- Anin vitro-in vivosequential cascade for the synthesis of iminosugars from aldoses
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Here, we report a chemoenzymatic approach for the preparation of a small panel of biologically important iminosugars from readily available aldoses. Our approach involves anin vitrotransaminase-mediated amination of aldoses in combination with anin vivose
- Kuska, Justyna,O'Reilly, Elaine,Ryan, James,Taday, Freya,Yeow, Kathryn
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p. 4327 - 4331
(2021/07/12)
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- D-Glucose based syntheses of β-hydroxy derivatives of l-glutamic acid, l-glutamine, l-proline and a dihydroxy pyrrolidine alkaloid
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The β-hydroxy derivatives of l-glutamic acid, l-glutamine and l-proline, useful for peptide/protein studies, were synthesized starting from d-glucose. The C2 carbon in d-glucose provided the carboxylic acid functionality, while the amino and β-hydroxy groups of the amino acids were amenable from the C3 and C4 hydroxy groups of the sugar, respectively. The key intermediate with appropriate carbon framework of the target molecules was constructed by homologation of a suitable azido-d-glucofuranose derivative using the Arndt-Eistert reaction. This journal is
- Kumar, K. S. Ajish,Chattopadhyay, Subrata
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p. 19455 - 19464
(2015/06/09)
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- Highly regioselective oxirane ring-opening of a versatile epoxypyrrolidine precursor of new imino-sugar-based sphingolipid mimics
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An in-depth study of the oxirane ring-opening reaction of a pivotal epoxypyrrolidine is reported. The introduction of various carbon- and heteroatom-centered nucleophiles at C4 has been achieved with high regiocontrol. The structures of the major products were assigned on the basis on an X-ray crystallographic study of six examples. A mechanistic study carried out at the B3LYP/6-31G** level of theory suggested that the steric control of the vinyl substituent was responsible for the regioselectivity. Finally, this approach was used to design and prepare imino-sugar-based sphingolipid mimics. A highly cytotoxic C-octylpyrrolidine is described. This compound was shown to interfere with the metabolism of sphing-olipids in murine melanoma cells, notably in inhibiting the production of glucosylceramide. Wiley-VCH Verlag GmbH & Co. KGaA.
- Rives, Arnaud,Genisson, Yves,Faugeroux, Vanessa,Zedde, Chantal,Lepetit, Christine,Chauvin, Remi,Saffon, Nathalie,Andrieu-Abadie, Nathalie,Colie, Sandra,Levade, Thierry,Baltas, Michel
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experimental part
p. 2474 - 2489
(2009/09/29)
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- Activation of N-Sulfonyl oxaziridines using copper(II) catalysts: Aminohydroxylations of styrenes and 1,3-dienes
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N-Sulfonyl oxaziridines are susceptible to electrophilic activation using copper(II) catalysts and react with styrenes under these conditions to provide 1,3-oxazolidines in a formal aminohydroxylation of the alkene. We propose a two-step mechanism involving a cationic intermediate to account for the rate differences and regioselectivities observed using a variety of styrenes. In accord with our hypothesis, aminohydroxylations of a range of substrates bearing electron-stabilizing groups are successful, and 1,3-dienes are particularly good substrates for copper(II)-catalyzed aminohydroxylation. Reactions of unsymmetrical dienes provide good to excellent olefin selectivity, the sense and magnitude of which can be rationalized upon consideration of the stability of the cationic intermediates suggested by our mechanism. Diastereoselective synthesis of a diverse range of densely functionalized structures can be achieved by polyfunctionalization of dienes using aminohydroxylation as a key complexity-increasing step.
- Michaelis, David J.,Ischay, Michael A.,Yoon, Tehshik P.
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p. 6610 - 6615
(2008/12/22)
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- C-Alkyl 5-membered ring imino sugars as new potent cytotoxic glucosylceramide synthase inhibitors
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The stereoselective preparation of C-alkyl 5-membered ring imino sugars, their biological evaluation with regard to glucosyleramide synthase (GCS) inhibition, and cytotoxicity in a murine melanoma B16 cell model, were investigated. It was found that epoxy
- Faugeroux, Vanessa,Genisson, Yves,Andrieu-Abadie, Nathalie,Colie, Sandra,Levade, Thierry,Baltas, Michel
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p. 4437 - 4439
(2008/09/18)
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- The stereochemical course of addition of allyltrimethylsilane to protected L-alaninals and L-serinals in the presence of Lewis acids. Total synthesis of cis-(2R,3S)-3-hydroxyproline
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The influence of Lewis acids on the diastereoselectivity of the addition of allyltrimethylsilane to variously protected L-alaninals and L-serinals was investigated and high levels of asymmetric induction were achieved. Stereochemical models for rationalisation of the results obtained are proposed. cis-(2R,3S)-3-Hydroxyproline was synthesised starting from N-Cbz, O-TBS-L-serinal, in which the crucial step involves addition of allyltrimethylsilane to the aldehyde in the presence of SnCl4.
