[1,4]-sigmatropic rearrangement of chiral nitrones and their utilization in the synthesis of new iminosugars.

Reflection on the epimerization of the α-stereocenter of sugar nitrones leads to the conclusion that the process may occur through [1,4]-sigmatropic rearrangement. Participation of an ionic mechanism was excluded by a deuterium labeling experiment, and DFT calculations showed a reasonable energy barrier for the proposed [1,4]-shift. Products of the intramolecular 1,3-dipolar cycloaddition of the studied nitrones were utilized in the diversity-oriented synthesis of polyhydroxy derivatives of piperidine, indolizidine and quinolizidine. Minimal activity against the screened glucosidases and human melanoma cell lines was observed for some of the obtained compounds.

[1]  Izabela D. Madura,et al.  Epimerization of the α Stereocenter in d‐Ribose‐Derived Nitrones: Direct Access to Variant Quinolizidines with d‐Ribo and d‐Arabino Configurations , 2015 .

[2]  S. Py,et al.  Hydroxymethyl-Branched Polyhydroxylated Indolizidines: Novel Selective α-Glucosidase Inhibitors. , 2015, Organic letters.

[3]  P. Merino,et al.  Mechanism Switch in Mannich‐Type Reactions: ELF and NCI Topological Analyses of the Reaction between Nitrones and Lithium Enolates , 2015 .

[4]  S. Sabharwal,et al.  Synthesis, conformational study, glycosidase inhibitory activity and molecular docking studies of dihydroxylated 4- and 5-amino-iminosugars. , 2015, Carbohydrate research.

[5]  R. Ziessel,et al.  Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores , 2015, Beilstein journal of organic chemistry.

[6]  M. Bergeron-Brlek,et al.  Direct synthesis of imino-C-nucleoside analogues and other biologically active iminosugars , 2015, Nature Communications.

[7]  Shibin Chacko,et al.  Diastereoselective Synthesis of 1-Deoxygalactonojirimycin, 1-Deoxyaltronojirimycin, and N-Boc-(2S,3S)-3-Hydroxypipecolic Acid via Proline Catalyzed α-Aminoxylation of Aldehydes. , 2015, The Journal of organic chemistry.

[8]  M. Wormald,et al.  3-Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar. , 2015, The Journal of organic chemistry.

[9]  S. Hirono,et al.  Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal α-Glucosidases: Binding Conformation and Interaction for ntSI. , 2015, The Journal of organic chemistry.

[10]  Qin Li,et al.  Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds , 2015 .

[11]  P. Merino,et al.  Understanding bond formation in polar one-step reactions. Topological analyses of the reaction between nitrones and lithium ynolates. , 2015, The Journal of organic chemistry.

[12]  E. Maziarz,et al.  Synthesis of polyhydroxylated piperidine and pyrrolidine peptidomimetics via one-pot sequential lactam reduction/Joullié-Ugi reaction. , 2015, The Journal of organic chemistry.

[13]  Izabela D. Madura,et al.  Unprotected Xylose‐Derived Nitrone in Stereodivergent Synthesis of 4‐Hydroxypiperidine Enantiomers: Weak Lewis Acid Induced Alteration of Stereochemistry in 1,3‐Dipolar Cycloaddition , 2015 .

[14]  S. Mekelleche,et al.  Regio- and diastereoselectivity of the 1,3-dipolar cycloaddition of α-aryl nitrone with methacrolein. A theoretical investigation , 2015 .

[15]  S. Castanys,et al.  Antileishmanial activity of sp2-iminosugar derivatives , 2015 .

[16]  P. Compain,et al.  Iminosugars as a new class of cholinesterase inhibitors. , 2015, Bioorganic & medicinal chemistry letters.

[17]  Elena Lenci,et al.  Skeletal diversity from carbohydrates: use of mannose for the diversity-oriented synthesis of polyhydroxylated compounds. , 2015, The Journal of organic chemistry.

[18]  S. Sabharwal,et al.  Halogenated D-xylono-δ-lactams: synthesis and enzyme inhibition study. , 2015, Carbohydrate research.

[19]  S. Jarosz,et al.  Ruthenium-catalyzed one-pot ring-closing metathesis/syn-dihydroxylation in the synthesis of bicyclic iminosugars , 2015 .

[20]  R. Jasiński.  A stepwise, zwitterionic mechanism for the 1,3-dipolar cycloaddition between (Z)-C-4-methoxyphenyl-N-phenylnitrone and gem-chloronitroethene catalysed by 1-butyl-3-methylimidazolium ionic liquid cations , 2015 .

