it from a cheaply available starting material, myo-inositol, in just six steps.
Key words
natural product - total synthesis - inositol - cyclitol - regioselectivity
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1a
Hinchliffe K.Irvine R. Nature 1997, 390: 123 -
1b
Phosphoinositides: Chemistry, Biochemistry and Biomedical Applications
Bruzik KS. ACS Symposium Series 718, Oxford University Press; Oxford: 1999. -
1c
Ferguson MAJ.Williams AF. Annu. Rev. Biochem. 1988, 57: 285 - Pinitol:
-
2a
Hudlicky T.Price JD.Rulin F.Tsunoda T. J. Am. Chem. Soc. 1990, 112: 9439 -
2b
Ley SV.Sternfeld F.Taylor S. Tetrahedron Lett. 1987, 28: 225 -
2c
Ley SV.Sternfeld F. Tetrahedron 1989, 45: 3463 -
2d
Jung PMJ.Motherwell WB.Williams AS. Chem. Commun. 1997, 1283 - Ononitol:
-
2e
Pietrusiewicz KM.Salamonczyk GM. Synth. Commun. 1995, 25: 1863 - Quebrachitol:
-
2f
Carless HAJ.Busia K.Oak OZ. Synlett 1993, 672 - 3
Gallagher RT. Phytochemistry 1975, 14: 755 - 4
Sureshan KM.Shashidhar MS.Praveen T.Das T. Chem. Rev. 2003, 103: 4477 - 5 Diketal 4 can be synthesized from myo-inositol in one step. See:
Gigg J.Gigg R.Payne S.Conant R. Carbohydr. Res. 1985, 142: 132 - 6
Sureshan KM.Yamasaki T.Hayashi M.Watanabe Y. Tetrahedron: Asymmetry 2003, 14: 1771 ; and references cited therein - 11
Lee HW.Kishi Y. J. Org. Chem. 1985, 69: 4402 - 12
Westerduin P.Willems HAM.van Boeckel CAA. Tetrahedron Lett. 1990, 31: 6915 -
16a
Kwon Y.-K.Lee C.Chung S.-K. J. Org. Chem. 2002, 67: 3327 -
16b
Suzuki T.Suzuki ST.Yamada I.Koashi Y.Yamada K.Chida N. J. Org. Chem. 2002, 67: 2874 -
16c
Chida N.Ogawa S. Chem. Commun. 1997, 807 ; and references cited therein -
16d
Suzuki T.Tanaka S.Yamada I.Koashi Y.Yamada K.Chida N. Org. Lett. 2000, 2: 1137 -
16e
Chida N.Yoshinaga M.Tobe T.Ogawa S. Chem. Commun. 1997, 1043 -
16f
Akiyama T.Ohnari M.Shima H.Ozaki S. Synlett 1991, 831 - 17
Sureshan KM.Shashidhar MS.Varma AJ. J. Org. Chem. 2002, 67: 6884 ; and references cited therein -
18a
Hosoda A.Miyake Y.Nomura E.Taniguchi H. Chem. Lett. 2003, 32: 1042 -
18b
Watanabe Y.Miyasou T.Hayashi M. Org. Lett. 2004, 6: 1547 -
18c
Sureshan KM.Yamaguchi K.Sei Y.Watanabe Y. Eur. J. Org. Chem. 2004, 4703 - 19
Akiyama T.Hara M.Fuchibe K.Sakamoto S.Yamaguchi K. Chem. Commun. 2003, 1734 - 20
Sureshan KM.Gonnade RG.Shashidhar MS.Puranik VG.Bhadbhade MM. Chem. Commun. 2001, 881 -
21a
Akiyama T.Nishimoto H.Ishikawa K.Ozaki S. Chem. Lett. 1992, 447 -
21b
Akiyama T.Horiguchi N.Ida T.Ozaki S. Chem. Lett. 1995, 975
References
Crystallographic data are deposited as CCDC 236206. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033, e-mail: deposit@ccdc.cam.ac.uk].
8Analytical data: 1H NMR (400 MHz, CDCl3): δ = 1.35 (s, 3 H, CH3), 1.48 (s, 6 H, 2 × CH3), 1.50 (s, 3 H, CH3), 3.44 (dd, 1 H, J = 10.3, 5.9 Hz, H-3), 3.560 (s, 3 H, OCH3), 3.564 (s, 3 H, OCH3), 3.79 (dd, 1 H, J = 10.3, 2.4 Hz, H-5), 3.96 (t, 1 H, J = 10.3 Hz, H-4), 4.02 (t, 1 H, J = 2.4, 2.0 Hz, H-6), 4.14 (t, 1 H, J = 5.9 Hz, H-2), 4.30 (dd, 1 H, J = 5.9, 2.0 Hz, H-1). 13C NMR (100.4 MHz, CDCl3): δ = 25.60 (CH3), 26.50 (CH3), 27.10 (CH3), 27.80 (CH3), 58.50 (OCH3), 60.00 (OCH3), 74.70, 74.73, 77.26, 78.01, 80.64 (C-3 or C-6), 84.78 (C-6 or C-3), 109.24 (O-C-O), 111.34 (O-C-O).
