An Expeditious Route Towards Pyranopyran Sugar Amino Acids

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

References

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7

A competing reaction occurred, resulting in the formation of significant quantities of trans-cyclopropane-1,2,3-tricarboxylic acid trimethyl ester. This side product was separated from the target compound 4 by size exclusion chromatography (Sephadex LH-20).

10

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

11

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]⁺.

12

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]⁺.