ABSTRACT
A simple, highly stereoselective one-pot methodology for the synthesis of novel 1,2-annulated sugars comprising of oxa-oxa and oxa-carbasugar fused skeletons from 2-nitrogalactal and a sugar-derived enone, obtained from 2-formylgalactal, promoted by KOtBu and CH3ONa respectively is described. Both processes rely on a domino double-Michael addition reaction resulting in the formation of three stereocenters in a single pot, including a quaternary center.
Subject(s)
Sugars/chemical synthesis , Crystallography, X-Ray , Cyclization , Models, Molecular , Molecular Conformation , Stereoisomerism , Sugars/chemistryABSTRACT
Six different types of O-benzyl protected proline derivatives have been synthesized from D-glycals and 2C-formyl-glycals. One of the di-O-benzyl protected proline derivatives has been utilized for the synthesis of polysubstituted pyrrolizidines via [3 + 2] cycloaddition in a stereoselective manner. Further, we also report on the stereoselective synthesis of biologically active 1C-aryl/alkyl pyrrolidines i.e. 4-epi-radicamine B, 4-epi-radicamine A, 1C-butyl and 1C-methyl pyrrolidines through double reductive amination of a variety of D-glucal derived diketones with p-methoxybenzylamine.
Subject(s)
Deoxyglucose/analogs & derivatives , Proline/chemical synthesis , Pyrroles/chemical synthesis , Deoxyglucose/chemistry , Molecular Structure , Proline/chemistry , Pyrroles/chemistryABSTRACT
A simple Pd(OAc)2 catalyzed strategy for the synthesis of sugar-fused indolines from 2-N-oxalylamido-2-deoxy-C-aryl glycosides is reported by utilizing N-oxalylamido group as an auxiliary via C(sp2)-H/NH Activation. The reaction is successfully applied on glucose as well as galactose derived differently substituted 2-N-oxalylamido-2-deoxy-C-aryl glycosides to give sugar-fused indolines in moderate to good yields. The utility of this strategy in the synthesis of sugar-fused indoles is also described.
Subject(s)
Carbon/chemistry , Glycosides/chemistry , Hydrogen/chemistry , Indoles/chemistry , Indoles/chemical synthesis , Palladium/chemistry , Carbohydrate Conformation , Catalysis , Chemistry Techniques, Synthetic , Models, MolecularABSTRACT
A highly efficient stereoselective synthesis of sugar fused 1,2-annulated isochromans is reported by utilizing the oxa-Pictet-Spengler cyclization reaction. The process is found to be very general as both glucal and galactal derived C2-hydroxy-α-C-aryl glycosides lead to the target molecules in good yields. The utility of this strategy was extended to the synthesis of sugar fused isochromanones, which are bergenin type molecules.
ABSTRACT
A simple, highly efficient and regiospecific method for the direct conversion of 3- O-benzylated as well as silylated glycals into the corresponding enones has been developed using PIFA-TEMPO and water reagent system. The reaction is scalable on a gram scale under mild conditions with a yield up to 86%.
ABSTRACT
2-Deoxy-ß-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization. The salient features of this methodology are high yields and excellent stereoselectivity. This method has also been successfully applied to the synthesis of differently protected 2-deoxy-ß-C-aryl glycosides and C-disaccharides. One of the 2-deoxy-ß-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
Subject(s)
Disaccharides/chemistry , Glycosides/chemistry , Glycosides/chemical synthesis , Chemistry Techniques, Synthetic , Cyclization , StereoisomerismABSTRACT
Synthesis of 1,2-annulated-C-aryl glycosides has been achieved in a stereoselective manner through the Diels-Alder reaction between carbohydrate-derived terminally unsubstituted dienes and in situ generated arynes. In these reactions, formation of sugar-fused (or branched) naphthalenes was also observed and found to be temperature dependent and thus constituting one of the salient features of this work. The synthetic importance of 1,2-annulated-C-aryl glycosides has been explored by transforming them into densely oxygenated products by functionalizing the unsubstituted exo-double bond. Further, 1,2-annulated-C-aryl glycosides give rapid access to C-aryl glycosides in four steps.
