Synthesis of azasugars by Grignard reaction on glycosylamines (original) (raw)
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European Journal of Organic Chemistry, 2007
A systematic synthetic strategy has been developed for producing uncommon piperidine 1,2-dideoxy-L-azasugars. This method involves the formation of open intermediates such as 2, 7, and 10 easily by ring-opening of D-glycals with aqueous mercury(II) acetate/sodium borohydride. A concise sequence of regioselective amination and cyclization reactions then allowed us to prepare the cyclic compounds 5a and 5b, L enantiomers of naturally occurring fagomine congeners such as 3-epi-fagomine (II) and 3,4-di-epi-fagomine (III), from Dglucal and D-galactal, respectively. The unnatural 3,4-di-epi-6-deoxyfagomine 9 was obtained from L-rhamnal by the [a] 1465 Scheme 5. Reagents and conditions: i) pyridine, Et 3 N, MeSO 2 Cl, room temp., 12 h, 90%; ii) THF, TBAF, room temp., 12 h, 74-80 %. ual procedure (90 %). After removal of the silyl-protecting group of 15a,b by reaction with TBAF in THF at room temp. (74-80 %), Et 3 N-promoted cyclization of 16a,b successfully gave 3,4,6-tri-O-benzyl-2-deoxy-1,5-anhydro-hexitols 17a,b in 75 % yield (Scheme 5).
Tetrahedron: Asymmetry, 2004
Bicyclic azasugar thioglycosides, a new type of azasugar and alkaloid derivative, are stereoselectively prepared from easily available glycosylenamines (D D -gluco and L L -rhamno configurations), via 1,4-anhydroazasugar derivatives. Polyhydroxylated pyrrolidines (nonreducing pyrrolidine azasugars) are also prepared by reduction with sodium cyanoborohydride of the same 1,4anhydroazasugars. The stereochemical assignments of the new stereogenic centres are based on NMR experiments, including a study of the interproton distances from quantitative treatment of NOE data and molecular modeling.
The Journal of Organic Chemistry, 1999
Nitrogen-in-the-ring "aza-sugars" have been synthesized in enantiomerically pure form from the amino acid L-alanine in excellent overall yield. The O'Donnell's Schiff base of L-alanine methyl ester 9a was converted to aza-sugar L-fuco-1-deoxy-nojirimycin, 18, and to the epimer L-gulo-1deoxy-nojirimycin, 20, in eight steps. The overall yields were 20 and 29%, respectively. The methodology for the efficient generation of silyl-and benzyl-protected (E)-3-lithio-2-propen-1-ols, and the use of these alkenyllithiums with iBu 5 Al 2 H as nucleophiles in the threo-selective tandem reduction-alkenylation of the Schiff base esters is described. Osmium-catalyzed cis-oxygenation of the resulting olefin products was selective for the galacto (fuco) amino polyols in all cases for the acyclic olefins, and was gulo-selective for the cyclic D-4,5-dihydropyridine pivalate, 17c. TEMPO-NaOCl was selective for oxidation of the primary position of the acyclic Schiff bases, and allowed for minimal protection/deprotection of the intermediates. The resulting N-benzhydryl heterocycles were easily deprotected with H 2-Pd at atmospheric pressure.
Angewandte Chemie International Edition, 2003
Although amine nitrogen atoms are potential stereogenic centers, their configurational lability arising from lone-pair inversion [1] has typically prevented their utility in synthesis. N-Halogenation can dramatically slow lone-pair inversion [2] and therefore raise the temperature at which the configurational lability ceases. We therefore considered that if a suitable system could be found, N-chloramines might provide a new source of flexible, temperature-dependent stereogenesis. In turn, existing chiral information may then be relayed and exploited such that subsequent reactions are regio-or diastereoselective. Due to the often higher conformational lability of the acyclic N lone-pair isomers of N-haloamines, we selected cyclic amines for our study, which are typically, but not always, less labile due to angular constraint. [1] Cyclic systems have often been exploited for intramolecular relay of chirality. [3] As our model chiral cyclic N-chloramine system we selected N-chloropiperidine azasugars. Polyhydroxylated nitrogen heterocycles such as deoxynojirimycin (DNJ, 1 in Scheme 1) may be considered to be mimics of sugars, for example, d-glucose, in which the ring oxygen has been replaced by a nitrogen atom. [4] The often potent inhibitory activity of many of these compounds towards carbohydrateprocessing enzymes has suggested their use in a wide range of potential therapeutic strategies, [5-8] including the treatment of viral infections [9, 10] and lysosomal storage diseases, [11, 12] and as invaluable tools in the study of enzyme mechanism. [13]
A Concise Enantioselective Entry to the Synthesis of Deoxy-azasugars
Organic Letters - ORG LETT, 2000
A concise enantioselective preparation of oxazolidinylpiperidine 4, a key intermediate in the synthesis of glycosidase inhibitors such as 1-deoxymannojirimycin or 1-deoxygalactostatin, has been developed. Sharpless catalytic asymmetric epoxidation of (E)-2,4-pentadienol followed by treatment with allyl isocyanate afforded epoxy carbamate 8. Regioselective intramolecular ring opening promoted by sodium bis(trimethylsilyl)amide and ring-closing metathesis provided the bicyclic intermediate 4 in high enantiomeric purity. The four-step sequence takes place in 51% overall yield.
Syntheses of New Amino and Aziridino Sugar Derivatives of Potential Biochemical Interest
European Journal of Organic Chemistry, 1987
Efficient one-pot syntheses of some amino and aziridino sugars of potential biochemical interest are developed by way of a CN coupling reaction between suitably protected sugars and esters of p-aminobenzoic acid. The free amino function of the latter are utilized to cause SN2 displacement of the triflyl group in the sugar triflates 1–3 providing a new class of amino sugars (4–8). The reactions of 4 and 5 with Et2OBF3 in trimethylsilyl azide afford a new type of aziridino sugars (9–10) through a novel isomerization of an α-iminooxirane into an α-hydroxyepimine. The reaction pathway also provides benzyl 4-[4-(tert-butyloxycarbonyl)phenylamino]-4-deoxy-β-L-lyxopyranoside (11) and its α-D-isomer 12. The conformation of compounds 4–11 are supported by 1H- and 13C-NMR spectroscopy.Synthesen neuer Amino- und Aziridino-Zuckerderivate von potentieller biochemischer RelevanzEffiziente Eintopfsynthesen für einige Amino- und Aziridinozucker mit potentieller biochemischer Relevanz werden beschrieben. Die Verbindungen werden durch eine CN-Kupplungsreaktion von geschützten Zuckern und Estern der p-Aminobenzoesäure erhalten. Die freie Aminofunktion der letzteren wird durch eine SN2-Reaktion mit der Triflatgruppe der Zuckertriflate 1–3 zu einer neuen Klasse von Aminozuckerderivaten (4–8) umgesetzt. Die Reaktion von 4 und 5 mit Et2OBF3 in Trimethylsilylazid liefert eine neue Klasse von Aziridinozuckern (9–10), welche durch eine Isomerisierung des α-Iminooxirans in ein α-Hydroxyepimin entsteht. Bei dieser Reaktion entstehen außerdem Benzyl-4-[4-(tert-butyloxycarbonyl)phenylamino]-4-deoxy-β-L-lyxopyranosid (11) und dessen α-D-Isomeres 12. Die Konformation der Verbindungen 4–11 wird durch 1H- und 13C-NMR-Spektroskopie bewiesen.