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Amino-acid derived 2-nitrobenzenesulfonamides were successfully condensed under Mitsunobu conditions with 2,3,4,6-tetra-O-acetyl- d -glucose to afford the fully protected glucosylamines in excellent yield. Upon total deprotection, these compounds rearranged to provide the corresponding Amadori products in good overall yield.

1-[( S )-1-(2-Nitrobenzenesulfonyl)-aziridin-2-yl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane 5 was ring opened regioselectively with a variety of lithium acetylides to give α-amino acids bearing γ,δ-unsaturation in very good to excellent yields. The 2-nitrobenzenesulfonyl and OBO ester protecting groups were removed in excellent overall yield.

Serine derived aziridine 15 was successfully ring-opened with amino acid esters to give diaminopropionic acid derivatives in excellent yield and regioselectivity. These compounds were cyclised to form the corresponding β-lactams in good overall yield. One example was fully deprotected to give target compound 1 (n = 1, R = Me) in excellent yield.

Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper, we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the ‘reduced’ amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards γ-glutamyl-transpeptidase (γGT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the γ-glutamyl-cysteine amide bond greatly improved stability towards γGT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors.

A versatile route of synthesis of phosphorus oxide and phosphorus borane templates starting from the bifunctional phosphorylating agent bis(diisopropylamino)ethynylphosphine is presented. Ring-closing enyne metathesis using 4,5-dihydro-imidazol-2-ylidene ruthenium benzylidene complex 3 on these types of substrates led to the formation of mono- and bicyclic phosphorus heterocycles.

Glutathione (GSH) conjugates inhibit enzymes that are involved in drug metabolism and drug resistance, but their cellular uptake is very low. To improve membrane-permeability, we synthesized a novel GSH-conjugate analogue with a tetrazole carboxylate isostere at the glycine position. Introduction of the tetrazole decreases inhibitory potency towards CDNB conjugation by glutathione S-transferase. However, the tetrazole derivative inhibited 2-bromoisovalerylurea conjugation in rat liver cytosol, as well as in hepatocytes.

In order to develop a generic treatment of sepsis caused by infections with Gram-negative bacteria, a series of pseudo-disaccharide analogues of lipid A (1–5) was synthesized. These adducts not only harbor a 2-acylaminodideoxynojirimycin unit mimicking the transition state of the glycosidic hydrolysis, but also a 2-N, 3-O-diacylated glucosamine moiety capable of generating catalytic antibodies with more selective glycosidase properties towards lipid A.

In the recent past sugar-derived cyclopropylamines were proposed as structurally new glycosidase inhibitors. In this Letter we report our efforts in the synthesis of a set of α-glucose configured oxabicyclo[4.1.0] heptanes, based on this hypothesis, bearing an amine substituent on the propyl ring and reveal that their inhibitory potential towards a range of mammalian glucosidases is modest.

The synthesis of ionic support 1 and its application in the preparation of a set of amides and sulfonamides is described. The potential of 1 is further exemplified by its use in a one-pot multistep ionic liquid phase assisted synthesis of tirofiban analogue 2.

The highly functionalized piperidine 5a was synthesized in only 4 steps starting from ribose using a tandem retro‐Michael‐[2 + 3]‐cycloaddition process as the key transformation. The versatility of the tandem retro‐Michael‐[2 + 3]‐cycloaddition was demonstrated by the synthesis of novel piperidines 5b, 5c, 11 and 16.

Diphenylsulfoxide in combination with triflic anhydride provides a very potent thiophilic glycosylation promotor system, capable of activating disarmed thioglycosides. The usefulness of this novel thiophilic activator is illustrated in a successful chemoselective glycosylation sequence in which the donor thioglycoside in the first condensation step may be either armed or disarmed. [reaction: see text]

Four partially protected stereoisomeric cyclopentenetriols 5, 10, 15 and 21 have been prepared by ring-closing metathesis of carbohydrate-derived 1,6-dienes. The presence of a differentiated allylic alcohol in the cyclopentenetriols allows a variety of synthetic transformations, underlining the synthetic use of the prepared cyclopentenetriol derivatives as chiral building blocks.

A ring-closing metathesis (RCM) and a ring-opening metathesis (ROM) are combined in a domino process giving access to a variety of aza- and oxacyles, equipped with highly functionalized side chains, starting from readily accessible cyclopentenyl or cycloheptenyl ethers and amines. The role of different protective groups is examined as well as the influence of the relative configuration of stereocenters of the substrate molecules. Substituted 2,5-dihydro-furans and -pyrroles, 1,2,5,6-tetrahydropyranes and -pyridines as well as 2,3,4,7-tetrahydrooxepines are available via this methodology.

A convenient route for the synthesis of phosphorus diolefinic templates starting from the bifunctional reagent bis(diisopropylamino)vinylphosphine is presented. Ring closing olefin metathesis on this type of diene substrate revealed that the newly developed 4,5-dihydro-imidazol-2-ylidene ruthenium benzylidene complex 4 is in all aspects superior to the previously developed Grubbs’ catalyst 1. © 2000 Elsevier Science Ltd. All rights reserved.