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Synlett 2004(5): 0904-0906  
DOI: 10.1055/s-2004-820021
LETTER
© Georg Thieme Verlag Stuttgart · New York

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;
Further Information

Publication History

Received 4 February 2004
Publication Date:
04 March 2004 (online)

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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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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, H3ax, 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, H3eq, J 3eq,5eq = 1.7 Hz, J 3eq,4 = 7.8 Hz, J 3eq,3ax = 12.4 Hz), 2.37 (m, 1 H, H5ax), 1.86 (m, 1 H, H5eq). 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]+.