Imre Schlemminger

2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase.

Hydroxylation of hypoxia-inducible factor, a nuclear transcription factor, is catalysed by iron and 2-oxoglutarate dependent hydroxylases. Various analogues of the 2-oxoglutarate cosubstrate were synthesised and shown to inhibit the activity of human hypoxia-inducible factor-1alpha prolyl hydroxylases in cell-free extracts.

Analogues of dealanylalahopcin are inhibitors of human HIF prolyl hydroxylases

Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases.

Multicomponent synthesis of novel amino acid-nucleobase chimeras : A versatile approach to PNA-monomers

This paper describes a multicomponent approach to novel totally protected precursors of PNA-monomers via Ugi 4CC. The obtained bisamides are converted into several partially protected PNA-monomers or derivatives thereof using three different procedures. Methods for hydrolysis are shown to be dependent on the nature of the isocyano component required for Ugi 4CC. Several novel monomers suitable for oligomer synthesis are prepared demonstrating the high versatility of the reaction sequence.

Modified PNAs: a simple method for the synthesis of monomeric building blocks.

The synthesis of PNA-monomers with variations in the substitution pattern using the Ugi-Reaction is described. The one-pot procedure leads to new totally protected PNA-monomers which can be selectively cleaved to N-protected monomeric building blocks for PNA synthesis.

Synthesis of the first enantiomerically pure 3-thiazolines via Asinger reaction

Abstract The first synthesis of an enantiomerically and diastereomerically pure 3-thiazoline via modified Asinger reaction using a galactose derived chiral auxiliary is described. The absolute configuration of this heterocyclic imine has been elucidated via X-ray analysis. In addition, the 3-thiazoline has been successfully derivatized under Ugi conditions.

The Synthesis of Novel Cyclic β-Amino Acids as Intermediates for the Preparation of Bicyclic β-Lactams

Several derivatives of homopipecolic acid are prepared by α-amino alkylation of malonic acid with cyclic imines 6 and 7. These are prepared on a large scale and with different substitution patterns. The β-amino acids 8 and 9 were formed in high yield and with remarkable diastereoselectivity if chiral imines are used as starting materials. The diastereoselectivity of the amino alkylation leading to homopipecolic acid analogues is compared to those of thiazolidineacetic acids by epimerisation experiments. A method for resolution of the obtained racemic β-amino acids by diastereomeric salt formation is described. The β-amino acids 9 and 15 were converted into their corresponding carbacepham analogues 14 and isopenam 16. The isopenam endo-16 was selectively epimerised by mild basic treatment of the N/S-acetal to give an exo-configured precursor of isopenicillin G.

Highly diastereoselective hydrophosphonylation of cyclic imines using BINOL as source of chirality

The first highly diastereoselective (dr up to >95:5) hydrophosphonylation of heterocyclic imines by a chiral phosphorus nucleophile is introduced. Addition of binaphthol ester of phosphorus acid towards BF3-activated 3-thiazolines gives the corresponding (aR*,4R*)-4-thiazolidinylphosphonates almost exclusively as elucidated by X-ray analysis. # 2000 Elsevier Science Ltd. All rights reserved.

Diastereoselective Lewis acid mediated hydrophosphonylation of heterocyclic imines: a stereoselective approach towards α-amino phosphonates

The synthesis of new chiral α-amino phosphonates by the Lewis acid mediated addition of bisesters of phosphonic acid to 3-thiazolines (2,5-dihydro-1,3-thiazoles), is described. The diastereoselectivity of the reaction using chiral reactants was systematically investigated. The chiral BINOL-phosphonate 1 was found to be a highly stereoselective phosphonylating agent towards 3-thiazolines. Structural aspects of the resulting thiazolidinylphosphonates were studied by NMR and X-ray analyses. The role of the Lewis acid as a spatial mediator is discussed and a quantum chemical description of the Lewis acid mediated hydrophosphonylation presented.

Multicomponent synthesis of tripeptides containing pipecolic acid derivatives: selective induction of cis- and trans-imide bonds into peptide backbones

A simple approach to several tripeptides consisting of two terminal glycine fragments and a central pipecolic acid derivative was found via a multicomponent reaction starting from tetrahydropyridines. The protected peptides 2a–g were formed in high yields and with different substitution patterns of the central heterocyclic amino acid. In cases where chiral imines were used the target compounds were obtained with remarkable diastereoselectivity. The influence of different substituents attached to the pipecolic acid fragment on N-terminal amide isomerism was investigated using X-ray crystallography and NMR spectroscopic methods.

Synthesis of novel pipecolic acid derivatives: a multicomponent approach from 3,4,5,6-tetrahydropyridines

A simple approach to several derivatives of pipecolic acid is via a multicomponent reaction starting from cyclic imines 2, which are synthesized on a large scale and with different substitution patterns. The protected amino acids 3 are formed in high yields. In cases where chiral imines are used the target compounds are obtained with remarkable diastereoselectivity. Bisamides 3 serve as versatile precursors for the preparation of a wide range of amino acid derivatives. Different methods of hydrolysis of 3 lead to the free pipecolic acids or its derivatives. Employment of methanol or ethanethiol as a nucleophile in the acid-mediated conversion of enamides 3 results in N-acylated amino acid esters 5. Furthermore a method for the resolution of the obtained racemic α-amino acids via diastereomeric salt formation is described.