Synthesis of 2-amino derivatives of levoglucosenone

Abstract

2-Amino derivatives of levoglucosenone were prepared by reaction of the 2-methanesulfonyl (or p-toluenesulfonyl) derivatives with ammonia, methylamine, or octylamine under various conditions. The analogous reaction did not occur for saturated derivative 15. The 2-amino-3,4-dihydro derivative was prepared by catalytic hydrogenation of unsaturated amine 9.Amino sugars act as structural components of many natural compounds including such large groups as mucopolysaccharides and mixed biopolymers. However, they are rarely found in the free state. As a rule, amino sugars required for organic synthesis are obtained by aminolysis of halides, sulfonates, and anhydro derivatives of monosaccharides or reduction of ketose oximes and hydrazones [1,2]. The carbohydrate levoglucosenone (1), which is prepared by cellulose pyrolysis [3], is promising for preparing unsaturated amino sugars and their derivatives. N-Containing derivatives of this sugar enone include heterocyclic products of tandem conversions [4-7], oxime 2 [8], and regioisomeric amines formed by hydroxyamination of 1,6-anhydro-3,4-dideoxy-β-D-threo-hex-3-enopyranose [9].Oxime 2 was synthesized by the literature method [8]. Furthermore, reaction of levoglucosenone with hydrazine sulfate in pyridine produced a different azomethine, hydrazone 3. Unfortunately, attempts to reduce azomethines 2 and 3 with LiAlH 4 gave products that were difficult to isolate from aqueous solutions.Alernative approaches could be based on substitution reactions, which are known to proceed difficultly in six-membered pyranose rings [1]. Nevertheless, keeping in mind the allylic position of the reaction center and the pseudoequatorial orientation of the substituted group, we studied the possibility of this approach.

Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (CyreneTM)

“…Remarkably, growing from the carbonyl group with standard functional groups has seen extremely little precedent in the literature, as judged from a search with the Reaxys search engine (June 2022, see Supplementary Materials Table S1 ). This scarcity is most evident for growing with a nitrogen-based substituent, for which only two compounds are known (–NH 2 and –N 3 ) [ 46 , 47 , 48 ]. We employed a modular strategy that allowed the assembly of a Cyrene-derived fragment library by reductive replacement of the carbonyl moiety with oxygen- but mostly nitrogen-based functional groups, many of which have a prominent position in FBDD and medicinal chemistry at large ( Figure 1 ).…”

Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene

“…of 24 : 1 (entry 7), 19 effectively yielding 3a in a single step from Cyrene™ as opposed to the previously reported 4-step synthesis from Levogluocosenone. 20…”

Synthesis of levoglucosenone oxazoline derivative

“…2-Amino-2,3,4-trideoxy-1,6-anhydro-β β β β β-D-eritrohex-3-enopyranose (I) was obtained by method [1]. (-)-(2S,5R,6R)-6-Acetoxy-5-acetoxyamino-2-acetoxymethyl-5,6-dihydro-2H-pyran (II).…”

“…Colorless crystals, mp149-150°C, R f 0. 3 1 H and 13 C NMR spectra were registered on a spectrometer Bruker AM-300 at operating frequencies 300 ( 1 H) and 75.47 ( 13 C) MHz in CDCl 3 , otherwise the other solvents are indicated in each separate case. The melting points were measured on a Koeffler device of the type S 30A/G.…”

“…Yield 0.160 g (76%), mp 89-92°C, R f 0.5 (hexane-ethyl acetate, 1:1), [a] D 20 -81.8°( C 1.0, CHCl 3 ) 1. H NMR spectrum, δ, ppm: 2.10 s (3H, CH 3 ), 4.12 d.d (1H, CH 2 , J 11.8, 6.1 Hz), 4.25 d.d (1H, CH 2 , J 11.8, 3.8 Hz), 4.48 m (1H, H 3 ), 4.62 m (1H, H 6 ), 6.0 d.d (1H, H 5 , J 10.4, 1.8 Hz), 6.22 m (1H, H 4 ), 6.34 d (1H, H 1 , J 7.1 Hz), 7.42 m (3H, Ph), 7.98 m (2H, Ph).…”