- Gryko,Prokopowicz,Jurczak
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p. 1103 - 1113
(2007/10/03)
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- Efficient synthesis of 3-hydroxyprolines and 3-hydroxyprolinols from sugars
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trans-3-Hydroxy-L-proline 1, trans-3-hydroxy-L-prolinol 2, cis-3-hydroxy-D-proline 3, and cis-3-hydroxy-D-prolinol 4 have been prepared in enantiomerically pure form with chirospecific manner. Key intermediates, 2-amino-3-hydroxy-4-pentenoate 9 and 17, were obtained from D-glucono-δ-lactone and L-gulonic acid γ-lactone via a simultaneous dealkoxyhalogenation.
- Lee, Jin Hwan,Kang, Jae Eun,Yang, Min Suk,Kang, Kyu Young,Park, Ki Hun
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p. 10071 - 10076
(2007/10/03)
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- Oligonucleotides with 3-hydroxy-N-acetylprolinol as sugar substitute
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Fully modified oligonucleotides were synthesised from the 3-O-phosphoramidites of monomethoxytritylated trans-3-hydroxy-N-[(N6-benzoyladenin-9-yl)-acetyl]-prolinol [(2S,3R) and (2R,3S) series], trans-3-hydroxy-N-[(thymin-1-yl)-acetyl]-prolinol [(2S,3R) and (2R,3S) series], and cis-3-hydroxy-N-[(N6-benzoyl-adenin-9-yl)-acetyl]-L-prolinol (2R,3R). Remarkably, as well the L-trans (2R,3S) as the D-trans (2S,3R) all-adenine oligonucleotides are capable of hybridisation with complementary DNA and RNA. With modified all-thymine trans-oligomers no complexation with natural nucleic acids was observed. However, complex formation between two modified strands of the same sense of chirality does occur with formation of a triple stranded complex. The all-thymine oligonucleotides with trans-3-HO-N-acetylprolinol backbone are capable of hybridisation with trans-4-HO-N-acetylprolinol oligoadenylates of the same enantiomeric form in both the D and the L series, and inversely, the all-adenine oligonucleotide with the trans-3-HO conformation hybridises with the trans-4-HO oligothymidylates. While the former interactions have a triple stranded origin, the latter are 1:1 interactions. No interactions were noticed upon mixing oligonucleotide analogues of different sense of chirality. Modified mixed trans-3-HO A,T sequences display no hybridisation with complementary nucleic acids, nor homocomplex formation. The L-cis all-adenine oligonucleotide hybridises with its RNA complement. Several complexes were investigated by circular dichroism and microcalorimetry. In conclusion, the 3-hydroxy-N-acetylprolinol system represents an example of homochiral oligonucleotides built up from two enantiomeric forms and hybridizing both with natural nucleic acids.
- Ceulemans, Griet,Van Aerschot, Arthur,Rozenski, Jef,Herdewijn, Piet
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p. 14957 - 14974
(2007/10/03)
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- A flexible synthesis of azasugars and homoazasugars via olefin metathesis
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A flexible synthesis of azasugars and homoazasugars from vinyl glycine methyl ester is described. The syntheses, which are based on ring closing olefin metathesis steps and stereocontrolled functionalizations of the formed double bonds, offer a broad vari
- Huwe, Christoph M.,Blechert, Siegfried
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- A novel approach to azasugars from vinyl glycine methyl ester via olefin metathesis
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A novel strategy for the synthesis of azasugars from vinyl glycine methyl ester was designed, using an olefin metathesis as a key step. As a first test of this strategy, rac-trans-2-hydroxymethyl-3-hydroxypyrrolidine, which was isolated as the (2R,3S)-iso
- Huwe, Christoph M.,Blechert, Siegfried
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p. 1621 - 1624
(2007/10/02)
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- A concise diastereoselective synthesis of the natural (2R, 3S)2-hydroxymethyl-3-hydroxy pyrrolidine
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(2R, 3S)-2-hydroxymethyl-3-hydroxy pyrrolidine 4, a constituent of CAstanospermum ausfrale, 1 was synthesized from (S)-pyroglutamic acid through diastereoselective epoxidation of α, β-unsaturated pyrrolidone 8.
- Griffart-Brunet, Dominique,Langlois, Nicole
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p. 119 - 122
(2007/10/02)
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- Electrophilic Olefin Heterocyclization in Organic Synthesis. Stereoselective Synthesis of 4,5-Disubstituted γ-Lactams by Iodine-Induced Lactam Formation of γ,δ-Unsaturated Thioimidates
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Iodine-induced lactamization of γ,δ-unsaturated thioimidates proceeds regioselectively to provide γ-lactams.The iodolactamization with allylic substituents brings about 1,2-asymmetric induction, which depends on the allyl groups.Transformation of the cis-4-hydroxy-5-(iodomethyl)pyrrolidin-2-one (24a) among these highly functionalized γ-lactams into several biologically active compounds is described.In addition, the conversion of an optically active form of 24a is discussed.
- Takahata, Hiroki,Takamatsu, Tamotsu,Yamazaki, Takao
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p. 4812 - 4822
(2007/10/02)
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