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Synlett 2004(11): 1945-1948  
DOI: 10.1055/s-2004-830886
LETTER
© Georg Thieme Verlag Stuttgart · New York

Selective Formation of 1,3-Oxazolidine-2-thiones on Ketohexose Templates

Arnaud Tatibouët*a, Scott Lawrenceb, Patrick Rollina, Geoffrey D. Holmanb
a ICOA - UMR 6005, Université d’Orléans, BP 6759, 45067 Orléans, France
Fax: +33(2)38417281; e-Mail: arnaud.tatibouet@univ-orleans.fr;
b Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
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Publication History

Received 18 May 2004
Publication Date:
04 August 2004 (online)

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Abstract

Thiocyanic acid condensation on selectively protected ketohexose led to the isolation of five out of the seven possible 1,3-oxazolidine-2-thiones (OZT). The four isomeric spiro-OZT synthesized showed promising biological activity against d-fructose transport.

Key words

carbohydrates - bicyclic compounds - spiro compounds - d-fructose - 1,3-oxazolidine-2-thione

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General Protocol for the Formation of 23 and 24: 1,2-O-Isopropylidene-3,4-di-O-benzyl-β-d-fructopyranose 20 (1.1 g, 2.75 mmol) was dissolved in a cooled solution of TFA-H2O (3:2) and stirred at r.t. overnight. The crude solution was evaporated and co-evaporated with toluene (3 times); the residue was suspended in H2O containing KSCN (670 mg, 6.87 mmol) and 37% HCl (0.57 mL) was added. The resulting solution was heated for 3 d at 50 °C, then cooled and extracted with EtOAc (3 times). The organic phases were collected and washed with NaHCO3 until neutral, then with brine and dried over MgSO4. The residue obtained after evaporation was purified on column chromatography using petroleum ether-EtOAc (1:1 mixture). Spiro-furano OZT 22 (410 mg, 1.02 mmol, 37% yield) was isolated as the first fraction then spiro-pyrano OZT 21 (250 mg, 0.62 mmol, 22% yield). Each fraction was acetylated (Ac2O 2 mL, pyridine 5 mL, 24 h); after co-evaporation with toluene, the residue was purified on column chromatography using petroleum ether-EtOAc mixtures (8:2 for furano OZT and 7:3 for pyrano OZT). Spiro-furano OZT 23α (155 mg, 0.32 mmol, 37% yield) and then 23β (150 mg, 0.31 mmol, 35% yield) was isolated. Spiro-furano OZT 23α: [α]D 25 +134.0 (c 1.0, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 1.99 (s, 3 H, OAc), 2.70 (s, 3 H, NAc), 3.86 (dd, 1 H, J 3,4 = 8.0 Hz, J 4,5 = 9.1 Hz, H-4), 3.95 (dd, 1 H, J 5,6b = 4.4 Hz, J 6a,6b = 12.5 Hz, H-6b), 4.14 (d, 1 H, J 1a,1b = 10.0 Hz, H-1b), 4.22 (dd, 1 H, J 5,6a = 2.3 Hz, H-6a), 4.46 (ddd, 1 H, H-5), 4.50 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.63 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.63 (d, 1 H, J = 11.7 Hz, CH2Ph), 4.73 (d, 1 H, J = 11.7 Hz, CH2Ph), 4.94 (d, 1 H, H-1a), 5.09 (d, 1 H, H-3), 7.23-7.38 (m, 10 H, H-Ar). 