Subject(s)
Alkadienes/chemistry , Alkynes/chemistry , Carbohydrates/chemistry , Glycosides/chemical synthesis , Naphthalenes/chemical synthesis , Sugars/chemical synthesis , Glycosides/chemistry , Molecular Structure , Naphthalenes/chemistry , Stereoisomerism , Sugars/chemistryABSTRACT
An unprecedented water-mediated and TEMPO-catalyzed, one-step, highly regiospecific and stereoselective functionalization of glycals to 2-azido-2-deoxysugars has been developed using a PIFA-Me3SiN3 reagent system in the presence of Bu4NHSO4 as a phase-transfer catalyst. The method is metal-free, proceeds under mild reaction conditions, and tolerates a variety of protecting groups. Using this method, the synthesis of an important trisaccharide unit bound by the monoclonal anti-I Ma antibody has also been demonstrated.
ABSTRACT
Activation of sulfoxide as glycosyl donors using AuCl3/AgOTf reagent system has been described. Under optimal reaction conditions, both armed and disarmed glycosyl sulfoxide donors were found to react with a range of primary, secondary, and tertiary alcohol acceptors, and sugar derived glycosyl acceptors to afford the corresponding glycosides in moderate to good yields with predictable selectivity. The reactions are quick (20-60 min), facile at room temperature and the reactions conditions tolerate acid sensitive groups.
Subject(s)
Carbohydrate Biochemistry/methods , Glycosides/chemical synthesis , Gold Compounds/chemistry , Mesylates/chemistry , Sulfoxides/chemistry , Catalysis , Glycosides/chemistry , Glycosylation , TemperatureABSTRACT
A "Prins pinacol type rearrangement followed by C4-OBn participation" in a cascade manner has been observed while probing the fate of carbocation in some carbohydrate derived homoallylic alcohols in the Prins reaction. This has led to an easy access to tetrahydrofuran-fused bridged bicyclic ketals (or tetrahydrofuran-fused 1,6-anhydro-heptopyranose frameworks) which are further converted into some annulated sugars and C2-branched heptoses.
Subject(s)
Carbohydrates/chemical synthesis , Furans/chemical synthesis , Heptoses/chemical synthesis , Polycyclic Compounds/chemical synthesis , Carbohydrates/chemistry , Furans/chemistry , Heptoses/chemistry , Molecular Structure , Polycyclic Compounds/chemistry , StereoisomerismABSTRACT
Highly regioselective 1,3-dipolar cycloadditions between d-arabinose-derived nitrones and d-mannitol-derived trans-olefins have been utilized to synthesize isofagomine-pyrrolidine hybrid sugars, hydroxymethylated analogues of (-)-steviamine and analogues of (+)-hyacinthacine C5. All of the new compounds were subsequently tested against several commercially available glycosidases, and some of them showed good and selective glycosidase inhibition.
Subject(s)
Carbohydrates/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Imino Pyranoses/chemical synthesis , Imino Sugars/chemical synthesis , Indolizidines/chemical synthesis , Pyrrolidines/chemical synthesis , Pyrrolizidine Alkaloids/chemical synthesis , Carbohydrates/chemistry , Cycloaddition Reaction , Enzyme Inhibitors/chemistry , Glycoside Hydrolases/chemistry , Imino Pyranoses/chemistry , Imino Sugars/chemistry , Indolizidines/chemistry , Molecular Structure , Pyrrolidines/chemistry , Pyrrolizidine Alkaloids/chemistry , StereoisomerismABSTRACT
A general strategy for the synthesis of analogues of radicamine B has been carried out from D-mannitol. This method has been further extended to the synthesis of analogues of codonopsine and codonopsinine using appropriate Grignard reagents. The hence obtained molecules have been tested against various commercially available glycosidases and found to act as moderate to good inhibitors.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Mannitol/chemistry , Pyrrolidines/pharmacology , Enzyme Inhibitors/pharmacology , Pyrrolidines/chemical synthesisABSTRACT
A carbon-Ferrier rearrangement on glycals has been performed by using ceric ammonium nitrate to obtain products in moderate to good yields with high selectivity. The versatility of this method has been demonstrated by applying it to differently protected glycals and by employing several nucleophiles. The obtained C-allyl glycoside has been utilized for the synthesis of a orthogonally protected 2-amino-2-deoxy-C-glycoside.
ABSTRACT
An expedient one-step synthesis of 2-iodoglycals and 2-bromoglycals from glycals using NIS/AgNO3 and NBS/AgNO3 as reagent systems has been developed. The utility of these 2-haloglycals has been demonstrated by converting them into 2C-branched glycals via the Heck coupling reaction. Ferrier reaction of tri-O-acetyl-2-iodoglycals followed by Heck coupling reaction with methyl acrylate leads to 2C-branched O-glycosides.
