849935-80-4

Upstream product

• 71336-69-1 (+/-)-trans-ethyl 1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylate 
• 849935-78-0 ethyl (3R,4S)-4-(acetyloxy)-1-benzylpyrrolidine-3-carboxylate 

Downstream Products

• 849935-87-1 (3S,4S)-N-tert-butoxycarbonyl-3-hydroxy-4-hydroxymethylpyrrolidine 

Relevant academic research and scientific papers

Tight binding enantiomers of pre-clinical drug candidates

MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors.

DEAZAPURINE ANALOGS OF 1'-AZA-L-NUCLEOSIDES

The invention relates to compounds of the formula (I), which are L-enantiomeric forms of nucleoside analogues, and to pharmaceutical compositions containing the compounds, methods of treating certain diseases, including cancer, bacterial infection, parasitic infection, and T-cell mediated diseases, using the compounds, processes for preparing the compounds, and intermediates useful in the preparation of the compounds.

Syntheses and bio-activities of the l-enantiomers of two potent transition state analogue inhibitors of purine nucleoside phosphorylases

(1R)-1-(9-Deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-l-ribitol [(+)-5] and (3S,4S)-1-[(9-deazahypoxanthin-9-yl)methyl]-4-(hydroxymethyl)pyrrolidin-3-ol [(-)-6] are the l-enantiomers of immucillin-H (d-ImmH) and DADMe-immucillin-H (d-DADMe-ImmH), respectively, these d-isomers being high affinity transition state analogue inhibitors of purine nucleoside phosphorylases (PNPases) developed as potential pharmaceuticals against diseases involving irregular activation of T-cells. The C-nucleoside hydrochloride d-ImmH [(-)-5)·HCl], now "Fodosine" is in phase II clinical trials as an anti-T-cell leukaemia agent, while d-DADMe-ImmH is a second generation inhibitor with extreme binding to the target enzyme and has entered the clinic for phase I testing as an anti-psoriasis drug. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the l-nucleoside analogues (+)-5·HCl and (-)-6, respectively, of d-ImmH and d-DADMe-ImmH, were prepared and their PNPase binding properties were studied. For the synthesis of compound (-)-6 suitable enzyme-based routes to the enantiomerically pure starting material (3S,4S)-4-(hydroxymethyl)pyrrolidin-3-ol [(-)-16] and its enantiomer were developed. The l-enantiomers (+)-5·HCl and (-)-6 bind to the PNPases approximately 5- to 600-times less well than do the d-compounds, but nevertheless remain powerful inhibitors with nanomolar dissociation constants. The Royal Society of Chemistry 2006.

METHOD FOR PREPARING 3-HYDROXY-4-HYDROXYMETHYL-PYRROLIDINE COMPOUNDS

This invention relates to a method of preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, a key intermediate compound for the synthesis of certain inhibitor compounds, including the step of enzyme catalysed enantioselective esterification of an hydroxy group of an hydroxypyrrolidine. The invention further relates to a method for preparing (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, which is the enantiomer of (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine.