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Synlett 2006(12): 1875-1878  
DOI: 10.1055/s-2006-948177
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of Sugar Iminopyrrolidine Derivatives via an Intramolecular Staudinger-aza-Wittig-Type Reaction

Hélène Ducatela, Albert Nguyen Van Nhiena, Serge Pilardb, Denis Postel*a
a Laboratoire des Glucides (UMR 6219), Faculté des Sciences, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France
Fax: +33(3)22827568; e-Mail: denis.postel@u-picardie.fr;
b Plateforme Analytique, Université de Picardie Jules Verne, Faculté des Sciences, 33, rue Saint Leu, 80039 Amiens, France
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Publication History

Received 16 March 2006
Publication Date:
24 July 2006 (online)

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Abstract

We report herein the first example of a Staudinger-aza-Wittig-type reaction on a substituted furanoside in which a β-azido glyco-α-aminonitrile was converted into fused iminopyrrolidines in good yields, and the following hydrolysis gave the corresponding conformationally restricted glycoamino acids.

Key words

aza-sugars - Wittig reactions - glycoamino nitrile - ­glycoamino acids - iNOS

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(1 R ,3 R ,4 R ,5 R )-5,6-Diamino-3,4- O -isopropylidene-7-aza-2-oxabicyclo[3.3.0]oct-6-ene ( 8).
To a solution of compound 2 (0.20 g, 0.85 mmol) in 10 mL of THF-H2O (4:1) was added 0.25 g (0.93 mmol) of PPh3. After stirring overnight at r.t., the reaction mixture was evaporated and extracted with Et2O and H2O. The aqueous layer was evaporated to give 0.16 g (89%) of 8 as a slight yellow syrup; [α]D 20 20 (c 0.17, CHCl3). IR (ATR): 2988, 1655, 1374, 1217, 1165, 1086, 1007, 877, 733 cm-1. 1H NMR (CDCl3): δ = 5.80 (d, 1 H, H-1, J 1,2 = 3.9 Hz), 4.60 (d, 1 H, H-2), 4.30 (d, 1 H, H-4, J 4,5a = 3.0 Hz), 3.72 (dd, 1 H, H-5a, J 5a,5b = 14.0 Hz), 3.67 (d, 1 H, H-5b), 1.53 (s, 3 H, CH3), 1.35 (s, 3 H, CH3). 13C NMR (CDCl3): δ = 168.2 (C=N), 112.9 (CH3 CCH3), 106.1 (C-1), 85.1 (C-4), 82.2 (C-2), 74.1 (C-3), 55.5 (C-5), 27.6, 27.3 (2 × CH3). HRMS: m/z calcd for C9H16N3O3 [M + H]+: 214.1192; found: 214.1196. Anal. Calcd for C9H15N3O3: C, 50.69; H, 7.09; N, 19.71. Found: C, 50.54; H, 6.95; N, 19.60.

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Key Data for Compound 9. 13C NMR (CDCl3): δ = 173.4 (C=N, J 2 C-P = 9.0 Hz), 75.4 (C-3, J 3 C-P = 17.2 Hz), 14.4 [P(CH3)3, J 1 CH3-P = 66.0 Hz). MS: m/z = 288.14 [M + H]+.

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3-Amino-3-deoxy-1,2- O -isopropylidene-α- d-ribofurano-sidurono-3,5-lactam ( 17).
White solid, mp 159-162 °C; [α]D 20 18 (c 0.11, CHCl3). 1H NMR (CD3OD): δ = 5.81 (d, 1 H, H-1, J 1,2 = 3.9 Hz), 4.60 (d, 1 H, H-2), 4.40 (d, 1 H, H-4, J 4,5a = 3.5 Hz), 3.65 (dd, 1 H, H-5a, J 5a,5b = 11.8 Hz), 3.32 (d, 1 H, H-5b), 1.56 (s, 3 H, CH3), 1.38 (s, 3 H, CH3). 13C NMR (CD3OD): δ = 176.4 (1 C, C=O), 112.8 (1 C, CH3 CCH3), 106.1 (1 C, C-1), 81.9 (1 C, C-2), 81.8 (1 C, C-4), 68.8 (1 C, C-3), 45.6 (1 C, C-5), 26.4, 26.0 (2 C, CH3). IR (ATR): ν = 2959, 2932, 1716, 1659, 1465, 1382, 1233, 1166, 1098, 1082, 1001 cm-1. HRMS: m/z calcd for C9H14N2O4Na: 237.0851 [M + Na]+; found: 237.0850.

