- Asymmetric total syntheses of (+)-2,5-dideoxy-2,5-imino-D-glucitol [(+)-DGDP] and (?)-1-deoxymannojirimycin [(?)-DMJ] via an extended chiral 1,3-oxazine
-
The asymmetric total syntheses of (+)-2,5-dideoxy-2,5-imino-D-glucitol [(+)-DGDP] 1 and (?)-1-deoxymannojirimycin [(?)-DMJ] 2 were achieved using an extended chiral 1,3-oxazine. The key synthetic strategies included extension of the chirality of anti,syn-oxazine 3 using diastereoselective dihydroxylation, and piperidine and pyrrolidine ring formation. Starting from readily available anti,syn-oxazine 3, (+)-DGDP 1 was synthesized in 5 steps with 31.6% overall yield and (?)-DMJ 2 was synthesized in 4 steps with 60.6% overall yield.
- Myeong, In-Soo,Jung, Changyoung,Kim, Ji-Yeon,Park, Seok-Hwi,Ham, Won-Hun
-
p. 2422 - 2425
(2018/05/25)
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- Conformational Behaviour of Azasugars Based on Mannuronic Acid
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A set of mannuronic-acid-based iminosugars, consisting of the C-5-carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH-dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an “inverted” 1C4 chair conformation as opposed to the “normal” 4C1 chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Because of this solution-phase behaviour, the mannuronic acid ester azasugar was examined as an inhibitor for a Caulobacter GH47 mannosidase that hydrolyses its substrates by way of a reaction itinerary that proceeds through a 3H4 transition state. No binding was observed for the mannuronic acid ester azasugar, but sub-atomic resolution data were obtained for the DMJ?CkGH47 complex, showing two conformations—3S1 and 1C4—for the DMJ inhibitor.
- van Rijssel, Erwin R.,Janssen, Antonius P. A.,Males, Alexandra,Davies, Gideon J.,van der Marel, Gijsbert A.,Overkleeft, Herman S.,Codée, Jeroen D. C.
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p. 1297 - 1304
(2017/07/07)
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- Transforming flask reaction into cell-based synthesis: Production of polyhydroxylated molecules via engineered Escherichia coli
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Dihydroxyacetone phosphate (DHAP)-dependent aldolases have been intensively studied and widely used in the synthesis of carbohydrates and complex polyhydroxylated molecules. However, strict specificity toward donor substrate DHAP greatly hampers their synthetic utility. Here, we transformed DHAP-dependent aldolases-mediated by in vitro reactions into bioengineered Escherichia coli (E. coli). Such flask-to-cell transformation addressed several key issues plaguing in vitro enzymatic synthesis: (1) it solves the problem of DHAP availability by in vivo-hijacking DHAP from the glycolysis pathway of the bacterial system, (2) it circumvents purification of recombinant aldolases and phosphatase, and (3) it dephosphorylates the resultant aldol adducts in vivo, thus eliminating the additional step for phosphate removal and achieving in vivo phosphate recycling. The engineered E. coli strains tolerate a wide variety of aldehydes as acceptor and provide a set of biologically relevant polyhydroxylated molecules in gram scale.
- Wei, Mohui,Li, Zijie,Li, Tiehai,Wu, Baolin,Liu, Yunpeng,Qu, Jingyao,Li, Xu,Li, Lei,Cai, Li,Wang, Peng George
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p. 4060 - 4065
(2015/11/11)
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- Asymmetric syntheses of (-)-1-deoxymannojirimycin and (+)-1- deoxyallonojirimycin via a ring-expansion approach
-
The asymmetric syntheses of (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin are described herein. The ring-closing iodoamination of two epimeric bishomoallylic amines to give the corresponding 5-iodomethylpyrrolidines was followed by in situ ring-expansion to give two diastereoisomerically pure (>99:1 dr) cyclic carbonates. Subsequent deprotection gave (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin as single diastereoisomers in 7.4 and 3.3% overall yield, respectively, from commercially available starting materials.
- Davies, Stephen G.,Figuccia, Aude L. A.,Fletcher, Ai M.,Roberts, Paul M.,Thomson, James E.
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p. 2042 - 2045
(2013/06/05)
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- Asymmetric synthesis of 1-deoxyazasugars from chiral aziridines
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A general and facile synthesis of enantiopure 1-deoxyazasugars was achieved from stereoselective dihydroxylation of a common synthetic intermediate, piperidine ring fused oxazolidin-2-one, originating from a commercially available starting substrate, chiral aziridine-2-carboxylate, in high yields. The Royal Society of Chemistry 2011.