[21]  J. Behr,et al.  Glycosidase inhibitors from the roots of Glyphaea brevis. , 2015, Phytochemistry.

[22]  L. Hunter,et al.  A d-ribose-derived α-amino nitrile as a versatile intermediate for the collective synthesis of piperidine-type iminosugar C-glycosides , 2014 .

[23]  E. Álvarez,et al.  Synthesis of multibranched australine derivatives from reducing castanospermine analogues through the Amadori rearrangement of gem-diamine intermediates: selective inhibitors of β-glucosidase. , 2014, The Journal of organic chemistry.

[24]  C. Matassini,et al.  Polyhydroxyamino‐Piperidine‐Type Iminosugars and Pipecolic Acid Analogues from a D‐Mannose‐Derived Aldehyde , 2014 .

[25]  P. Merino,et al.  DFT investigation of the mechanism of E/Z isomerization of nitrones. , 2014, The Journal of organic chemistry.

[26]  Xin Yang,et al.  Mechanism and regioselectivity of the cycloaddition between nitrone and dirhodium vinylcarbene catalyzed by Rh2(O2CH)4: a computational study , 2014, Theoretical Chemistry Accounts.

[27]  Y. D. Vankar,et al.  Synthesis and Glycosidase Inhibition Study of 2‐C‐Hydroxymethyl‐ and 6‐C‐Hydroxymethyl‐Branched Piperidines from D‐Glucose Using Ene‐Yne Metathesis as a Key Step , 2014 .

[28]  M. Chmielewski,et al.  Five- and Six-membered Cyclic Nitrones Derived from Sugars and Hydroxyacids: Synthesis and Applications , 2014 .

[29]  H. Eshghi,et al.  Density functional theory study of the regio and stereoselectivity in 1,3-dipolar cycloddition reactions between N-methyl methylenenitrone and fluorinated dipolarophiles , 2014 .

[30]  Yifa Zhou,et al.  Cell cycle arrest, apoptosis and autophagy induced by iminosugars on K562 cells. , 2014, European journal of pharmacology.

[31]  T. Opatz,et al.  Ring expansion of 1,2,3,4-tetrahydroisoquinolines to dibenzo[c,f]azonines. An unexpected [1,4]-sigmatropic rearrangement of nitrile-stabilized ammonium ylides. , 2014, The Journal of organic chemistry.

[32]  A. Brandi,et al.  Recent syntheses and biological activity of lentiginosine and its analogues. , 2014, Current topics in medicinal chemistry.

[33]  B. Ayers,et al.  One-Pot Tandem Strecker Reaction and Iminocyclisations: Syntheses of Trihydroxypiperidine α-Iminonitriles , 2014 .

[34]  A. Fortes,et al.  Synthesis of Iminosugars from Tetroses , 2014 .

[35]  Y. D. Vankar,et al.  Synthesis of pyrrolidine iminosugars, (−)-lentiginosine, (−)-swainsonine and their 8a-epimers from D-glycals , 2014 .

[36]  P. S. Kumar,et al.  A diversity oriented one-pot synthesis of novel iminosugar C-glycosides. , 2014, Chemical communications.

[37]  H. Reissig,et al.  Synthesis of a Series of Enantiopure Polyhydroxylated Bicyclic N‐Heterocycles from an L‐Erythrose‐Derived Nitrone and Alkoxyallenes , 2014 .

[38]  Mariola Koszytkowska-Stawińska,et al.  Convenient synthesis of epimeric indolizidines by the intramolecular 1,3-dipolar cycloaddition of a sugar derived N-(3-alkenyl)nitrone , 2013 .

[39]  S. Jarosz,et al.  Synthesis of polyhydroxylated quinolizidines and azaspiro[4.5]decanes from D-xylose. , 2013, Organic letters.

[40]  P. Merino,et al.  Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones , 2013 .

[41]  H. Reissig,et al.  Stereocomplementary routes to hydroxylated nitrogen heterocycles: total syntheses of casuarine, australine, and 7-epi-australine. , 2013, Chemistry.

[42]  J. Joglar,et al.  Chemo-enzymatic synthesis and glycosidase inhibitory properties of DAB and LAB derivatives. , 2013, Organic & biomolecular chemistry.

[43]  A. Lumbroso,et al.  Stereodivergent synthesis of iminosugars from stannylated derivatives of (S)-vinylglycinol. , 2013, Organic letters.