9Analytical data: mp 189-192 °C. 1H NMR (400 MHz, D2O): δ = 3.33 (t, 1 H, J = 9.6 Hz, H-4), 3.43 (s, 3 H, CH 3), 3.60 (t, 1 H, J = 9.6 Hz, H-3), 3.60 (s, 3 H, CH 3), 3.64 (t, 1 H, J = 3.6 Hz, H-1), 3.74 (dd, 1 H, J = 9.6, 3.6 Hz, H-5), 3.81 (dd, 1 H, J = 10.0, 3.6 Hz, H-2), 4.22 (t, 1 H, J = 3.6 Hz, H-6). (13C NMR (100.4 MHz, D2O, dioxane reference at 66.5 ppm): δ = 58.5, 59.6, 68.0, 69.8, 70.2, 72.3, 81.2, 82.5. Anal. Calcd for C8H16O6 (%): C, 46.15; H, 7.75. Found: C, 46.09; H, 7.59.
10Analytical data: 1H NMR (400 MHz, CDCl3): δ = 2.06 (s, 3 H, COCH3), 2.08 (s, 6 H, 2 × COCH3), 2.13 (s, 3 H, COCH3), 3.44 (s, 3 H, O-CH3), 3.50 (s, 3 H, O-CH3), 3.62 (t, 1 H, J = 10.3 Hz, H-4), 3.64 (t, 1 H, J = 3.4 Hz, H-1), 5.14 (dd, 1 H, J = 10.3, 3.4 Hz, H-2), 5.21 (dd, 1 H, J = 10.3, 3.4 Hz, H-5), 5.43 (t, 1 H, J = 10.3 Hz, H-3), 5.51 (t, 1 H, J = 3.4 Hz, H-6). 13C NMR (100.4 MHz, CDCl3): δ = 20.8 (COCH3), 59.4 (O-CH3), 59.8 (O-CH3), 67.6, 70.5, 71.1, 76.6, 78.5, 169.5 (O-COCH3), 169.6 (O-COCH3), 169.8 (O-COCH3), 170.3 (O-COCH3).
13Analytical data: 1H NMR (400 MHz, CDCl3): δ = 1.93 (s, 3 H, COCH3), 2.01 (s, 3 H, COCH3), 3.71 (t, 1 H, J = 3.9 Hz, H-1), 3.74-3.80 (2 × dd, 2 H, H-2 and H-5), 3.88 (t, 1 H, J = 9.8 Hz, H-3), 4.31-4.89 (m, 8 H, 4 × CH2), 5.31 (t, 1 H, J = 9.8 Hz, H-4), 5.35 (t, 1 H, J = 3.9 Hz, H-6), 7.20-7.40 (m, 20 H, Ph). 13C NMR (100.4 MHz, CDCl3): δ = 20.90 (COCH3), 20.95 (COCH3), 67.3, 71.9, 73.1, 73.3, 73.6, 74.6, 74.7, 75.5, 77.2, 79.4, 79.4, 127.5, 127.6, 127.7, 127.8, 127.83, 127.9, 127.90, 127.92, 128.3, 128.4, 128.43, 137.8, 137.9, 138.1, 138.6, 169.8 (OCOCH3), 170.02 (OCOCH3). Anal. Calcd for C38H40O8·0.5H2O (%): C, 72.02; H, 6.52. Found C, 72.01; H, 6.89.
14Analytical data: 1H NMR (400 MHz, D2O): δ = 3.28 (t, 1 H, J = 9.4 Hz, H-3), 3.48 (s, 3 H, OCH3), 3.60 (s, 3 H, OCH3), 3.63 (t, 1 H, J = 9.6 Hz, H-4), 3.64 (t, 1 H, J = 3.6 Hz, H-1), 3.69 (dd, 1 H, J = 9.6, 3.6 Hz, H-5), 3.86 (dd, 1 H, J = 10.2, 3.6 Hz, H-2), 4.22 (t, 1 H, J = 3.6 Hz, H-6). 13C NMR (100.4 MHz, D2O, dioxane reference at 66.5 ppm): δ = 58.5, 59.8, 67.8, 70.6, 71.9, 81.5, 83.0. Anal. Calcd for C8H16O6·1.4H2O (%): C, 41.16; H, 8.12. Found: C, 41.08; H, 7.86.
15Analytical data: 1H NMR (400 MHz, CDCl3): δ = 1.99 (s, 3 H, COCH3), 2.08 (s, 3 H, COCH3), 2.14 (s, 6 H, 2 × COCH3), 3.47 (s, 3 H, OCH3), 3.49 (s, 3 H, OCH3), 3.68 (t, 1 H, J = 3.4 Hz, H-1), 3.68 (t, 1 H, J = 9.8 Hz, H-3), 5.12 (dd, 1 H, J = 10.3, 2.9 Hz, H-2), 5.20 (dd, 1 H, J = 10.3, 3.4 Hz, H-5), 5.34 (t, 1 H, J = 9.8 Hz, H-4), 5.49 (t, 1 H, J = 3.9 Hz, H-6). 13C NMR (100.4 MHz, CDCl3): δ = 20.65 (COCH3), 20.82 (COCH3), 20.86 (COCH3), 21.02 (COCH3), 59.32 (OCH3), 60.57 (OCH3), 67.24, 69.23, 71.26, 72.62, 76.55, 78.66, 169.73 (OCOCH3), 169.75 (OCOCH3), 170.04 (OCOCH3), 170.11 (OCOCH3). Anal. Calcd for C16H26O11 (%): C, 48.73; H, 6.65. Found: C, 48.46; H, 6.30.