Synthesis of C-glycosyl β-amino acids by asymmetric Mannich-type three-component reactions

C-Galactosyl and C-ribosyl β-amino acids were prepared by one-pot InCl₃-catalyzed Mannich-type three-component condensation (3CC) by combining the corresponding formyl C-glycoside, p-methoxybenzyl amine, and a ketene silyl acetal. In each case the reaction was highly stereoselective and afforded only one single product in good to excellent yields.     

A convenient microwave-assisted synthesis of N-glycosyl amino acids

Optimization of coupling reactions of glycosylamines with Fmoc-protected aspartic acid, by microwave approach, is described. Different reaction conditions, quantities of substrates and solvents were tested to develop simple and reproducible methodologies. The best results were obtained using new triazine-based coupling reagents with a monomode microwave Discover® BenchMate™ instrument (CEM). The N-glycosyl amino acids were then deprotected to achieve final products for SPPS.     

The preparation of C-glycosyl amino acids—an examination of olefin cross-metathesis

A study investigating the structural features directing olefin cross-metathesis to afford C-glycoamino acids was carried out. These results lead to an appreciation of the importance of proximal functionality to the relative reactivity of olefins in metathesis reactions providing a variable that is useful to suppress undesirable self-metathesis.     

Asymmetric bioreductions of beta-nitro acrylates as a route to chiral beta2-amino acids

[Structure: see text] Reductions of beta-nitroacrylates by Saccharomyces carlsbergensis old yellow enzyme is the key step in a concise route to optically active beta2-amino acids. The enzymatic reductions occur with 87-96% ee, with larger substrates providing greater stereoselectivities. This work extends enantioselective enzymatic alkene reductions to include acyclic systems with weakly coordinating substituents.     

The stereoselective synthesis of C-linked 4′-deoxy aza-disaccharides from C-linked carbo-β-amino acids

The stereoselective synthesis of 4′-deoxy aza-disaccharides in a concise and practical approach is described from C-linked carbo-β-amino acid esters and this protocol utilizes an intramolecular amide bond formation and cis-dihydroxylation for the construction of the new sugar ring.     

The hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron-rich alkenes as a route to unnatural α-amino acids

A new method for the stereoselective synthesis of nonproteinogenic α-amino acids has been developed, which involves hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron-rich alkenes, such as enol ethers, enamines and allylsilanes, and a further two or three step manipulation of the resulting oxazines.     

A convenient synthetic route to enantiopure N-tosylazetidines from α-amino acids

A general and convenient synthetic route to various chiral 2-substituted- and 2,4-disubstituted-N-tosylazetidines (ee >99%) is described in good overall yields starting from chiral α-amino acids using very simple chemistry.     

Efficient access to disubstituted exo-glycals. Application to the preparation of C-glycosyl compounds

Efficient methods of preparation of disubstituted exo-glycals by palladium cross-coupling reaction on the readily available dibromo exo-glycal and methoxycarbonyl exo-glycal have been developed. Hydrogenation of these new monosubstituted and disubstituted exo-glycals proceeded with a high stereocontrol and led to original C-glycosyl compounds.     

Azidation of anomeric nitro sugars: application in the synthesis of spiroaminals as glycosidase inhibitors

6,5-Fused sugar-derived spiroaminals have been synthesized from the azido esters obtained via the nucleophilic substitution reactions of unstable Michael adducts derived from 1-nitro sugars. Most of the spiroaminals synthesized showed moderate but selective inhibitory activities toward some glycosidases.     

Synthesis of S-glycosyl amino acids and S-glycopeptides via photoinduced click thiol-ene coupling

We report on the photoinduced addition of glycosyl thiols to alkenyl glycines (thiol-ene coupling) to give S-glycosyl amino acids in high yields (53-90%). One of the amino acids thus prepared was used in the construction of a tripeptide via solution phase chemistry. Moreover, a one-pot two-step approach to an S-glycopeptide was developed using glutathione (GSH) as model starting material. This approach involved GSH S-alkenylation followed by photoinduced hydrothiolation by a glycosyl thiol.     

A synthetic route to enediyne-bridged amino acids

A general strategy for the preparation of enediyne-bridged amino acids has been disclosed. A cross-coupling reaction between amino- and carboxyl-modified amino acids under Sonogashira reaction conditions gave a protected enediyne-peptide conjugate. The model obtained can be used as a template in studies of Bergman cycloaromatization or peptide conformational preferences induced by the presence of the enediyne moiety.     

