Establishment of the Structure of Pinpollitol by Total Synthesis of the Proposed Putative Structures

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

References

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7

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: [phone], e-mail: [e-mail]].

8

Analytical 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).

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Analytical 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.

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Analytical 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).

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Analytical 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.

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Analytical 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.

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Analytical 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.