- Singh, Alok,Kim, Bongchan,Lee, Won Koo,Ha, Hyun-Joon
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experimental part
p. 1372 - 1380
(2011/04/16)
-
- An expeditious synthesis of iminosugars
-
A short and expedient synthesis of the potent glycosidase inhibitors, 1-deoxynojirimycin, miglitol, miglustat, 1-deoxymannojirimycin, and 1-deoxygalactonojirimycin is presented.
- Gandy, Michael N.,Piggott, Matthew J.,Stubbs, Keith A.
-
experimental part
p. 1409 - 1412
(2011/05/14)
-
- Straightforward synthesis of diverse 1-deoxyazapyranosides via stereocontrolled nucleophilic additions to six-membered cyclic nitrones
-
A systematic study of diastereoselective nucleophilic addition of Grignard reagents to six-membered chiral tri-O-benzyl cyclic nitrones is described. With all eight chiral cyclic nitrones and asymmetric reaction conditions in hand, a practical methodology is established for the preparation of diverse 1-deoxyazapyranosides bearing various stereogenic centers. We have developed practical methods to prepare all eight six-membered chiral cyclic nitrones. Using these cyclic nitrones and diastereoselective nucleophilic additions, 12 examples of diverse 1-deoxyazapyranosides including enantiomers were synthesized to demonstrate the generality and flexibility of this new approach.
- Chan, Ting-Hao,Chang, Yi-Fan,Hsu, Jung-Jung,Cheng, Wei-Chieh
-
supporting information; experimental part
p. 5555 - 5559
(2011/01/05)
-
- D-fructose-6-phosphate aldolase in organic synthesis: Cascade chemical-enzymatic preparation of sugar-relafed polyhydroxylated compounds
-
Novel aldol addition reactions of dihydroxyacetone (DHA) and hydroxyacetone (HA) to a variety of aldehydes catalyzed by D-fructose-6-phosphate aldolase (FSA) are presented. In a chemical-enzymatic cascade reaction approach, 1-deoxynojirimycin and 1-deoxymannojirimycin were synthesized starting from (R)- and (S)-3-(N-Cbz-amino)-2-hydroxypropanal, respectively. Furthermore, 1,4-dideoxy1,4-imino-D-arabinitol and 1,4,5-trideoxy-1,4-imino-D-arabinitol were prepared from N-Cbz-glycinal, 1 -Deoxy-D-xylulose was also synthesized by using HA as the donor and either 2-benzyloxyethanal or 2-hydroxyethanal as acceptors. In both cases the enzymatic aldol addition reaction was fully stereoselective, but with 2-hydroxyethanal 17% of the epimeric product at C2, 1-deoxy-D-erythro-2-pentulose, was observed due to enolization/epimerization during the isolation steps. It was also observed that D-(-)-threose is a good acceptor substrate for FSA, opening new synthetic possibilities for the preparation of important novel complex carbohydrate-related compounds from aldoses. To illustrate this, 1-deoxy-D-ido-hept-2-ulose was obtained stereoselectively by the addition of HA to D-(-)-threose, catalyzed by FSA. It was found that the reaction performance depended strongly on the donor substrate, HA being the one that gave the best conversions to the aldol adduct. The examples presented in this work show the valuable synthetic potential of FSA for the construction of chiral complex polyhydroxylated sugar-type structures.
- Concia, Alda Lisa,Lozano, Caries,Castillo, Jose A.,Parella, Teodor,Joglar, Jesus,Clapes, Pere
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experimental part
p. 3808 - 3816
(2010/01/16)
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- Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6- dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: Synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-d-glucitol
-
1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6- dideoxy-d-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Li
- Malle, Birgitte M.,Lundt, Inge,Wrodnigg, Tanja M.
-
experimental part
p. 1779 - 1786
(2008/10/09)
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- Stereoselective synthesis of D-1-deoxynojirimycin and its stereoisomers
-
A stereoselective synthesis of D-l-deoxynojirimycin (1), D-1-deoxymannojirimycin (2), and D-1-deoxyallonojirimycin (3) was achieved via the regioselective and diastereoselective amination of anti-l,2-dibenzyl ether using chlorosulfonyl isocyanate (CSI), ring-closing metathesis, diastereoselective dihydroxylation, and the regioselective stereochemical inversion of the resulting diol.