Enantioselective organocatalytic route to trifluoromethyl-β-amino acids using chiral bases

Herein are studied new aspects of enantioselective (1,3) proton transfer of ethyl-4,4,4-trifluoroacetoacetate (ETFAA) amino derivatives. When catalyzed by an appropriate chiral base, ee's as high as 71% are observed. Special emphasis is given to mechanistic insights of the reaction by use of deuterated derivative. All results converge on a deprotonation as both rate and asymmetric determining step. This study opens a new route to trifluoromethylated chiral building blocks.     

Combinatorial approaches to iminosugars as glycosidase and glycosyltransferase inhibitors

Oligosaccharide processing enzymes such as glycosidases and glycosyltransferases are important classes of biocatalysts involved in synthesising specific oligosaccharide structures on proteins and lipids. These enzymes are known to be involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins, lysosomal catabolism of glycoconjugates and inter-cellular recognition events. Inhibition of these enzymes can disrupt biosynthesis of oligosaccharides, thus interfering in all of these processes. Hence, "glyco-enzyme" inhibitors might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes. This very important prospect has led to increasing interest and demand for these compounds. Interference in oligosaccharide processing is the basis for the anti-influenza neuraminidase inhibitors that have recently been marketed and also for the potential use of glycosidase inhibitors against HIV, Gaucher's disease, hepatitis, and cancer. Since a rational design and synthesis of inhibitors are often extremely difficult due to the limited information regarding the structure of the active site, combinatorial approaches are particularly promising. This review will focus on synthetic efforts for the preparation of combinatorial libraries of glyco-enzyme inhibitors.     

A route to long-chain amino sugars by three substituted thiazoles as auxiliaries: thiazole-2-carbonitrile n-oxide, 2-trimethylsilylthiazole,and 2-thiazolylmethylenetriphenyl-phosphorane

The nitrile oxide-furan cycloadduct thiazole furoisoxazoline 4a is transformed into the 5-amino-5-deoxy dialdoidofuranose derivative 8 through selective elaboration of the three heterocyclic rings; i) bis-hydroxyalkylation of dihydrofuran carbon-carbon double bond; ii) reductive cleavage of the isoxazoline ring; iii) conversion of thiazole into formyl. One- and two-carbon chain extension of the resulting amino hexose by reaction with 2-trimethylsilylthiazole and 2-thiazolylmethylenetriphenyl-phosphorane respectively affords C₇ and C₈ homologues.     

Gold-catalyzed intramolecular hydroamination of α-amino allenamides as a route to enantiopure 2-vinylimidazolidinones

An efficient gold-catalyzed procedure for the preparation of 2-vinylimidazolidinones has been developed. The starting materials for the synthesis of these compounds are α-amino allenamides which undergo heterocyclization by means of nucleophilic attack of the amino group on the inside double bond of the 1,2-diene moiety. This is the first example of a gold-catalyzed cyclization on allene substrates bearing an amido group which, however, resulted inactive.     

Nitrogen Alkylation of schiff bases and amidines as a route to N-alkyl amino acids

Schiff base and amidine ester $\text{3}$ are alkylated and then hydrolyzed to yield N-alkyl amino acids $\text{4}$ in 41–75% yield with high to complete retention of optical activity.     

Synthesis of all diastereomeric methyl 2,5-anhydro-3-deoxy-hexonates: precursors to C-2-deoxynucleosides and THF-templated γ- and δ-amino acids

Efficient syntheses of all diastereomers of methyl 2,5-anhydro-3-deoxy-hexonate from mannono- or gulono-lactones provide precursors for C-nucleosides of 2-deoxyribose and for THF-templated γ- and δ-amino acids.     

The epimetallation and carbonation of carbonyl and imino derivatives: Epivanadation route to 2-amino and 2-hydroxy acids

The feasibility of hydrocarboxylating carbonyl and imino derivatives by the two-step process of epimetallation and carbonation has been demonstrated with the model substrates of 9-fluorenone and 9-fluorenone anil. With lithium vanadium dihydride as the epimetallating agent, such hydrocarboxylation has led to a 75% yield of 9-hydroxy-9-fluorenecarboxylic acid and a 65% yield of 9-(N-phenylamino)-9-fluorenecarboxylic acid, respectively. Some initial success in extending the scope of this reaction to other substrates, such as benzophenone, has been achieved by using other epimetallating agents, like the presumed LiV(CH₃)₂ and Ti(OPrⁱ)₂. A brief review of the processes and organic synthetic applications of epimetallation and transfer epimetallation of C-C π-bonds is offered as background.