Subject(s)
Glycosides/chemistry , Glycosides/chemical synthesis , Hydrocarbons, Brominated/chemistry , Hydrocarbons, Brominated/chemical synthesis , Hydrocarbons, Iodinated/chemistry , Hydrocarbons, Iodinated/chemical synthesis , Catalysis , Indicators and Reagents , Molecular Structure , Silver Nitrate/chemistry , Stereoisomerism , Succinimides/chemistryABSTRACT
A few bicyclic hybrid sugar molecules comprising of oxa-aza, oxa-oxa, and oxa-carbasugar fused skeletons were designed and synthesized from C-2 acetoxyglucal involving Ferrier rearrangement, Grignard addition, and ring-closing metathesis as key steps. The inhibitory activities of the synthesized molecules were tested against commercially available enzymes, which revealed the sugar-piperidine and sugar-pyran hybrids as potent and selective inhibitors.
Subject(s)
Aza Compounds/chemistry , Aza Compounds/pharmacology , Carbasugars/chemistry , Carbasugars/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Glycoside Hydrolases/chemistry , Oxides/chemistry , Oxides/pharmacology , Piperidines/chemistry , Pyrans/chemistryABSTRACT
Synthesis of dihydroxymethyl dihydroxypyrrolidines from C-2 formyl D-glycals has been described via a common dicarbonyl intermediate. The hence obtained pyrrolidines have been further utilized for the synthesis of some steviamine analogues. The newly synthesized molecules have been evaluated for glycosidase inhibition against 6 commercially available enzymes and found to be active in the micromolar range, where one of the steviamine analogues showed good and selective inhibition of ß-mannosidase (Helix pomatia).
Subject(s)
Carbohydrates/chemistry , Enzyme Inhibitors/pharmacology , Imino Sugars/pharmacology , Indolizidines/pharmacology , Pyrrolidines/chemical synthesis , Pyrrolidines/pharmacology , beta-Galactosidase/antagonists & inhibitors , Animals , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Helix, Snails/enzymology , Imino Sugars/chemical synthesis , Imino Sugars/chemistry , Indolizidines/chemical synthesis , Indolizidines/chemistry , Molecular Structure , Pyrrolidines/chemistry , Structure-Activity Relationship , beta-Galactosidase/metabolismABSTRACT
A reagent system comprising tetrabutylammonium nitrate-trifluoroacetic anhydride-triethylamine has been developed for the synthesis of 2-nitroglycals from various protected glycals. The base-catalyzed Ferrier rearrangement on tri-O-acetylated 2-nitroglycals has been reported for the first time. Reactivity of these nitroacetates and associated selectivity has been examined, and some of the products have been converted into 2,3-diamino-2,3-dideoxyglycosides and methyl N-acetyl-D-lividosaminide.
Subject(s)
Acetic Anhydrides/chemistry , Ethylamines/chemistry , Fluoroacetates/chemistry , Polysaccharides/chemical synthesis , Pyridines/chemistry , Quaternary Ammonium Compounds/chemistry , Acetylation , Catalysis , Molecular Structure , Polysaccharides/chemistryABSTRACT
The importance of glycosidase inhibitors and especially the bicyclic molecules has led to design and assessment of many analogs of naturally occurring molecules. This review focuses on the synthesis and enzyme inhibitions of a few selected (synthetic or non-naturally occurring) molecules that have been reported in the last decade, which allow one to draw some connection between varying the structural features and their effect on glycosidase inhibitions. It is expected that further improvements based on these features could lead to improved inhibitors.
Subject(s)
Azabicyclo Compounds/chemical synthesis , Carbasugars/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Azabicyclo Compounds/chemistry , Carbasugars/chemistry , Enzyme Inhibitors/chemistry , Glycoside Hydrolases/metabolism , Indolizidines/chemistry , Structure-Activity RelationshipABSTRACT
Synthesis of isofagomine has been achieved by implementation of aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a key step. The above rearrangement has also been utilized in the synthesis of biologically important polyhydroxylated piperidine frameworks such as isogalactofagomine, ent-isogalactofagomine and their analogues and some other azasugars as glycosidase inhibitors.
Subject(s)
Aza Compounds/chemistry , Carbohydrates/chemistry , Ether/chemistry , Imino Pyranoses/chemical synthesis , Hydroxylation , Methylation , Molecular StructureABSTRACT
Glycals have been transformed into a variety of functionalized substrates which have been found to be useful in synthesizing some aminosugars, N-glycopeptides, nitrosugars and some iminosugars which are potential glycosidase inhibitors. An account of work that has been done in our laboratory is briefly discussed here.