- Kim, In Su,Lee, Ho Young,Jung, Young Hoon
-
p. 1787 - 1800
(2008/03/14)
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- 1,5-Anhydro-D-fructose as chiral building block: A novel approach to 1-deoxymannojirimycin
-
A novel six-step synthesis of 1-deoxymannojirimycin from 1,5-anhydro-D-fructose in 35% overall yield is reported. The key steps are nucleophilic piperidine ring formation and subsequent Lewis acid induced pyran ether cleavage. Georg Thieme Verlag Stuttgart.
- Maier, Peter,Andersen, Soren Moller,Lundt, Inge
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p. 827 - 830
(2007/10/03)
-
- Efficient and stereodivergent synthesis of deoxyimino sugars
-
Both cis- and trans-2-substituted-1,2,3,6-tetrahydro-pyridin-3-ols have been prepared via an aldol condensation-ring-closing metathesis sequence. A stereodivergent synthesis of optionally functionalized deoxyimino sugars was achieved via asymmetric dihydroxylation or epoxidation/nucleophilic substitution of these tetrahydropyridines.
- Hong, Bor-Cherng,Chen, Zhong-Yi,Nagarajan, Arumugam,Kottani, Rudresha,Chavan, Vishal,Chen, Wei-Hung,Jiang, Yea-Fen,Zhang, Shuo-Cang,Liao, Ju-Hsiou,Sarshar, Sepehr
-
p. 2457 - 2468
(2007/10/03)
-
- Asymmetric synthesis of 1-deoxynojirimycin and its congeners from a common chiral building block
-
A new, promising chiral building block 9 for the synthesis of 1-deoxy-4,5-trans-oriented azasugars such as 1-deoxynojirimycin (1) was prepared in only four steps from the Garner aldehyde 10 using catalytic ring-closing metathesis (RCM) for the construction of the piperidine ring. In practical test, the first synthesis of all four isomers (1 and 6-8) of trans-4,5-orientated 1-deoxyiminosugars using 9 as a common chiral building block was demonstrated. Graphical Abstract
- Takahata, Hiroki,Banba, Yasunori,Sasatani, Mayumi,Nemoto, Hideo,Kato, Atsushi,Adachi, Isao
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p. 8199 - 8205
(2007/10/03)
-
- A General Synthesis of Iminosugars
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1-Deoxynojirimycin, 1-deoxymannojirimycin, and 1-deoxygalactostatin have been synthesized by epoxidation of tri-O-acetyl-6-deoxyhex-5-enopyranosyl azides followed by methanolysis, deacetylation, and catalytic hydrogenation. 1,6-Dideoxygalactostatin was obtained by the reaction of 2,3,4-tri-O-acetyl-6-deoxy-β-L-arabino-hex-5-enopyranosyl azide with NIS in methanol followed by deacetylation and catalytic hydrogenation. The overall yields were 4.4-23.5% over seven to nine steps.
- McDonnell, Ciaran,Cronin, Linda,O'Brien, Julie L.,Murphy, Paul V.
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p. 3565 - 3568
(2007/10/03)
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- A simple access to the D-mannosidase inhibitor, 1-deoxymannojirimycin
-
Crystalline 1,3,4,5-tetra-O-acetyl-6-bromo-6-deoxy-keto-D-fructose was prepared by reaction of 1,3,4,5-tetra-O-acetyl-D-fructopyranose with triphenylphosphane dibromide in dichloromethane. Subsequent deprotection followed by reaction of the free 6-bromodeoxyfructofuranose with sodium azide in N,N-dimethylformamide furnished the corresponding 6-azidodeoxyketose. Catalytic hydrogenation led to 1-deoxymannojirimycin in 27% overall yield from 1,3,4,5-tetra-O-acetyl-D-fructopyranose. This access is simple, inexpensive, high-yielding and clearly suitable for multigram preparations.
- Spreitz, Josef,Stuetz, Arnold E.,Wrodnigg, Tanja M.
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p. 183 - 186
(2007/10/03)
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- Synthesis of D- and L-Deoxymannojirimycin via an Asymmetric Aminohydroxylation of Vinylfuran
-
(Equation Presented) The Sharpless catalytic asymmetric aminohydroxylation has been applied to 2-vinylfuran, producing β-hydroxyfurfurylamine 5a with enantioexcess of >86% and 21% yield from furfural. The Cbz and TBS protected amino alcohol 5a was converted into both the D- and L-isomers of deoxymannojirimycin (DMJ) and deoxygulonojirimycin in five to seven steps and 48% and 66% overall yields. The key steps include the use of an aza-Achmatowicz reaction, a diastereoselective Luche reduction, diastereoselective dihydroxylation, and a tandem Cbz deprotection/reductive amination.
