Oxime-based methods for synthesis of stereodefined acyclic polyfunctionalized δ-azido-nitriles and 5-substituted isoxazoles from carbohydrate derivatives

Passacantilli, Pietro; Pepe, Simona; Piancatelli, Giovanni; Pigini, Daniela; Squarcia, Antonella

doi:10.1016/j.tet.2004.06.050

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…Since the mechanism of the Beckmann fragmentation requires reagents with dehydrating properties, [5,6,11] the ketoximes 3a,b were treated with mesyl chloride and triethylamine in dichloromethane at room temp., a reagent combination previously utilized for this purpose. [24] Scheme 1. Reagents and conditions: a) PDC, CH 3 Surprisingly, we observed a very fast reaction (15 min) leading directly to the regioselective formation of (E,2R,3R)-2,3-bis(benzyloxy)-5-methoxypent-4-enenitrile (4a) and (E,2S,3R)-2,3-bis(benzyloxy)-5-methoxypent-4-enenitrile (4b) as the only reaction products and in acceptable yields (60Ϫ70%).…”

Section: Resultsmentioning

confidence: 99%

“…All the starting materials were prepared in one step from O-benzyl derivatives of glycals and glycosyl glycals according to our previously reported procedure by reaction with Tl(NO 3 ) 3 /NaBH 4 reagent combination in methanol. [15,16,24] The C2 free hydroxy groups of 1a,b (available from Obenzyl derivatives of -glucal and -galactal, respectively) were easily oxidized to the corresponding ketones 2a,b in high yield (90Ϫ95%) by reaction with PDC in acetonitrile (Scheme 1). The reaction of compounds 2a,b with three equivalents of hydroxylamine, prepared from hydroxylamine hydrochloride and triethylamine in a 1:1 EtOH/THF solution, gave ketoximes 3a,b as E/Z stereoisomeric mixtures (75Ϫ80%).…”

Section: Resultsmentioning

confidence: 99%

“…[15,16,24] Since compounds 5a,b and 10b,e have not been described before, we report the analytical data in the Expt. Sect..…”

Section: Generalmentioning

confidence: 99%

“…Compound 5b was prepared from perbenzylated -arabinal (200 mg, 0.67 mmol) by following our previously described method, [15,16] and was obtained as a viscous oil (122 mg, 55% Linear Methoxy Alcohol 10e: Compound 10e was prepared from perbenzylated gentiobial [24] (200 mg, 0.23 mmol) by following our previously described method, [15,16] and was obtained as a viscous oil (124 mg, 60% Preparation of Aldehydes 18a,b. General Procedure: 4  HCl (1 mL) was added to a solution of the appropriate enol ether (0.60 mmol) in THF (5 mL) and then stirred at room temperature for 4 h. The reaction mixture was diluted with Et 2 O and washed in a separating funnel with NaHCO 3 , H 2 O, brine and dried with anhydrous Na 2 SO 4 .…”

Section: Linear Methoxy Alcohol 5bmentioning

confidence: 99%

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Neighboring‐Group Participation in Nitrile‐Forming Beckmann Fragmentation Reactions: Synthesis of Enantiopure (E)‐2,3‐Di‐O‐substituted‐5‐methoxy‐ pent‐4‐enenitriles and Their Conversion into Pyranosylamines

et al. 2004

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The selective Beckmann fragmentations of multifunctionalised ketoximes have been proven to proceed effectively to give the corresponding nitriles. The chiral (E)-1,3,4-tri-Osubstituted-6-methoxy-hex-5-en-2-one oxime derivatives, available from glycals and glycosyl glycals, gave enantiopure (E)-2,3-di-O-substituted-5-methoxypent-4-enenitriles by treatment with mesyl chloride and triethylamine. The C1−C2 heterolytic fragmentation was completely controlled and directed by the adjacent C1 ether oxygen, which generates a

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…[15,16,24] Since compounds 5a,b and 10b,e have not been described before, we report the analytical data in the Expt. Sect..…”

Section: Generalmentioning

confidence: 99%

Section: Linear Methoxy Alcohol 5bmentioning

confidence: 99%

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Neighboring‐Group Participation in Nitrile‐Forming Beckmann Fragmentation Reactions: Synthesis of Enantiopure (E)‐2,3‐Di‐O‐substituted‐5‐methoxy‐ pent‐4‐enenitriles and Their Conversion into Pyranosylamines

et al. 2004

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“…Condensation between aldehyde 14 and hydroxylamine, 30) followed by hydrogenation 31) and protection of the amine produced compound 15, at 78% yield. The following transformation to the target compound 3b was achieved by the same procedure as the synthesis of compound 3a.…”

Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Non-peptide RGD Mimics for Evaluation of Their Utility as Anti-platelet Agents

Higuchi

Hikita

Murayama

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and WielandMiescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC 50 values of 3e were 0.91 mM (ADP initiation) and 0.54 mM (collagen initiation).Key words non-peptide Arg-Gly-Asp (RGD) mimic; antiplatelet agent; dehydroepiandrosterone; WielandMiescher ketone; Hajos-Parrish ketone Platelets play an important role in hemostasis; however, its aggregation triggers several serious diseases, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Platelet aggregation process is occurred by the stimulation of various physiological activators such as ADP, collagen and thrombin.1,2) Finally the stimulation derives the structural transformation of glycoprotein IIb/IIIa (integrin αIIbβ3) on the platelet surface. The activated GPIIb/IIIa receptor interacts with fibrinogen to induce platelet aggregation. [3][4][5] The interaction between GPIIb/IIIa and fibrinogen is mediated by the Arg-Gly-Asp (RGD) sequence in fibrinogen.6-8) Additionally, the β-turn structure formed by the sequence enhances the interaction of each molecules.9,10) Therefore, RGD mimics are valuable platelet aggregation antagonists, and many compounds have been developed. [11][12][13][14] Among them, tirofiban (1) 15) and eptifibatide (2), 16) were launched for clinical use (Fig. 1). To develop a more efficient approach to RGD mimics, we assumed that the shape and volume of the β-turn structure is equal to that of perhydro polycyclic hydrocarbon structures such as perhydro-phenanthrene, 17,18) -naphthalene, and -indene (Fig. 2). Therefore, these hydrocarbons, with acidic and basic moieties of the appropriate position and size, were hypothesized to be good candidate for antiplatelet agents. Moreover, such compounds should be biologically stable and show better oral bioavailability than the peptide ligands. Additionally, a method for stereoselective transformation of such compounds is available, based on established concepts in steroid chemistry, enabling detailed conformational analysis of the ligand docking site. We planned to develop a method for synthesis of the orally active antiplatelet agents 3a-e from the readily available dehydroepiandrosterone (4) and Wieland-Miescher (5) and Hajos-Parrish ketones (6). Herein, we report the synthesis of the target peptide mimic compounds and an evaluation of those antiplatelet activities. ChemistryFirst, for preparation of the perhydrophenanthrene compounds 3a and b, the common intermediate 11 was synthesized from dehydroepiandrosterone 4 (Chart 1). Acetalization of the ketone 4 19) and Oppenauer oxidation of the secondary alcohol accompanying isomerization of the olefin yielded an enone.20) The stereoselecti...

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