Phosphite-based sialic acid donors in the synthesis of α(2→9) oligosialic acids

The combination of a phosphite donor and an anomeric thiocresol-protected acceptor, both with a TFA protecting group at C-5 of the sialic acid, provides good α-selectivity and yield in sialylation. Although the convergent synthetic strategy of using a phosphite disialo-donor and a disialo-acceptor assembles tetra-sialic acid efficiently, overcoming the low α-selectivity of α-anomer and purifying it remain to be achieved. Furthermore, mono- and di-sialic acids were, respectively, conjugated on carrier protein, keyhole limpet hemocyanin. The enzymatic hydrolysis method is recommended for estimating the amount of sialic acid on a protein conjugate.     

A general and efficient stereoselective synthesis of γ-azido-tetrahydrofuran carboxylic acids from glycals

An efficient, direct and general synthesis of enantiopure γ-azido-tetrahydrofuran carboxylic acid monomers (5-8) from commercially available glycals, suitable to design peptidomimetic oligomers with predisposed conformation, is described. The single crystal X-ray study of 8 showed that the compound crystallized in orthorhombic space group. The crystal-packing showed the presence of weak intermolecular C-H?O and aliphatic C-H?π interactions.     

Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane–water. The amino moiety must be protonated and located α to a carboxylic acid function in order to undergo initial diazotization and successive hydroxylation, since neither β-amino acids nor acid derivatives such as esters and amides undergo hydroxylations. The method is successfully applied for the synthesis of 18 proteinogenic amino acids.     

Direct synthesis of α-thio aromatic acids from aromatic amino acids

Modified amino acids are useful synthetic components in both chemistry and biology. Here we describe a simple, scalable two-step procedure to generate α-thio aromatic acids from aromatic amino acids with yields of up to 96%. Diazotization and α-lactone mediated bromination efficiently form the α-bromo acid with retention of configuration. Thiol substitution with mild reagents such as sodium hydrosulfide or sodium trithiocarbonate provides the inverted, free α-thio acid. The mildly acidic soft nucleophile can then be utilized in many synthetic applications.     

Recent progress on the stereoselective synthesis of cyclic quaternary α-amino acids

The most recent papers describing the stereoselective synthesis of cyclic quaternary α-amino acids are collected in this review. The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton.     

A new strategy for the stereoselective synthesis of unnatural α-amino acids

A new method for the synthesis of racemic non-proteinogenic α-amino acids has been developed, which involves (i) hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron rich alkenes such as enol ethers, enamines and allylsilanes, (ii) NaCNBH₃ reduction of the CN bond in the oxazines thus generated, the stereochemistry of the products being controlled by epimerisation of the thermodynamically less stable isomer to the more stable one, (iii) protection of the N-H group as N-Boc and (iv) finally, N-O bond cleavage of both free and protected products to give proline or bis-homoserine derivatives, respectively. An example with concomitant reduction of the carboxylate group, resulting in the formation of the respective amino alcohol is reported. Applying this methodology to a homochiral enol ether, the protected parent d-proline was prepared in enantiomerically pure form, whereas the asymmetric synthesis of the respective bis-homoserine was unsuccessful.     

Regio- and stereoselective synthesis of functionalized oxazolidin-2-ones from the reaction of α-epoxyketones with urea

A regio- and stereoselective synthesis of functionalized 4,5-disubstituted oxazolidin-2-ones is reported with moderate to good yields from the reaction of α-epoxyketones with urea in the presence of p-toluenesulfonic acid as the catalyst. Correspondence: Farzad Nikpour, Department of Chemistry, Faculty of Sciences, University of Kurdistan, P.O. Box 66315-416, Sanandaj, Iran.     

Regio- and stereoselective synthesis of functionalized oxazolidin-2-ones from the reaction of α-epoxyketones with urea

A regio- and stereoselective synthesis of functionalized 4,5-disubstituted oxazolidin-2-ones is reported with moderate to good yields from the reaction of α-epoxyketones with urea in the presence of p-toluenesulfonic acid as the catalyst.     

Electrochemical synthesis of 1,2-disilylethanes from α-silylacetic acids

The synthesis of 1,2-disilylethanes [R(1)R(2)R(3)Si(CH(2))(2)SiR(1)R(2)R(3)] is usually conducted by using noble metal reagents or catalysts. This work describes a new electrochemical synthetic method for their preparation in good yields by oxidation of α-silylacetic acids at Pt anodes (Kolbe electrolysis). Most of the reported synthesized 1,2-disilylethanes in this work are unknown.     

Efficient synthesis of (±)-γ-lycorane employing stereoselective conjugate addition to nitroolefin

(±)-γ-Lycorane 3 was synthesized in 52% overall yield via seven steps from 5 by employing the highly stereoselective nitro-Michael cyclization of 5 to 9 and diastereoselective conjugate addition of aryllithium to a nitroolefin 10 as two key steps.     

