Synthesis of Novel Polyhydroxylated Tetrahydropyranopyrroles

Sébastien Naud; Muriel Pipelier; Christophe Chaumette; Guillaume Viault; François Huet; Stéphanie Legoupy; Didier Dubreuil

doi:10.1055/s-2007-968030

LETTER

Synthesis of Novel Polyhydroxylated Tetrahydropyranopyrroles

Sébastien Naud^a, Muriel Pipelier^a, Christophe Chaumette^a, Guillaume Viault^a, François Huet^b, Stéphanie Legoupy^b, Didier Dubreuil*^a
^a Université de Nantes, CNRS, Laboratoire de Synthèse Organique, UMR 6513, Faculté des Sciences et des Techniques, 2 Rue de la Houssinière, BP 92208 44322 Nantes Cedex 3, France
Fax: +33(2)51125402; e-Mail: didier.dubreuil@univ-nantes.fr;
^b Université du Maine, CNRS, Laboratoire de Synthèse Organique, UCO2M, UMR 6011, Faculté des Sciences et des Techniques, Avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France

Abstract

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Abstract

The stereoselective access to original polyhydroxylated tetrahydropyranopyrroles is described. The key steps involve an inverse-demand Diels-Alder reaction and a ring contraction of a pyridazine heterocycle.

Key words

pyrroles - pyridazines - α-pyrones - ring contractions - cycloadditions

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References

References and Notes

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17

Purification of 23 and 24 on silica gel is not recommended; otherwise, a mixture of cyclized and non-cyclized products could be obtained.

18

NMR Data of (4 R ,5 S ,1′ R ,2′ R )-3-Butyl-4-hydroxy-2-methoxycarbonyl-7-oxo-5-(1′,2′,3′-trihydroxyprop-1′-yl)-1,4,5,7-tetrahydropyrano[3,4- b ]pyrrole [(4 R )-26].
¹H NMR (400 MHz, CD₃OD): δ = 0.94 [t, 3 H, H_δ(Bu), ³ J = 7.3 Hz], 1.40 [m, 2 H, H_γ(Bu)], 1.50-1.67 [m, 2 H, H_β(Bu)], 2.85 [m, 2 H, H_α(Bu)], 3.74 (dd, 1 H, H₃ _′ _a, J ₃ _′ _a-3 _′ _b = 11.5 Hz, J ₃ _′ _a-2 _′ = 6.6 Hz), 3.83 (dd, 1 H, H₃ _′ _b, J ₃ _′ _b-3 _′ _a = 11.5 Hz, J ₃ _′ _b-2 _′ = 4.0 Hz), 3.87 (s, 3 H, OMe), 4.00 (m, 1 H, H₂ _′), 4.19 (dd, 1 H, H₁ _′, J ₁ _′ _-5 = 7.9 Hz, J ₁ _′ _-2 _′ = 4.6 Hz), 4.56 (dd, 1 H, H₅, J _5-1 _′ = 7.9 Hz, J _5-4 = 2.1 Hz), 5.00 (d, 1 H, H₄, J _4-5 = 2.1 Hz). ¹³C NMR (100 MHz, CD₃OD): δ = 4.2 [C_δ(Bu)], 23.7 [C_γ(Bu)], 25.3 [C_α(Bu)], 34.3 [C_β(Bu)], 52.1 (OMe), 60.7 (C₄), 63.9 (C₃ _′), 72.1 (C₁ _′), 73.8 (C₂ _′), 84.1 (C₅), 121.5, 126.2 (C₂, C₅), 130.8, 131.8 (C₃, C₄), 160.7, 162.5 (2 CO). HRMS: m/z calcd for C₁₆H₂₄NO₈ [M + H]⁺: 358.1502; found: 358.1490. [α]_D ²⁰ +21.2 (c 1.65, MeOH).