Synthesis of optically active α-sulfinylacetaldehyde

Optically active α-sulfinylacetaldehyde is prepared by formylation of the (R)-methyl p-tolylsulfoxide anion with N-formylpiperidine.     

Synthesis of optically active α-aminobenzolactam via an oxidative–cyclization reaction

A convergent pathway for the asymmetric synthesis of (−)-α-aminobenzolactam 1 is described. For the first time, the key intermediate N-methoxybenzolactam 8 was prepared from l-homophenylalanine ethyl ester hydrochloride (LHPE·HCl) 5 by employing an oxidative cyclization in the presence of trifluoroacetic acid (TFA).     

Preparation of chiral α-diazophosphonic acid derivatives

The chiral α-diazophosphonic acid derivatives 3, 6 and 8 were prepared from (−)-ephedrine and (S,S)-N,N′-dimethyl-1,2-diaminocyclohexane; preliminary experiments suggest that the chiral auxiliary exerts little influence in the dirhodium(II) acetate catalysed OH and NH insertion reactions.     

Synthesis of α,γ-peptide hybrids by selective conversion of glutamic acid units

The site-selective modification of small peptides at a glutamate residue allows the ready preparation of α,γ-hybrids. In this way, a single peptide can be transformed into a variety of hybrid derivatives. The process takes place under very mild conditions, and good global yields are obtained.     

Synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries

We report an efficient and reliable method for the synthesis of α-chiral-β,γ-unsaturated carboxylic acid derivatives using chiral auxiliaries and vinylacetic acid. Two well-established chiral auxiliaries ((S,S)-pseudoephedrine and (R)-benzyl-oxazolidinone) were chosen to test the merits of this method. Six different electrophiles were examined in the diastereoselective alkylation with both auxiliaries. The pseudoephedrine auxiliary provided isolated yields between 61 and 85% and diastereomeric ratios all greater than 96:4. Employing the same reactions as with the pseudoephedrine derivative, the corresponding oxazolidinone auxiliary provided isolated yields between 0 and 80% with diastereomeric ratios from 80:20 to 93:7.     

The reaction of optically active α-aminocarboxylic acid hydrazides with triethyl orthoesters

New derivatives of 2-(1-amino-1-phenylmethyl)-1,3,4-oxadiazole and 1,2,4-triazin-6-one were synthesised in the reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The electronic and steric effects of substituents at the α position influencing the formation of five- or six-membered products are discussed.     

Synthesis of unnatural N-glycosyl α-amino acids via Petasis reaction

A convenient and efficient protocol for the synthesis of unnatural N-glycosyl a-amino acids was developed.Condensation of 1,3,4,6-tetra-O-actyl-β-D-glucosamine hydrochloride,alkenyl boronic acid,and glyoxylic acid was achieved in CH_2C1_2 to give the derivatives of 2-(N-glycosyl)aminobut-3-enoic acid which may find applications in glycobiology research and medicinal chemistry.     

Synthesis of chiral pyrrolidine and pyrrole derivatives through the chemoselective Dieckmann reaction of α,β-aminodiesters

α,β-Aminodiesters were allowed to react with t-BuOK in THF at −78°C. The chemoselectivity of the Dieckmann cyclization was controlled by the nature of the substituents R₃ and R₄, allowing the preparation of pyrrolidine or pyrrole derivatives.     

Synthesis of cis,cis-diunsaturated α-meromycolic acid by a palladium-catalysed alkyl–alkyl Negishi reaction

The first total synthesis of cis,cis-diunsaturated α-meromycolic acid has been accomplished using a convergent strategy and a palladium-catalysed alkyl–alkyl Negishi reaction as the key step.     

Synthesis of optically active polymers bearing amino acid moieties by atom transfer radical polymerization

We report here an approach toward the synthesis of optically active polyacrylamide bearing amino acid moieties, poly[N- methacryloyl L-leucine methyl ester] (PMALM), with controlled average number molecular weight (Mn) and relatively narrow polydispersity index (PDI, Mw/Mn < 1.3) by atom transfer radical polymerization (ATRP) using initiating system methyl 2- bromopropionate/CuBr/tris(2-dimethylaminoethyl) amine. The optical properties of the resulting polymers were evaluated fromspecific optical rotation value and CD spectra.     