Efficient one-pot synthesis of α-aminophosphonates from aldehydes and ketones catalyzed by ytterbium(III) triflate

An efficient three component one-pot synthesis of N-silylated α-aminophosphonates and α,α-disubstituted α-aminophosphonates was developed using Yb(OTf)₃ as a catalyst at room temperature under mild conditions.     

A stereoselective synthesis of bis-β-amino acids

Enantiopure bis-β-amino acids (5a–c) were prepared from chiral bis-sulfinimines (3a–c) in >97% ee via stereoselective addition of the sodium enolate of methyl acetate followed by hydrolysis.     

A stereoselective synthesis of the allo-bile acids from the 5β-isomers

The allo-bile acids are a subset of the family of steroidal detergents found in most vertebrates. Because there are no major biological feedstocks for isolation of the allo-bile acids, they must be synthesized from the abundant 5β-reduced isomers. Here we report a general set of methods for the synthesis of allo-bile acids from the corresponding 5-β isomers demarcated by a selective C-3 oxidation, IBX unsaturation, and stereoselective saturation.     

Enzymatic α(1→2)-l-fucosylation: investigation of the specificity of the α(1→2)-l-galactosyltransferase from Helix pomatia

The α(1→2)-l-galactosyltransferase from Helix pomatia transfers an l-fucosyl residue from GDP-l-Fucose to a terminal, non-reducing d-galactopyranosyl moiety of an oligosaccharide. The extent of the enzyme's specificity towards the stereochemistry at the d-galactopyranosyl anomeric centre, the site of interglycosidic linkage and the nature of the subterminal oligosaccharide residue has been investigated using HPAEC-PAD and MALDI-TOF technology. This α(1→2)-l-galactosyltransferase is specific for d-galactopyranosyl β-linkages, independent of the site of the interglycosidic linkage and aglycone configuration and with limited specificity for the nature of the subterminal sugar residue.     

Novel approach to the synthesis of aliphatic and aromatic α-keto acids

A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.     

Efficient synthesis of functionalized 1,3-dihydroisobenzofurans from salicylaldehydes:Application to the synthesis of escitalopram

An efficient synthesis of substituted 1,3-dihydroisobenzofurans is developed. In this novel route, oaroylbenzaldehydes, as key intermediates, can be obtained by lead tetraacetate oxidation of Naroylhydrazones of salicylaldehydes. The mild and general strategy enables the synthesis of various substituted 1,3-dihydroisobenzofurans in high yields. Moreover, this method can be applied to efficiently synthesize escitalopram.     

A new stereoselective synthesis of sterically constrained uncommon α,α′-dialkylated α-amino acids. Part 2

The alkylation of the diastereomeric mixture of the chiral morpholinone derivatives 5 and 6 occurs with good yield and a prevalence of the cis isomer. Cleavage of the alkylated intermediates 7b,c yields enantiomerically pure sterically constrained uncommon α,α′-dialkylated α-amino acids. The absolute configuration of the new stereocentres has been assigned on the basis of the ¹H NMR spectra and NOE measurements. A model to explain the observed diastereoselection is proposed.     

Iron-catalyzed, highly regioselective synthesis of α-aryl carboxylic acids from styrene derivatives and CO2

The iron-catalyzed hydrocarboxylation of aryl alkenes has been developed using a highly active bench-stable iron(II) precatalyst to give α-aryl carboxylic acids in excellent yields and with near-perfect regioselectivity. Using just 1 mol % FeCl(2), bis(imino)pyridine 6 (1 mol %), CO(2) (atmospheric pressure), and a hydride source (EtMgBr, 1.2 equiv), a range of sterically and electronically differentiated aryl alkenes were transformed to the corresponding α-aryl carboxylic acids (up to 96% isolated yield). The catalyst was found to be equally active with a loading of 0.1 mol %. Preliminary mechanistic investigations show that an iron-catalyzed hydrometalation is followed by transmetalation and reaction with the electrophile (CO(2)).     

Efficient and stereoselective synthesis of threo-β-hydroxy-l-glutamic acid via a tandem (Z)-olefination-conjugate addition

threo-β-Hydroxy-l-glutamic acid 1 is an attractive target as a biologically active compound and as a chiral synthon. The required β-hydroxyl group in 1 was efficiently and stereoselectively introduced via an intramolecular conjugate addition of the N-hydroxymethyl group of γ-amino-α,β-unsaturated (Z)-ester 4. While the corresponding (E)-ester 3 gave a lower selectivity of ca. 5:1 in the intramolecular conjugate addition, a selectivity of up to 70:1 was shown with (Z)-ester 4. The tandem (Z)-olefination-conjugate addition could be achieved by simply changing the reaction conditions to give a selectivity of >20:1. Thus, the target compound 1 was obtained as its hydrochloride salt in 70% overall yield over four steps from lactol 2.