[44]  Jinhong Chang,et al.  Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents , 2013, Emerging Microbes & Infections.

[45]  Y. Kita,et al.  Protecting-group-free catalytic asymmetric total synthesis of (−)-rosmarinecine , 2012 .

[46]  Pranaya V. Joshi,et al.  α-Geminal dihydroxymethyl piperidine and pyrrolidine iminosugars: synthesis, conformational analysis, glycosidase inhibitory activity, and molecular docking studies. , 2012, The Journal of organic chemistry.

[47]  G. Bifulco,et al.  Natural Iminosugar (+)-Lentiginosine Inhibits ATPase and Chaperone Activity of Hsp90 , 2012, PloS one.

[48]  G. Fleet,et al.  Iminosugars as therapeutic agents: recent advances and promising trends. , 2011, Future medicinal chemistry.

[49]  P. Merino,et al.  Sequential nucleophilic addition/intramolecular cycloaddition to chiral nonracemic cyclic nitrones: a highly stereoselective approach to polyhydroxynortropane alkaloids. , 2011, The Journal of organic chemistry.

[50]  D. H. Williams,et al.  Iminosugars past, present and future: medicines for tomorrow. , 2011, Drug discovery today.

[51]  F. Wilson,et al.  Therapeutic applications of iminosugars: current perspectives and future opportunities. , 2011, Progress in medicinal chemistry.

[52]  A. Michalik,et al.  Steviamine, a new indolizidine alkaloid from Stevia Rebaudiana , 2010 .

[53]  G. Fleet,et al.  Synthesis and glycosidase inhibition of the enantiomer of (-)-steviamine, the first example of a new class of indolizidine alkaloid. , 2010, Organic letters.

[54]  J. T. Vázquez,et al.  Intramolecular 1,3-dipolar cycloaddition of N-alkenyl nitrones en route to glycosyl piperidines , 2009 .

[55]  R. Plantier-Royon,et al.  The spirocyclopropyl moiety as a methyl surrogate in the structure of l-fucosidase and l-rhamnosidase inhibitors. , 2009, Bioorganic & medicinal chemistry.

[56]  A. T. Soldatenkov,et al.  Rearrangement of the cyanomethyl group in cycloammonium zwitterions generated from spiro-4-cyanomethyl-3-methyl-1,2,3,4,5,6-hexahydrobenzo[f]isoquinolinium-1,2'-(1',2',3',4'-tetrahydronaphthalen-1'-one) chloride , 2009 .

[57]  D. Watkin,et al.  Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR)-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol hydrobromide] , 2009, Acta crystallographica. Section E, Structure reports online.

[58]  V. Ranade.  Iminosugars-From Synthesis to Therapeutic Applications , 2009 .

[59]  Joëlle Pérard-Viret,et al.  Synthesis and evaluation of substituted indolizidines as peptidomimetics of RGD tripeptide sequence , 2009 .

[60]  N. Shankaraiah,et al.  Studies towards the construction of quaternary indolizidines by [2,3]-sigmatropic rearrangement cocatalyzed by ionic liquid , 2009 .

[61]  R. Weis,et al.  Antimycobacterial and H1-antihistaminic activity of 2-substituted piperidine derivatives. , 2008, Bioorganic & medicinal chemistry.

[62]  Yi Deng,et al.  Synthesis, characterization and antibacterial properties of multifunctional hindered amine light stabilizers , 2008 .

[63]  R. Weis,et al.  Antimycobacterial activity of diphenylpyraline derivatives. , 2008, European journal of medicinal chemistry.

[64]  T. Wrodnigg,et al.  Natural and synthetic iminosugars as carbohydrate processing enzyme inhibitors for cancer therapy. , 2008, Anti-cancer agents in medicinal chemistry.

[65]  V. Nair,et al.  Intramolecular 1,3-dipolar cycloaddition reactions in targeted syntheses , 2007 .

[66]  P. Merino,et al.  Experimental and theoretical evidences of 2-aza-Cope rearrangement of nitrones , 2007 .

[67]  H. Pellissier.  Asymmetric 1,3-Dipolar Cycloadditions , 2007 .

[68]  C. Tarnus,et al.  Creation of quaternary stereocentres: synthesis of new polyhydroxylated indolizidines , 2006 .

[69]  J. Neuss,et al.  A novel Diels-Alder approach to heavily substituted azasugars , 2003 .