Synthesis of optically active medium-sized α-aminolactams via ring-closing metathesis

The synthesis of optically active medium-sized α-aminolactams via ring-closing metathesis is described. The amidation of optically active N-Boc-allylglycine derivatives with N-protected alkenylamine, and ring-closing metathesis resulted in the formation of medium-sized α-aminolactams with good yield.     

Synthesis of α-CF3-substituted γ,δ-didehydro lysine derivatives

An efficient and selective access to novel α-CF₃-substituted γ,δ-didehydro lysine derivatives and their phosphorus analogues has been developed via the Cu-catalyzed Mannich reaction of α-amino α-propargyl α-trifluoromethyl carboxylates or phosphonates with different secondary amines and paraformaldehyde.     

Synthesis of α,β-diamino acid derivatives via asymmetric Mannich reactions of glycine imino esters catalyzed by a chiral phosphoramidite·silver complex

AgOTf·phosphoramidite complexes efficiently catalyze the enantioselective Mannich-type reaction between benzophenone-imine glycine methyl ester and N-tosyl aldimines in the absence of a base. The corresponding syn-adducts, which are the direct precursors of α,β-diamino acids, are obtained with moderate to good syn-diastereoselectivities (up to 9:1) and high enantioselectivities (up to 99% ee).     

Synthesis of optically active α-hydroxy ketones by enantioselective oxidation of silyl enol ethers with a fructose-derived dioxirane

Optically active α-hydroxy ketones 3 have been prepared in moderate to high enantioselectivities by the asymmetric oxidation of the silyl enol ethers 2 with in situ generated dioxirane from the fructose-derived ketone 1. Best results (ee values up to 82%) for this novel non-transition metal mediated asymmetric α-hydroxylation may be obtained, when an excess of the fructose-derived ketone 1 is employed at pH ca. 8 and short reaction times. Valuable mechanistic information on the spiro versus planar transition states for the oxygen-transfer process has been aquired through the absolute configuration of the resulting α-hydroxy ketone 3 products.     

Synthesis of β-substituted tetrahydrofurans by the prins reaction

Mixtures of 3-trif uoroacetoxy- and 3-chloro-4-alkyltetraliydrofurans were synthesized by the reaction of a series of-olefins with formaldehyde in trifuoroacetic acid and trimethylchlorosilane.The characteristics of the mixtures of cis and trans isomers are given, and the n_D ²⁰ values are given for the trans isomers.Bashkir State University, Institute of Fine Organic Synthesis. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 605–608, May, 1995. Original article submitted November 4, 1994; revision submitted May 10, 1995.     

Efficient synthesis of optically active α-substituted glutamate analogs possessing α-hydroxymethyl and α-alkoxymethyl groups

Highly enantioselective synthesis of (2R)-α-(hydroxymethyl)glutamate (1), a selective agonist of mGluR2 and 3, was achieved in short steps using an asymmetric version of the Strecker synthesis. This was converted into its α-methoxymethyl- and α-benzyloxymethyl derivatives 2 and 3, possible ligands as tools to investigate glutamate receptors, via protection of the sterically hindered amino group by means of phase transfer catalyst.     

Synthesis of a chiral phosphonium salt for the preparation of α-substituted alaninol derivatives

We herein report the synthesis of a chiral phosphonium salt, {[(4S)-4-methyl-2-oxo-1,3-oxazolidin-4-yl]methyl}(triphenyl)phosphonium iodide 13 to provide a new Wittig reagent for the general method of synthesizing α-substituted alaninol derivatives. Our method described here is widely applicable to reactions with various types of aldehyde to afford olefin products with high E-selectivity, enabling us to provide a new approach to the synthesis of chiral S1P₁ agonists including our key intermediates, and of the trace amine-associated receptor 1 (TAAR1) agonist.     

Synthesis of optically active α-bromohydrins via reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase

Enantiomerically pure (S)-α-bromohydrins were prepared by the reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase from Candida magnolia with high yield and excellent enantiomeric excess when methyl tert-butyl ether was employed as the co-solvent, while avoiding the formation of by-products. This provides a new approach to access these chiral α-bromohydrins which are of pharmaceutical importance.