- Haukaas, Michael H.,O'Doherty, George A.
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p. 401 - 404
(2007/10/03)
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- Enantiopure 2,3-dihydro-4-pyridones as synthetic intermediates: Asymmetric synthesis of 1-deoxynojirimycin
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An asymmetric synthesis of 1-deoxynojirimycin (2) mediated by a chiral auxiliary is reported. The dihydropyridone 4 was converted to diol 11 in three steps by acetoxylation, hydrolysis, and stereoselective reduction. Dihydroxylation of 11 followed by catalytic reduction afforded 2.
- Comins, Daniel L,Fulp, Alan B
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p. 6839 - 6841
(2007/10/03)
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- Novel synthesis of the glycosidase inhibitor deoxymannojirimycin and of a synthetic precursor D-lyxo-hexos-5-ulose
-
Equation presented The synthesis of D-lyxo-hexos-5-ulose (5-ketomannose, 1,5-dicarbonyl sugar), a synthetic precursor to the glycoprocessing inhibitor deoxymannojirimycin, was carried out by an in situ epoxidation and hydrolysis of a trimethylsilyl-protected 6-deoxyhex-5-enopyranoside followed by facile removal of the protecting groups. A novel nine-step synthesis of deoxymannojirimycin has also been achieved from methyl α-D-mannopyranoside; this involved methanolysis of epoxides derived from an acetylated 1-azido-6-deoxyhex-5-enopyranoside followed by deprotection and catalytic hydrogenation.
- O'Brien, Julie L.,Tosin, Manuela,Murphy, Paul V.
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p. 3353 - 3356
(2007/10/03)
-
- New entry for asymmetric deoxyazasugar synthesis: Syntheses of deoxymannojirimycin, deoxyaltrojirimycin and deoxygalactostatin
-
Deoxyazasugars such as deoxymannojirimycin, deoxyaltrojirimycin and deoxygalactostatin were stereoselectively synthesized starting from (R)-(+)-4-methoxycarbonyloxazolidinoe via a bicyclic oxazolidinylpiperidine as a common synthetic intermediate.
- Asano, Koji,Hakogi, Toshikazu,Iwama, Seiji,Katsumura, Shigeo
-
-
- Simple synthetic route to polyhydroxylated pyrrolidines and piperidines
-
A short and simple synthetic route to polyhydroxylated piperidines and pyrrolidines were described with D-glucurono-δ-lactone as chiral educt. Key reaction steps included selective cleavage of terminal isopropylidene group of compound 12 with Dowex 50W-X8 resin (H+ form), regioselective ring opening of epoxide 16 and intramolecular nucleophilic amination of compound 14 and 18.
- Lee, Sang Gyeong,Park, Ki Hun,Yoon, Yong-Jin
-
p. 711 - 715
(2007/10/03)
-
- Chemical transformation of a 1-deoxynojirimycin derivative into 1-deoxymannojirimycin and 1-deoxygalactostatin
-
Treatment of 2,3-di-O-benzyl-N-benzyloxycarbonyl-6-O-t-butyldiphenylsilyl-1,5-dideoxy-1,5- imino-D-glucitol (4) with sodium hydride resulted in an intramolecular cyclization concomitant with silyl migration, giving the carbamate derivative 5 in good yield. This was efficiently converted into 1-deoxymannojirimycin (2) via regioselective p-toluenesulfonylation followed by an inversion reaction at the C-2 position. On the other hand, the monochloromethylsulfonate 10 obtained from 4 underwent configurational change at the C-4 position by the action of sodium benzoate. The resulting benzoate 11 was deprotected to afford 1-deoxygalactostatin (3).
- Takahashi, Shunya,Kuzuhara, Hiroyoshi
-
p. 117 - 128
(2007/10/03)
-
- Total synthesis of polyhydroxylated piperidine and pyrrolidine : Expect as glucosidase inhibitor
-
A new method for preparation of optically active (-)-deoxymannojirimycin (3) and 2R,5S-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (13) based on regioselective epoxide ring opening of 2-tert-butoxycarbonylamino-2-deoxy-3,4-O-isopropylidene-5,6-epoxy-D-glucitol (12) by intramolecular nucleophilic amination has been described.