13C NMR (62.5 MHz, CDCl3): δ = 20.7 (OAc), 28.0 (NAc), 62.9 (C-6), 72.9 (CH2Ph), 73.6 (C-1), 74.0 (CH2Ph), 78.0 (C-5), 80.9 (C-4), 83.3 (C-3), 100.5 (C-2), 127.9, 128.2, 128.4, 128.6, 128.7, 128.9, 136.6, 137.4 (C-Ar), 170.4 (CO), 172.1 (CO), 185.7 (CS). MS (IS+): m/z = 508.0 [M + Na]+, 486 [M + H]+, 466.0 [M - Ac + Na]+. Anal. Calcd for C25H27NO7S: C, 61.84; H, 5.61; N, 2.89. Found: C, 61.61; H, 5.59; N, 2.88. Spiro-furano OZT 23β: [α]D 25 +7.0 (c 1.2, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 2.07 (s, 3 H, OAc), 2.75 (s, 3 H, NAc), 4.05 (d, 1 H, J 1a,1b = 10.1 Hz, H-1b), 4.11 (ddd, 1 H, J 4,5 = 7.5 Hz, J 5,6a = 3.4 Hz, J 5,6b = 7.6 Hz, H-5), 4.20 (d, 1 H, J 3,4 = 6.5 Hz, H-3), 4.31 (dd, 1 H, J 6a,6b = 11.8 Hz, H-6b), 4.41 (d, 1 H, H-1a), 4.43 (dd, 1 H, H-6a), 4.53 (dd, 1 H, H-4), 4.55 (d, 1 H, J = 11.7 Hz, CH2Ph), 4.60 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.66 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.68 (d, 1 H, J = 11.7 Hz, CH2Ph), 7.21-7.40 (m, 10 H, H-Ar). 13C NMR (62.5 MHz, CDCl3): δ = 21.0 (OAc), 27.6 (NAc), 65.1 (C-6), 73.2 (CH2Ph), 73.6 (CH2Ph), 77.6 (C-1), 80.9 (C-5), 84.2 (C-4), 87.1 (C-3), 99.5 (C-2), 127.8, 128.2, 128.3, 128.7, 128.9, 136.6, 137.5 (C-Ar), 171.0 (CO), 172.7 (CO), 186.4 (CS). MS (IS+): m/z = 508.0 [M + Na]+, 466.0 [M - Ac + Na]+. Anal. Calcd for C25H27NO7S: C, 61.84; H, 5.61; N, 2.89. Found: C, 61.48; H, 5.81; N, 2.63.
Spiro-pyrano OZT 24β (50 mg, 0.10 mmol, 27% yield) and then 24α (75 mg, 0.15 mmol, 41% yield) were also isolated. Spiro-pyrano OZT 24β: [α]D 25 -98 (c 1.0, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 2.12 (OAc), 2.68 (NAc), 3.76 (d, 1 H, J 3,4 = 8.8 Hz, H-3), 3.90 (dd, 1 H, J 5,6b = 2.6 Hz, J 6a,6b = 12.7 Hz, H-6b), 4.06 (d, 1 H, J 1a,1b = 9.6 Hz, H-1b), 4.38 (d, 1 H, H-1a), 4.41 (dd, 1 H, J 5,6a = 1.3 Hz, H-6a), 4.42 (dd, 1 H, J 4,5 = 3.9 Hz, H-4), 4.49 (d, 1 H, J = 10.6 Hz, CH2Ph), 4.60 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.69 (d, 1 H, J = 10.6 Hz, CH2Ph), 4.92 (d, 1 H, J = 10.6 Hz, CH2Ph), 5.51 (m, 1 H, H-5), 7.16-7.37 (m, 10 H, H-Ar). 13C NMR (62.5 MHz, CDCl3): δ = 21.2 (OAc), 28.0 (NAc), 66.1 (C-6), 67.3 (C-5), 71.8 (CH2Ph), 75.6 (C-3), 77.1 (C-4), 78.5 (C-1), 97.7 (C-2), 127.8, 128.1, 128.3, 128.6, 128.7, 137.3, 137.5 (C-Ar), 170.4 (CO), 174.7 (CO), 187.9 (CS). MS (IS+): m/z = 508.0 [M + Na]+, 466.0 [M - Ac + Na]+, 444.0 [M - Ac + H]+. Anal. Calcd for C25H27NO7S: C, 61.84; H, 5.61; N, 2.89. Found: C, 61.68; H, 5.48; N, 2.85. Spiro-pyrano OZT 24α: [α]D 25 +45.0 (c 1.2, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 2.23 (s, 3 H, OAc), 2.65 (s, 3 H, NAc), 3.45 (dd, 1 H, J 4,3 = 10.2 Hz, J 4,5 = 2.1 Hz, H-4), 3.57 (dd, 1 H, J 5,6b = 1.3 Hz, J 6a,6b = 14.0 Hz, H-6b), 4.04 (dd, 1 H, J 5,6a = 1.3 Hz, H-6a), 4.38 (d, 1 H, J 1a,1b = 9.3 Hz, H-1b), 4.54 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.59 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.73 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.76 (d, 1 H, H-1a), 4.85 (d, 1 H, J = 11.4 Hz, CH2Ph), 5.06 (d, 1 H, H-3), 5.34 (m, 1 H, H-5), 7.21-7.33 (m, 10 H, H-Ar). 13C NMR (62.5 MHz, CDCl3): δ = 21.2 (OAc), 28.1 (NAc), 64.0 (C-6), 66.9 (C-5), 70.6 (C-1), 72.0 (CH2Ph), 73.6 (C-3), 75.7 (CH2Ph), 78.2 (C-4), 97.3 (C-2), 127.9, 128.1, 128.2, 128.6, 137.3, 137.6 (C-Ar), 170.7 (CO), 172.0 (CO), 186.7 (CS). MS (IS+): m/z = 508.0 [M + Na]+, 466.0 [M - Ac + Na]+, 444.0 [M - Ac + H]+. Anal. Calcd for C25H27NO7S: C, 61.84; H, 5.60; N, 2.88. Found: C, 61.72; H, 5.57; N, 2.88.