Aza Sugars Research Articles

Microbial Oxidation of Aromatics in Enantiocontrolled Synthesis. 2. Rational Design of Aza Sugars (endo-Nitrogenous). Total Synthesis of (+)-Kifunensine, Mannojirimycin, and Other Glycosidase Inhibitors

A general method of synthesis for lactones and lactams related to carbohydrates has been developed that relies on the biocatalyticgeneration of 1-chloro-2,3-dihydroxycyclohexa-4,6-diene (l), obtained in excellent yield by fermentation of chlorobenzene with Pseudomonasputida 39D, followed by further functionalization to nitrogen-substituted cyclitols. These amino or azido cyclitols of type 15 are then subjected to controlled ozonolysis, which yields either lactones such as 27 or lactams containing five-membered (28) or six-membered (20 and 23) rings. Such compounds are useful intermediates for the preparation of aza sugars. Mannojirimycin (84 has been synthesized in seven steps from chlorobenzene. Kifunensine (7) has been prepared in 11 steps from chlorobenzene following an intersection with Hashimoto's procedure. Full experimental and spectral details are provided for all compounds. The potential of this general method and implications of the disclosed design features in the field of amino sugar and aza sugar synthesis are indicated.

Expeditious Synthesis of Aza sugars 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 NaCNBH 3 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 stereoselectivite and lower yielding

Synthesis of oxygen‐substituted N‐alkyl 1‐deoxynojirimycin derivatives: Aza sugar α‐glucosidase inhibitors showing antiviral (HIV‐1) and immunosuppressive activity

AbstractThe synthesis of a series of six less‐lipophilic analogues of the α‐glucosidase inhibitor N‐decyl‐1‐deoxynojirimycin (N‐decyl‐dNM, 5) is described. With the incorporation of a single oxygen atom, particularly at position seven in the N‐decyl side‐chain to give N‐(7‐oxadecyl)‐dNM (8), the therapeutic ratio (α‐glucosidase I inhibitory activity over toxicity in HepG2 cells) increases considerably. Compound 8 inhibits purified porcine liver α‐glucosidase I with an IC50 value of 0.28 μM. The position of the oxygen atom in the N‐decyl side‐chain is of importance since N‐(3‐oxadecyl)‐dNM (7) is less active than 8 and, moreover, is toxic to HepG2 cells at 3 mM. Subsequently, the synthesis of eight ester derivatives of N‐(7‐oxadecyl)‐dNM is described. All of these ester analogues are less active α‐glucosidase inhibitors than the parent compound 8 in HepG2 cells. The compounds were further analyzed for antiviral and immunomodulatory activity in vitro. It is found that the most potent α‐glucosidase I inhibitor from this study N‐(7‐oxadecyl)‐dNM (8) inhibits HIV‐1‐induced syncytia formation and lymphocyte proliferation in vitro. Finally, compound 8 was investigated in vivo. N‐(7‐Oxadecyl)‐dNM (8) reduced adjuvant‐induced arthritis in rats making this compound a potential candidate for treating autoimmune diseases like rheumatoid arthritis.

ChemInform Abstract: Flexible and Stereocontrolled Synthesis of Aza Sugars with Novel Substitution Patterns.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A New Procedure for the Synthesis of Aza Sugars.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Enzyme‐Catalyzed Organic Synthesis: Practical Routes to Aza Sugars and Their Analogues for Use as Glycoprocessing Inhibitors

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Chemo‐Enzymatic Synthesis of Five‐Membered Aza Sugars as Inhibitors of Fucosidase and Fucosyltransferase: An Issue Regarding the Stereochemistry Discrimination at Transition States.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Rational Design of Aza Sugars via Biocatalysis: Mannojirimycin and Other Glycosidase Inhibitors.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Total, Asymmetric Synthesis of Glycosidase Inhibitors such as the Aza Sugars, Castanospermine and Analogs, from Furan

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Rational design of aza sugars via biocatalysis: mannojirimycin and other glycosidase inhibitors

Summary: Mannojirymicin 2a, its C-5 epimer 13, and mannosidase inhibitor 3a have been synthesized from chlorobenzene via enzymatic hydroxylation followed by stereoselective amination and oxidative cleavage of the l-chlorocyclohexa-4,S-diene-2,3-diol. Compounds that selectively inhibit glycosidases have attracted interest because of the significance of such inhibition to both viral expression' and tumor growth.2 The synthesis of nojirimycin derivatives 1, mannojirimy- cine 2, and the five-membered am sugars 3 have been X X X X HN + HNZH HNFH OH r-/c.. OH 'OH OH -OH +OH bH laX.0 2ax.0 3~x10 lb X = H2 2b X a Hz 3aX.O 3dx.H~ 3b X = Hz accomplished by numerous approaches from either car- bohydrates or other naturally occurring compounds3 by employing aldolaees4 or by combination of microbial oxidation with chemical ~ynthesis.~ As a part of a biocatalysis program directed at an exhaustive and general synthesis of monosaccharides of any stereomeric or enantiomeric constitution,alb we became interested in a similar general approach to aza sugars of type

Chemo-enzymatic synthesis of five-membered azasugars as inhibitors of fucosidase and fucosyltransferase: An issue regarding the stereochemistry discrimination at transition states

Three new 5-membered aza sugars which inhibit bovine α-fucosidase with Ki values in the μM range have been prepared based on aldolase reactions.

Practical synthesis of carbohydrates based on aldolases and glycosyl transferases

Abstract

ChemInform Abstract: Palladium‐Mediated Stereocontrolled Reductive Amination of Azido Sugars Prepared from Enzymatic Aldol Condensation: A General Approach to the Synthesis of Deoxy Aza Sugars.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Palladium-mediated stereocontrolled reductive amination of azido sugars prepared from enzymic aldol condensation: a general approach to the synthesis of deoxy aza sugars [Erratum to document cited in CA115(13):136547j

Palladium-mediated stereocontrolled reductive amination of azido sugars prepared from enzymic aldol condensation: a general approach to the synthesis of deoxy aza sugars [Erratum to document cited in CA115(13):136547j

Use of dihydroxyacetone phosphate-dependent aldolases in the synthesis of deoxy aza sugars

Use of dihydroxyacetone phosphate-dependent aldolases in the synthesis of deoxy aza sugars

Palladium-mediated stereocontrolled reductive amination of azido sugars prepared from enzymic aldol condensation: a general approach to the synthesis of deoxy aza sugars

Palladium-mediated stereocontrolled reductive amination of azido sugars prepared from enzymic aldol condensation: a general approach to the synthesis of deoxy aza sugars