- Lee, Sang Gyeong,Yoon, Yong-Jin,Shin, Sung Chul,Lee, Bu Yong,Cho, Su-Dong,Kim, Sung Kyu,Lee, Ji-Hyun
-
p. 701 - 706
(2007/10/03)
-
- A new approach to 1-deoxy-azasugars: Asymmetric synthesis of 1-deoxymannojirimycin and 1-deoxyaltronojirimycin
-
A concise and flexible method, based upon the kinetic resolution of racemic α-furfuryl amine derivatives, for the asymmetric synthesis of 1-deoxy-azasugars is described. (-)-1-Deoxymannojirimycin 1a has been synthesized in nine steps (5.8% overall yield) from the α-furfurylamine derivative 3 and its enantiomer (+)-1-deoxymannojirimycin 1b has been similarly synthesized in nine steps (3.7% overall yield) from (S)-3. (-)- and (+)-1-Deoxyaltronojirimycin, 16a and 16b, have also been synthesized in five steps (overall yields 21.5% and 25.4%, respectively) from the intermediates 9a and 9b, respectively.
- Xu, Yi-Ming,Zhou, Wei-Shan
-
p. 741 - 746
(2007/10/03)
-
- Synthesis of azasugars as potent inhibitors of glycosidases
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A series of enantiomerically pure azasugars (2,5-dideoxy-2,5-imino-D-mannitol, 1-deoxynojirimycin, 1-deoxymannojirimycin, and related compounds) was synthesized from D-mannitol via aminoheterocyclization of C2-symmetric bis-epoxides and subsequently followed by ring isomerization in few cases. These compounds have been evaluated as inhibitors of several glycosidases (α- and β-D-glucosidases, α-D-mannosidase and α-L-fucosidase). Inhibition studies indicate notably that the polyhydroxylated azepanes are inhibitors of glycosidases, with K(i) in the micromolar range.
- Le Merrer, Yves,Poitout, Lydie,Depezay, Jean-Claude,Dosbaa, Isabelle,Geoffroy, Sabine,Foglietti, Marie-Jose
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p. 519 - 533
(2007/10/03)
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- A new approach to 1-deoxy-azasugars: Asymmetric synthesis of deoxymannojirimycin
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A concise and flexible method based upon the kinetic resolution of the α-furfurylamine derivative (3) for asymmetric synthesis of 1-deoxy-azasugars has been provided and deoxymannojirimycin (2) has been synthesized.
- Xu, Yi-Ming,Zhou, Wei-Shan
-
p. 1461 - 1462
(2007/10/03)
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- Synthesis of azasugars. Part 1. Isomerization of polyhydroxylated piperidines
-
N-Benzyl-3,4-di-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol and L-gulitol undergo easy isomerization, mainly either by ring contraction, or either by SN2 inversion at C2. This isomerization performed by bis-hydroxyl activation allows to access to 2,5-dideoxy-2,5-imino-L-iditol, 5-epi-DNJ, DMDP, and DMJ.
- Poitout,Le Merrer,Depezay
-
p. 1609 - 1612
(2007/10/03)
-
- Simple Synthesis of (-)-Deoxymannojirimycin and (2S,3R,4R,5R)-3,4,5-trihydroxypipecolic Acid via Regioselective Hydrolysis
-
A short and efficient synthesis of (-)-deoxymannojirimycin and (2S,3R,4R,5R)-3,4,5-trihydroxypipecolic acid is described with D-glucono-δ-lactone as chiral educt.Key transformations included selective cleavage of a terminal isopropylidene group with Dowex 50W-X8 (H+) and intramolecular nucleophilic amination.
- Park, Ki Hun,Yoon, Yong Jin,Lee, Sang Gyeong
-
p. 2621 - 2624
(2007/10/02)
-
- Expeditious synthesis of azasugars by the double reductive amination of dicarbonyl sugars
-
Polyhydroxylated pyrrolidines and piperidines were prepared by the double reductive amination of dicarbonyl sugars with primary amines and NaCNBH3 in MeOH. Stereocontrol in these reactions depended on the nature of the amine and dicarbonyl sugar. For example, 5-keto-D-fructose (7) gave three pyrrolidine stereoisomers, with the N-alkylated 2,5-anhydro-2,5-imino-D-glucitol predominating. Under similar reaction conditions with benzhydrylamine, 5-keto-D-glucose (20) afforded a 96:4 mixture of piperidines favoring D-gluco 25A, whereas 5-keto-D-mannose (6) produced a 67:33 mixture enriched in D-manno isomer 40. This method allowed for the direct and relatively short synthesis of 1-deoxynojirimycin (DNJ, 1) and 1-deoxymannojirimycin (DMJ, 5) and N-alkylated derivatives thereof. Similar reactions with O-protected 5-keto-D-glucose derivatives 21 and 22 were less stereoselective and lower yielding.