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3,5-Diamino-3- C -carboxy-3,5-dideoxy-1,2- O -isopropyl-idene-α- d-ribofuranose ( 18). White solid, mp 200 °C; [α]D 20 77 (c 0.21, H2O). 1H NMR (D2O): δ = 5.88 (d, 1 H, H-1, J 1,2 = 3.6 Hz), 4.55 (d, 1 H, H-2), 3.94 (dd, 1 H, H-4, J 4,5a = 1.8 Hz), 3.13 (dd, 1 H, H-5a, J 5a,5b = 13.3 Hz), 2.78 (dd, 1 H, H-5b, J 5b,4 = 9.9 Hz), 1.44 (s, 3 H, CH3), 1.27 (s, 3 H, CH3). 13C NMR (D2O): δ = 175.1 (1 C, C=O), 113.4 (1 C, CH3 CCH3), 105.9 (1 C, C-1), 83.3 (1 C, C-2), 80.3 (1 C, C-4), 68.5 (1 C, C-3), 40.1 (1 C, C-5), 26.1, 25.7 (2 C, CH3). IR (ATR): ν = 2987, 2917, 1614, 1540, 1409, 1381, 1230, 1163, 1069, 1015, 883, 809 cm-1. HRMS: m/z calcd for C9H16N2O5Na: 255.0957 [M + Na]+; found: 255.0950.

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(1 R ,3 R ,4 R ,5 R )-5-{[1,2- O -Isopropylidene-α- d-xylo-furanos-5-yl]amino}-6-amino-3,4- O -isopropylidene-7-aza-2-oxabicyclo[3.3.0]oct-6-ene ( 21).
White solid, mp 125-128 °C; [α]D 20 18.2 (c 0.36, CHCl3). IR (ATR): 2989, 2901, 1655, 1384, 1217, 1167, 1073, 1014, 879, 858 cm-1. 1H NMR (CDCl3): δ = 5.89 (d, 1 H, H-1, J 1,2 = 3.6 Hz), 5.77 (d, 1 H, H-1′, J 1 ′ ,2 ′ = 3.7 Hz), 4.62 (d, 1 H, H-2′), 4.52 (s, 1 H, H-4), 4.38 (d, 1 H, H-2), 4.14 (d, 1 H, H-4′, J 4 ′ ,3 ′ = 2.7 Hz), 4.05 (d, 1 H, H-3′), 3.56 (s, 2 H, H-5′), 3.06 (d, 1 H, H-5a, J 5a,5b = 11.7 Hz), 2.77 (dd, 1 H, H-5b, J 5b,4 = 3.5 Hz), 1.48 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 1.29 (s, 3 H, CH3), 1.20 (s, 3 H, CH3). 13C NMR (CDCl3): δ = 164.9 (1 C, CN), 112.9, 111.5 (2 C, CH3 CCH3), 105.2, 104.8 (2 C, 2 C-1), 85.6 (1 C, C-2), 83.1 (1 C, C-4), 82.2 (1 C, C-2′), 77.9 (1 C, C-4′), 76.5 (2 C, C-3′, C-3), 58.2 (1 C, C-5′), 42.4 (1 C, C-5), 27.3 (1 C, CH3), 27.1 (1 C, CH3), 26.7 (1 C, CH3), 26.1 (1 C, CH3). HRMS: m/z calcd for C17H28N3O7: 386.1927 [M + H]+; found: 386.1908. Anal. Calcd for C17H27N3O7: C, 52.98; H, 7.06; N, 10.90. Found: C, 52.91; H, 7.04; N, 10.87.

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3,5-Diamino-3- C -carboxy-3,5-dideoxy-3- N -[1′,2′- O -isopropylidene-α- d-xylofuranos-5′-yl]-1,2- O -isopropyl-idene-α- d-ribofuranose ( 22).
White solid, mp 254-256 °C; [α]D 25 8.0 (c 0.21, CHCl3). IR (ATR): 2987, 2900, 1589, 1394, 1215, 1066 cm-1. 1H NMR (CD3OD): δ = 5.99 (d, 1 H, H-1′, J 1 ′ ,2 ′ = 3.6 Hz), 5.95 (d, 1 H, H-1, J 1,2 = 3.8 Hz), 5.01 (d, 1 H, H-2), 4.49 (d, 1 H, H-2′), 4,22 (m, 2 H, H-4′, H-3′), 3.98 (t, 1 H, H-4, J 4,5 = 6.8 Hz), 3.12 (d, 2 H, H-5), 3.56 (dd, 2 H, H-5a′, J 5a,5b = 11.7 Hz, J 5a,4 = 6.3 Hz), 2.71 (dd, 1 H, H-5b′, J 5b,4 = 7.3 Hz), 1.56 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 1.31 (s, 3 H, CH3). 13C NMR (CD3OD): δ = 174.6 (1 C, C=O), 112.3, 111.6 (2 C, CH3 CCH3), 106.8, 105.4 (2 C, C-1′, C-1), 85.2 (1 C, C-2′), 81.2 (1 C, C-2), 80.8 (1 C, C-4′), 77.8 (1 C, C-4), 76.5 (2 C, C-3′, C-3), 43.1 (1 C, C-5′), 40.9 (1 C, C-5), 26.4 (1 C, CH3), 26.2 (1 C, CH3), 25.7 (1 C, CH3), 25.5 (1 C, CH3). HRMS: m/z calcd for C17H28N2O9Na: 427.1693
[M + Na]+; found: 427.1685.