exo-Imino to endo-Iminocyclitol Rearrangement. A General Route to Five-Membered Antiviral Azasugars

Abstract

A facile synthesis is reported for five-membered iminocyclitols which allows for variation in stereochemistry at all the chiral centers, diverse C1- and N-substitution, and the potential for a three-component combinatorial process. The key step is inversion at the C4 stereocenter (L-lyxo sugar --> D-ribono azasugar). The exo-imino to endo-iminocyclitol process was extended to the D-lyxo and the D- and L-hexose series. Some analogues were found to be more potent than N-butyl DNJ and N-nonyl DNJ in antiviral activity.

Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose ring

“…The precursor 1-methyliminocyclitol 39 was prepared by the Moriarty rearrangement 47 of the exo -imino to endo -iminocyclitol, which involves inversion at C4 of the L-lyxo sugar to give the D-ribo azasugar. The imine 39 47 was mesylated at the primary alcohol to give 40 (85%), which was coupled with protected L-Hcy to give 41 (Scheme 5, 85%). Treatment of 41 with TFA for a short time gave only isopropylidene protected 42 .…”

“…Treatment of 39 47 (48.5 mg, 0.26 mmol) with MsCl (0.031 mL, 45 mg, 0.39 mmol) in the presence of Et 3 N (0.11 mL, 80 mg, 0.79 mmol) by Procedure A [3h; column chromatography (EtOAc → 10% MeOH/EtOAc)] gave 40 (59 mg, 85%) as a colorless oil: 1 H NMR δ 1.38 (s, 3), 1.39 (s, 3), 2.16 (d, J = 1.0 Hz, 3, N=CCH 3 ), 3.00 (s, 3, Ms), 4.38 (s, 1, H4), 4.39 (dd, 1, J = 3.6, 11.2 Hz, 1, H5), 4.53 (dd, J = 4.2, 11.3 Hz, 1, H5′), 4.64 (d, J = 5.8 Hz, 1, H3), 4.95 (‘quin’, J = 5.6 Hz, 1, H2); 13 C NMR δ 17.1 (N=C Me ), 25.7 (C Me 2 ), 26.8 (C Me 2 ), 37.4 (Ms), 69.7 (C5), 75.0 (C4), 79.8 (C3), 87.4 (C2), 112.4 ( C Me 2 ), 177.0 (C=N); MS (APCI) m/z 264 (100, MH + ).…”

Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles

“…NMR and IR data are in accordance with those of its enantiomer. 22 (2R,3S,4R,5S)-N-tert-Butoxycarbonyl-2-formyl-3,4-O-isopropylidene-5-methylpyrrolidine-3,4-diol (10). To a solution of 9 (50.7 mg, 0.176 mmol) in CH 2 Cl 2 (3 mL), Dess-Martin reagent (112 mg, 0.26 mmol) was added.…”

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

“…A unique synthetic sequence that is somewhat related to the one described by Behr (Scheme 78) has been reported by Moriarty et al 121 as a means to generate pyrrolidine iminosugars carrying various alkyl chains at C-1. The sequence involves the low-temperature addition of a Grignard reagent to an aldono-1,4-lactone carrying a leaving group at the C-d position, followed by the conversion of the resulting hemiketal into a glycosylamine (Scheme 80).…”