- Baxter,Reitz
-
p. 3175 - 3185
(2007/10/02)
-
- A short practical synthesis of deoxymannojirimycin fromD-fructose
-
D-Fructose has been converted via sulfonate (10) and azides (11) and (12) into deoxymannojirimycin (1).
- Furneaux, Richard H.,Tyler, Peter C.,Whitehouse, Lynley A.
-
p. 3613 - 3616
(2007/10/02)
-
- A Simple Convergent Synthesis of the Mannosidase Inhibitor 1-Deoxymannonojirimycin from Sucrose
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The glycosidase inhibitor 1-deoxymannonojirimycin (1,5-dideoxy-1,5-imino-D-mannitol) was synthesized in four simple steps from sucrose via 6,6'-diazido-6,6'-dideoxysucrose and 6-azido-6-deoxy-D-fructofuranose.The "isomeric ballast" of the sequence, 6-azido-6-deoxy-D-glucose, could be partially converted into 6-azido-6-deoxy-d-fructofuranose with the aid of glucose isomerase (E.C. 5.3.1.5) demonstrating a novel synthetic application of this enzyme.The sequence allows access to multigramm quantities of 1-deoxy-mannonojirimycin in over 30percent overall yield without the need for expensive reagents and protecting group manipulations.Key Words: 1-deoxymannonojirimycin, mannosidase inhibitor, glucose isomerase, sucrose, synthesis
- Raadt, Anna de,Stuetz, Arnold E.
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p. 189 - 192
(2007/10/02)
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- Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus
-
Streptomyces subrutilus ATCC 27467, when grown on a glucose-containing soyabean medium, produces both 1-deoxymannonojirimycin (DMJ) and 1-deoxynojirimycin (DNJ) in its culture medium. When 1- or 2-[2H]-D-glucose is used, the deuterium label appears at C6 in both alkaloids and the labelling pattern suggests that the first step in the biosynthesis of both DNJ and DMJ is a glucose to fructose isomerisation. Studies with 5-2H]- and 6,6-2H2-D-glucose indicate that oxidation of the 6-position of the glucose/fructose occurs during the biosynthesis and that mannonojirimycin is the first aminosugar to be formed. Mannonojirimycin can then undergo dehydration and reduction to DMJ. Alternatively, epimerisation of mannonojirimycin can occur at C2 to give nojirimycin which is then dehydrated and reduced to DNJ.
- Hardick, David J.,Hutchinson, David W.,Trew, Sally J.,Wellington, Elizabeth M. H.
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p. 6285 - 6296
(2007/10/02)
-
- Aldolase-Catalyzed C-C Bond Formation for Stereoselective Synthesis of Nitrogen-Containing Carbohydrates
-
Rabbit muscle aldolase was found to catalyze stereoselective aldol addition of dihydroxyacetone phosphate (1) to 3-azido-2-hydroxypropanal (2).The ketose 1-phosphates were isolated as barium salts, 4a/4b, and hydrolyzed with acid phosphatase.The mixture of 6-azido-6-deoxy-D-fructose (5) and 6-azido-6-deoxy-L-sorbose (6) thus obtained was separated by anion exchange chromatography.Reductive amination of 5 and 6 yielded, respectively, 1-deoxymannojirimycin (7) and 1-deoxynojirimycin (8), with high diastereoselectivity (>98:2).Analogous aldol addition of 1 to 3-azido-2-hydroxybutanal (9) (E:Z=92:8) afforded a mixture of the 6-azido-6,7-dideoxyheptuloses 12 and 13, which contained 88percent of 6-azido-6,7-dideoxy-D-altro-heptulose (13).After anion-exchange chromatography, 13 was isolated as a 18:82 mixture of the α/β anomers.Reductive amination of pure 13 gave a mixture of 2,6,7-trideoxy-2,6-imino-D-glycero-D-manno- and D-gluco-heptitols (14 and 15) (3:2 molar ratio), which likewise was separated by anion-exchange chromatography.If a mixture of 12 and 13 was hydrogenated under identical conditions, 2,6,7-trideoxy-2,6-imino-L-glycero-L-gulo-heptitol (16) could be isolated besides 14 and 15.
