Synthesis of 4-Carbamoyl-2-oxazolidinones C-4-Linked with a Saccharide Moiety via Bucherer-Bergs Reaction of Hexofuranos-5-uloses

Abstract

Application of the Bucherer-Bergs reaction to 6-O-unprotected hexofuranos-5-uloses led to the formation of 4-carbamoyl-2-oxazolidinones C-4-linked with a carbohydrate moiety instead of expected carbohydrate-C-5-linked hydantoin (imidazolidin-2,4-dione) derivatives. Starting from hexofuranos-5-uloses having all hydroxyl groups suitably protected, only corresponding saccharide-linked hydandoins were obtained.

Key words

carbohydrates - 5-membered heterocycles - conjugation - Bucherer-Bergs reaction - 5-hexofuranos-5-uloses

References

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6

Recently, we have prepared both 5-(R)- and 5-(S)-hydantoins 11 and 12 by selective detritylation of 5 and 6, respectively. These were fully characterized by ¹H and
¹³C NMR and mass spectral data and at present, they are subjected to X-ray analysis to determine the configuration at C-5.

12

In a typical experimental procedure, a mixture of 5-ulose 3 (10 mmol), KCN (20 mmol), and (NH₄)₂CO₃ in 50% aq EtOH (20 mL) was stirred at 60 °C for 8 h. Ethanol was then evaporated and the product extracted with CHCl₃. After complete solvent removal in vacuo, the residue was chromatographed on a column of silica gel using 8:1 (v/v) CHCl₃-MeOH as an eluent. This afforded 4 (43% yield) which was crystallized from EtOAc: mp 235-237 °C; [α]_D +58 (c 1, MeOH); ¹H NMR (300 MHz, CDCl₃): δ = 6.80
(br s, 1 H, NH), 6.09 (br s, 1 H, NH), 5.67 (br s, 1 H, NH), 4.98 (s, 1 H, H-1), 4.82 (dd, 1 H, J _2,3 = 5.9 Hz, J _3,4 = 3.4 Hz, H-3), 4.57 (d, 1 H, J _{5 ′ a,5 ′ b} = 7.1 Hz, H-5′a), 4.56 (d, 1 H, H-2), 4.46 (d, 1 H, H-5′b), 4.45 (d, 1 H, H-4), 3.35 (s, 3 H, OCH₃), 1.54 and 1.28 (2 s, each 3 H, Me₂C); ¹³C NMR (75.5 MHz, CDCl₃):
δ = 172.9 (CONH₂), 159.1 (NHCOO), 113.2 (CMe₂), 106.9 (C-1), 85.1 (C-2), 79.9 (C-3), 78.6 (C-4), 72.6 (C-5′), 64.0 (C-4′ = C-5), 55.0 (OCH₃), 25.8 and 23.9 [(CH₃)₂C] (data for the 2-oxazolidinone moiety are identified by a prime); MS (EI, 70 eV): m/z (%) = 287 [M - Me]⁺, 258 (100) [M - CONH₂]⁺, 226, 170, 134, 75, 40; CIMS: m/z 382 [M + 80]⁺. Anal. Calcd for C₁₂H₁₈N₂O₇: C, 47.70; H, 6.00; N, 9.27. Found: C, 47.81; H, 6.08; N, 9.20. The 2-oxazolidinone derivatives 7-10 were prepared analogously (yield: 7, 38%; 8, 45%; 9, 41%; 10, 44%), starting from the corresponding 5-uloses.

14

Crystallographic data for 4 has been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 178704. Copies of this information may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: [phone]; e-mail: [e-mail]).