[70]  U. Kazmaier,et al.  Synthesis of Monocyclic and Bicyclic Imino Sugars , 2003 .

[71]  B. G. Davis,et al.  Nitrogen inversion as a diastereomeric relay in azasugar synthesis: the first synthesis of adenophorine. , 2003, Angewandte Chemie.

[72]  K. Gothelf,et al.  Nucleophilic addition of nitrones to ketones: development of a new catalytic asymmetric nitrone-aldol reaction. , 2002, Chemistry.

[73]  Hideyuki Sato,et al.  Total Synthesis of (+)-Myriocin and (−)-Sphingofungin E from Aldohexoses Using Overman Rearrangement as the Key Reaction , 2002 .

[74]  A. Brandi,et al.  Stereodivergent Approach to Enantiopure Hydroxyindolizidines Through 1,3‐Dipolar Cycloaddition of 3‐Hydroxypyrroline N‐Oxide Derivatives , 2002 .

[75]  B. G. Davis,et al.  Novel cyclic sugar imines: carbohydrate mimics and easily elaborated scaffolds for aza-sugars. , 2002, Organic letters.

[76]  V. Langer,et al.  Synthesis and structure determination of some sugar amino acids related to alanine and 6-deoxymannojirimycin. , 2001, Carbohydrate research.

[77]  M. Cacciarini,et al.  Total synthesis of (-)-rosmarinecine by intramolecular cycloaddition of (S)-malic acid derived pyrroline N-oxide. , 2001, Organic letters.

[78]  Anna Budzińska,et al.  Asymmetric synthesis of a branched-chain analogue of azapyranoses from a 5-allylic derivative of 5-nitro-1,3-dioxane. Synthesis of (3 R ,4 S )-6,6-bis(hydroxymethyl)-3,4-dihydroxypiperidin-2-one , 2001 .

[79]  W. Sas,et al.  Asymmetric synthesis of novel polyhydroxylated derivatives of indolizidine and quinolizidine by intramolecular 1,3-dipolar cycloaddition of N-(3-alkenyl)nitrones , 2001 .

[80]  A. Brandi,et al.  Stereoselective approach to hydroxyindolizidines: protection/deprotection of the nitrone functionality via cycloaddition/retrocycloaddition. , 2000, Organic letters.

[81]  M. Scheer,et al.  On the pathway of the η1–η5 migration of a Cp* ligand , 2000 .

[82]  A. Stütz.  Iminosugars as glycosidase inibitors [i.e. inhibitors] : Nojirimycin and beyond , 1999 .

[83]  K. Thompson,et al.  PHOTOCHEMICAL ADDITION OF 2,2,2-TRIFLUOROETHANOL TO BENZONITRILE AND P-, M-, AND O-METHYLBENZONITRILE , 1998 .

[84]  A. Jończyk,et al.  [1,4] and [2,3] Sigmatropic rearrangements of ylides generated from N-(α-cyano)allyl-N-cyanomethyl-N,N-dimethylammonium perchlorates , 1996 .

[85]  A. Jończyk,et al.  On the [1,4] sigmatropic rearrangement of ammonium benzylides , 1995 .

[86]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[87]  A. Jończyk,et al.  Reaction of organic anions. 166. Sigmatropic rearrangements of ammonium benzylides: new preparative and mechanistic aspects , 1991 .

[88]  M. Majchrzak,et al.  Thermolysis of 2-acyloxy-Δ3-1,3,4-oxadiazolines. Evidence for a preferred sense of cycloreversion to carbonyl ylides and for fast 1,4-sigmatropic ylide rearrangement , 1989 .

[89]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[90]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[91]  H. Piotrowska,et al.  Palladium catalyzed C-allylation of nitroalkanes , 1982 .

[92]  T. Laird,et al.  Base catalysed rearrangements involving ylide intermediates. Part 1. The rearrangements of diallyl- and allylpropynyl-ammonium cations , 1980 .

[93]  Andrea Vasella.  Stereoselektivität und Reaktivität bei der 1,3‐dipolaren Cycloaddition chiraler N‐(Alkoxyalkyl)nitrone , 1977 .

[94]  J. Tronchet,et al.  Dérivés C‐glycosyliques. VII. Synthèse et réactions de nitrones dérivées de sucres. Communication préliminaire , 1972 .

[95]  L. B. Volodarskii,et al.  Production of stable nitroxide radicals of 3-imidazoline-3-oxide , 1971 .