- Straub, Alexander,Effenberger, Franz,Fischer, Peter
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p. 3926 - 3932
(2007/10/02)
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- Use of a recombinant bacterial fructose-1,6-diphosphate aldolase in aldol reactions: Preparative syntheses of 1-deoxynojirimycin, 1-deoxymannojirimycin, 1,4-dideoxy-1,4-imuno-D-arabinitol, and fagomine
-
A combined enzymatic aldol condensation and catalytic intramolecular reductive amination has been used in the high-yield asymmetric synthesis of polyhydroxylated alkaloids including 1-deoxynojirimycin, 1-deoxymannojirimycin, 1,4-dideoxy-1,4-imino-D-arabinitol, and fagomine. The Escherichia coli Zn2+-containing fructose-1,6-diphosphate aldolase overexpressed in E. coli was used for the syntheses. The enzyme in aqueous solution containing 0.3 mM ZnCl2 has excellent stability with a half-life of 60 days, compared to 2 days for the enzyme from rabbit muscle. The reactions were carried out under mild conditions without protection of functional groups. Either dihydroxyacetone phosphate or a mixture of dihydroxyacetone and inorganic arsenate can be used as donor in the aldol reactions. The aldol acceptors (R)- and (S)-3-azido-2-hydroxypropanal were prepared via lipase-catalyzed resolution of the racemic acetal precursor.
- Von Der Osten,Sinskey,Barbas III,Pederson,Wang,Wong
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p. 3924 - 3927
(2007/10/02)
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- A PRACTICAL SYNTHESIS OF DEOXYMANNOJIRIMYCIN AND OF (2S,3R,4R,5R)-3,4,5-TRIHYDROXYPIPECOLIC ACID FROM D-GLUCOSE
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Deoxymannojirimycin may be prepared in moderate amounts in an overall yield of 35percent in ten steps from diacetone glucose; the key step is formation of the piperidine ring by intramolecular nucleophilic displacement of a triflate at C-2 of a methyl glucofuranoside by a nitrogen function at C-6, irrespective of the anomeric configuration of the sugar.A synthesis of (2S,3R,4R,5R)-3,4,5-trihydroxypipecolic acid is reported.
- Fleet, George W. J.,Ramsden, Nigel G.,Witty, David R.
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p. 327 - 336
(2007/10/02)
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- Method for synthesis of deoxymannojirimycin
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A method is disclosed for the chemical synthesis of 1,5-dideoxy-1,5-imino-D-mannitol or 1,5-dideoxy-1,5-imino-L-mannitol from, respectively, 2,3-O-isopropylidene-L-gulono-γ-lactone or 2,3-O-isopropylidene-D-gulono-γ-lactone which comprises carrying out interconversion between the L-gulono and D-mannono forms or between the D-gulono and L-mannono forms, respectively, and connecting of C-1 to C-5 by nitrogen.
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- PRACTICAL SYNTHESIS OF DEOXYMANNOJIRIMYCIN AND MANNONOLACTAM FROM L-GULONOLACTONE. SYNTHESIS OF L-DEOXYMANNOJIRIMYCIN AND L-MANNONOLACTAM FROM D-GULONOLACTONE.
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An eight step synthesis of deoxymannojirimycin from L-gulonolactone in 25percent overall yield is reported; the key step is the formation of a δ-lactam by the reduction of a 5-azidolactone.The preparations of mannonolactam from L-gulonolactone and of L-deoxymannojirimycin and L-mannonolactam from D-gulonolactone are described.
- Fleet, George W. J.,Ramsden, Nigel G.,Witty, David R.
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p. 319 - 326
(2007/10/02)
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- A COMBINED CHEMICAL AND ENZYMATIC PROCEDURE FOR THE SYNTHESIS OF 1-DEOXYNOJIRIMYCIN AND 1-DEOXYMANNOJIRIMYCIN
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1-Deoxynojirimycin and 1-deoxymannojirimycin have been prepared via fructose diphosphate aldolase catalysed condensation followed by catalytic intramolecular reductive amination.
- Pederson, Richard L.,Kim, Mahn-Joo,Wong, Chi-Huey
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p. 4645 - 4648
(2007/10/02)
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- SHORT SYNTHESES OF D-DEOXYMANNOJIRIMYCIN AND D-MANNOLACTAM FROM L-GULONOLACTONE AND OF L-DEOXYMANNOJIRIMYCIN AND L-MANNONOLACTAM FROM D-GULONOLACTONE
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Short syntheses of D-deoxymannojirimycin and of D-mannolactam from L-gulonolactone are reported; identical sequences on D-gulonolactone lead to L-deoxymannojirimycin and L-mannolactam.
- Fleet, George W. J.,Ramsden, Nigel G.,Witty, David R.
