An Expeditious Route Towards Pyranopyran Sugar Amino Acids

Gijsbert M. Grotenbreg; Adriaan W. Tuin; Martin D. Witte; Michiel A. Leeuwenburgh; Jacques H. van Boom; Gijsbert A. van der Marel; Herman S. Overkleeft; Mark Overhand

doi:10.1055/s-2004-820021

LETTER

An Expeditious Route Towards Pyranopyran Sugar Amino Acids

Gijsbert M. Grotenbreg, Adriaan W. Tuin, Martin D. Witte, Michiel A. Leeuwenburgh, Jacques H. van Boom, Gijsbert A. van der Marel, Herman S. Overkleeft*, Mark Overhand*
Leiden Institute of Chemistry, Gorlaeus Laboratories, P. O. Box 9502, 2300 RA Leiden, The Netherlands
Fax: +31(71)5274307; e-Mail: overhand@chem.leidenuniv.nl;

Abstract

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Abstract

The synthesis of two diastereoisomeric pyranopyran sugar amino acids, starting from (+)-d-3,4,6-tri-O-benzylglucal, is described. The key reaction sequence towards the bicyclic structure entails Petasis olefination followed by ring closing metathesis.

Key words

amino acids - bicyclic compounds - carbohydrates - pyranopyran - ring-closing metathesis

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References

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Reduction with sodium borohydride gave a diastereo-isomeric mixture of alcohols 9; endo:exo = 9:1, as judged by ¹H NMR analysis.

Physical Data for SAA 16: ¹H NMR (400 MHz, D₂O): δ = 4.49 (m, 1 H, H₆), 4.09 (d, 1 H, H₈, J _8,9 = 5.3 Hz), 4.05 (dd, 1 H, H₁₀, J _10,9 = 5.5 Hz, J _10,1 = 5.9 Hz), 4.02 (m, 2 H, H_3ax, H₄), 3.89 (dd, 1 H, H₉, J _9,8 = 5.3 Hz, J _9,10 = 5.5 Hz), 3.65 (dd, 1 H, H₁, J _1,6 = 3.5 Hz, J _1,10 = 5.9 Hz), 3.45 (ddd, 1 H, H_3eq, J _3eq,5eq = 1.7 Hz, J _3eq,4 = 7.8 Hz, J _3eq,3ax = 12.4 Hz), 2.37 (m, 1 H, H_5ax), 1.86 (m, 1 H, H_5eq). ¹³C NMR (100 MHz, D₂O): δ = 177.3 (C=O), 76.8 (C₈) 75.2 (C₁), 70.9 (C₉), 67.6 (C₁₀), 66.7 (C₃), 66.0 (C₆), 54.9 (C₄), 30.7 (C₅). ATR-IR (thin film): ν = 3398.1, 2920.0, 2120.1, 1605.6, 1454.5, 1385.0, 1315.5, 1247.7, 1096.9, 1076.7, 1062.2, 1001.4, 947.7, 923.1, 879.9, 811.4 cm^-1. MS (ESI): m/z = 260.0 [M + H]⁺, 282.1 [M + Na]⁺, 541.1 [2 M + Na]⁺.

Physical Data for SAA 17: ¹H NMR (400 MHz, D₂O): δ = 4.31 (m, 1 H, H₆), 4.10 (d, 1 H, H₈, J _8,9 = 5.8 Hz), 4.07 (dd, 1 H, H₁₀, J _10,9 = 6.1 Hz, J _10,1 = 6.3 Hz), 3.83 (dd, 1 H, H₉, J _9,8 = 5.8 Hz, J _9,10 = 6.1 Hz), 3.78 (m, 3 H, H₃, H₄), 3.70 (dd, 1 H, H₁, J _1,6 = 3.8 Hz, J _1,10 = 6.3 Hz), 2.15 (m, 2 H, H₅). ¹³C NMR (100 MHz, D₂O): δ = 177.4 (C=O), 76.7 (C₈) 75.6 (C₁), 71.5 (C₉), 68.2 (C₁₀), 66.8 (C₃, C₆), 55.2 (C₄), 30.3 (C₅). ATR-IR (thin film): ν = 3353.3, 2955.6, 2955.6, 2924.6, 2853.7, 2102.1, 1606.7, 1370.7, 1271.5, 1246.9, 1116.3, 1077.8, 1008.8. 967.4, 941.3 cm^-1 MS (ESI): m/z = 260.0 [M + H]⁺, 282.1 [M + Na]⁺.