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Synlett 2005(10): 1547-1550  
DOI: 10.1055/s-2005-869846
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Divergent Synthesis of Uncommon Sugars from Furanaldehyde

Lizhi Zhu, Arindam Talukdar, Guisheng Zhang, James P. Kedenburg, Peng George Wang*
Department of Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
Fax: +1(614)6883106; e-Mail: wang.892@osu.edu;
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Publication History

Received 28 February 2005
Publication Date:
12 May 2005 (online)

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Abstract

A practical synthetic strategy has been developed for producing uncommon sugars. This method employed kinetic enzymatic resolution of 1-(2-furyl)ethanol, and followed by NBS-mediated Achmatowicz rearrangement to construct α,β-unsaturated lactones. After further derivatization, five representative uncommon sugar units were successfully synthesized.

Key words

uncommon sugar - enzymatic kinetic resolution - 1-(2-furyl)ethanol - Achmatowicz rearrangement

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Compound 4 is not very stable, after reaction it should be used directly. Storage at 4 °C for 3 d led to decomposition to a black oil.

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Procedure for Kinetic Enzymatic Resolution of ( R )-1-(2-Furyl)ethanol.
To a stirred mixture of 1-(2-furyl)ethanol (60 g, 0.54 mol) and isopropenyl acetate (200 mL, 1.82 mol) in diisopropyl ether (200 mL) was added Novozyme 435 (3.0 g). The reaction mixture was warmed to 40 °C and monitored by GC analysis. The reaction was stopped by filtration when 45% conversion rate was reached (ca. 2.5 h). The filtrate was concentrated on rotary evaporator. The residue was subjected for fractional distillation and collected the fraction at 82-85 °C/25 mmHg. The yellow oil obtained was consequently mixed with PBS buffer (pH = 7.0, 1.2 L) and Novozyme 435 (2.0 g) and stirred at r.t. for 2 h. TLC indicated the completion of the hydrolysis. The enzyme was removed by filtration and the aqueous solution was extracted with EtOAc (6 × 150 mL). The combined organic phases were dried over MgSO4 and concentrated under vacuum. The crude product was purified by column chromatography (hexanes-EtOAc, 10:1) to give (R)-1 (21.5 g, >97% ee by chiral GC analysis).

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Spectroscopic data.
Compound 9 was obtained as its α-anomer from the coupling constant of the anomeric proton signal. The parent ion was not observed by HRMS, due to decomposition of this compound under the analysis conditions. IR (neat): 2950, 2100 (N3 group), 1275, 1050 cm-1. 1H NMR (250 MHz, CDCl3): δ = 4.96 (d, J = 3.0 Hz, 1 H), 4.09 (qd, J = 6.5, 1.8 Hz, 1 H), 3.91 (sept, J = 6.1 Hz, 1 H), 3.48 (m, 1 H), 2.14 (m, 1 H), 1.95 (m, 2 H), 1.56 (m, 1 H), 1.22 (d, J = 6.5 Hz, 6 H), 1.16 (d, J = 6.1 Hz, 3 H). 13C NMR (63 MHz, CDCl3): δ = 94.2, 67.9, 64.8, 59.8, 24.3, 23.0, 22.7, 21.2, 17.6.
Compound 10: 1H NMR (400 MHz, CD3OD): δ = 4.37-4.32 (m, 1 H), 3.86 (d, J = 9.0 Hz, 1 H), 3.67 (d, J = 4.2 Hz, 1 H), 3.62 (d, J = 4.2 Hz, 1 H), 1.34 (d, J = 6.3 Hz, 3 H). 13C NMR (100 MHz, CD3OD): δ = 167.6, 73.4, 71.1, 55.9, 50.5, 17.1. HRMS (ESI): m/z calcd for C6H8O4Na: 167.0320 [M + Na+]. Found: 167.0324.
Compound 13: 1H NMR (400 MHz, CD3OD): δ = 4.48-4.42 (m, 1 H), 3.92 (d, J = 9.2 Hz, 1 H), 3.63 (d, J = 4.4 Hz, 1 H), 3.54 (d, J = 4.4 Hz, 1 H), 1.33 (d, J = 6.4 Hz, 3 H), 0.93 (s, 9 H), 0.18 (s, 3 H), 0.15 (s, 3 H).
13C NMR (100 MHz, CD3OD): δ = 166.7, 73.3, 71.0, 55.9, 50.7, 25.8, 18.3, -3.9, -4.5. HRMS (ESI): m/z calcd for C12H22O4SiNa: 281.1185 [M + Na+]. Found: 281.1190.
Compound 17 was obtained as a mixture of α/β-anomers, selected data for β-anomer: 1H NMR (400 MHz, CD3OD): δ = 5.03 (dd, J = 9.0, 2.3 Hz, 1 H), 4.10 (q, J = 3.5 Hz, 1 H), 3.64 (dq, J = 9.2, 6.3 Hz, 1 H), 3.41 (m, 1 H), 2.14 (q, J = 14.0 Hz, 1 H), 1.83 (m, 1 H), 1.32 (d, J = 6.7 Hz, 3 H). 13C NMR (100 MHz, CD3OD): δ = 90.8, 69.7, 67.0, 63.1, 32.1, 15.3. [α]D 25 38 (c 1.0, MeOH-d 4). HRMS (EI): m/z calcd for C6H11N3O3: 173.0796. Found: 173.0802.