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p. 2871 - 2874
(2007/10/02)
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- SYNTHESIS OF DEOXYMANNOJIRIMYCIN FAGOMINE DEOXYNOJIRIMYCIN 2-ACETAMIDO-1,5-IMINO-1,2,5-TRIDEOXY-D-MANNITOL 2-ACETAMIDO-1,5-IMINO-1,2,5-TRIDEOXY-D-GLUCITOL 2S,3R,4R,5R-TRIHYDROXYPIPECOLIC ACID AND 2S,3R,4R,5S-TRIHYDROXYPIPECOLIC ACID FROM METHYL 3-O-BENZYL-2,6-DIDEOXY-2,6-IMINO-α-D-...
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The value of methyl 3-O-benzyl-2,6-dideoxy-2,6-imino-α-D-mannofuranoside as a divergent intermediate for the preparation of polyhydroxylated piperidines is illustrated by the synthesis of deoxymannojirimycin (1,5-dideoxy-1,5-imino-D-mannitol), fagomine (1,5-imino-1,2,5-trideoxy-D-arabino-hexitol), deoxynojirimycin (1,5-dideoxy-1,5-imino-D-glucitol), 2-acetamido-1,5-imino-1,2,5-trideoxy-D-mannitol, 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol, 2S,3R,4R,5R-trihydroxypipecolic acid and 2S,3R,4R,5S-trihydroxypipecolic acid.
- Fleet, George W. J.,Fellows, L. E.,Smith, Paul W.
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p. 979 - 990
(2007/10/02)
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- Synthesis of the antibiotic 1,5-dideoxy-1,5-imino-D-glucitol; concomitant formation of the D-mannitol analogue
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The easy accessible 1,2-O-isopropylidene-3-O-benzyl-α-D-glucofuranose was converted in six steps into 1,2-O-isopropylidene-3,6-di-O-benzyl-5-deoxy-5-azido-α-D-glucofuranose.The latter afforded, after acidolysis followed by hydrogenolysis, 1-deoxynojirimicine and a small quantity of 1-deoxymannonojirimicine.The antibiotic thus obtained had an inhibitory effect on the trimming of N-linked carbohydrates in IgM.
- Broxterman, H. J. G.,Marel, G. A. van der,Neefjes, J. J.,Ploegh, H. L.,Boom, J. H. van
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p. 571 - 576
(2007/10/02)
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- SYNTHESIS OF 5-AMINO-5-DEOXY-D-MANNOPYRANOSE AND 1,5-DIDEOXY-1,5-IMINO-D-MANNITOL, AND INHIBITION OF α- AND β-D-MANNOSIDASES
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The title compounds and the corresponding L-gulo derivatives were synthesised in 6 steps from benzyl 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside.The Ki values, determined from inhibition studies with α-D-mannosidases from jack beans, almonds, and calf liver, and β-D-mannosidase from Aspergillus wentii, ranged from 70 to 400 μM for the mannitol derivative and from 1.2 to 20 μM for 5-amino-5-deoxy-D-mannopyranose, i.e., inhibition is E2-E4-fold stronger than with D-mannose.Marked enhancement of inhibition with increasing pH is ascribed to the ionisation of a carboxyl group at the active site, forming an ion pair with the protonated inhibitor.The inhibition equilibrium between the jack-bean enzyme and the mannose derivative was approached slowly with kapp 2.0E5 M-1.min-1.The mannose-derived inhibitor was also inhibitory against β-D-glucosidases from almonds and Asp. wentii, with Ki values only 20-150-times larger than those for the inhibition of these enzymes by 5-amino-5-deoxy-D-glucopyranose.This moderate discrimination in binding of D-gluco and D-manno derivatives is in marked contrast to the high specificity shown by the glucosidase in catalysing the hydrolysis of mannosidases.A similar low specificity with respect to binding, combined with highly specific catalysis, was also seen with the mannosidases acting on inhibitors and substrates with the D-gluco configuration.
- Legler, Guenter,Juelich, Elisabeth
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- SYNTHESES OF 1,5-DIDEOXY-1,5-IMINO-D-MANNITOL FROM D-MANNOSE AND D-GLUCOSE
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Unambigous enantiospecific syntheses of 1,5-dideoxy-1,5-imino-D-mannitol (LU1, 1-deoxy-mannojirimycin) are reported (i) from D-mannose via hydrogenation of a 5-azido-5-deoxy mannose, and (ii) from D-glucose, in which the key step involves nucleophilic substitution of a trifluoromethanesulphonyl group from C-2 of D-glucose.
- Fleet, G. W. J.,Gough, M. J.,Shing, T. K. M.
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p. 4029 - 4032
(2007/10/02)
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