898558-08-2

Upstream product

• 24629-25-2 (S)-isoleucinol 
• 98-59-9 p-toluenesulfonyl chloride 
• 34235-81-9 3-methyl-2-{[(4-methylphenyl)sulfonyl]amino}pentanoic acid 
• 73-32-5 L-isoleucine 

Downstream Products

• 903516-19-8 (S)-O-(tert-butyldimethylsilyl)-N-(p-toluenesulfonyl)-isoleucinol 
• 1200695-81-3 (2S)-3-methyl-2-(4-methylphenylsulfonamido)pentyl methanesulfonate 
• 1032477-31-8 5,5'-di-tert-butyl-3,3'-bis[(2S,4S)-3-(4-methylbenzenesulfonyl)-4-((1S)-1-methylpropyl)-1,3-oxazolidinyl]biphenyl-2,2'-diol 
• 903516-24-5 (S,S)-4-aza-5-sec-butyl-6-(tert-butyldimethylsilanyloxy)-4-(p-toluenesulfonyl)hexanal dimethyl acetal 
• 903516-34-7 tert-butyl (E)-(7S)-6-aza-7-((S)-sec-butyl)-8-hydroxy-6-(p-toluenesulfonyl)oct-2-enoate 
• 903516-43-8 tert-butyl (E)-(7S)-6-aza-8-bromo-7-((S)-sec-butyl)-6-(p-toluenesulfonyl)oct-2-enoate 
• 903516-28-9 (5S)-4-aza-5-((S)-sec-butyl)-1-hydroxy-7-oxa-4-(p-toluenesulfonyl)cycloheptane 

Relevant academic research and scientific papers

Synthesis and hetero-Diels-Alder reactions of enantiomerically pure dihydro-1: H -azepines

Thermolysis of enantiomerically pure 3-substituted 7,7-dihalo-2-azabicyclo[4.1.0]heptanes in the presence of K2CO3 gives in good yields 2-alkyl-6-halo-1-tosyl-2,3-dihydro-1H-azepines. These undergo highly stereoselective [4+2] cycloaddition reactions with heterodienophiles and arylation/alkenylation under Suzuki conditions.

Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step

Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids. The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.

Asymmetric Strecker reaction of N-benzhydrylimines utilising new tropos biphenyldiol-based ligands

The synthesis of a library of N-arenesulfonyl-1,3-oxazolidinyl-substituted biphenyldiols is presented. A set of two central intermediates together with easily accessible N-arenesulfonylamino alcohols furnish a broad variety of 1,3-oxazolidines. These are applied as chiral tropos ligands in a titanium-mediated Strecker-type reaction of N-benzhydrylimines. A correlation between the ee values in the product and the diastereomeric ratio concerning the chiral axis of the ligand is made. Those substituents in the ligand which proved to lead to a higher preference for one diastereomeric conformer of the chiral axis in related compounds now provide the most selective ligands. Two privileged ligands are identified that afford superior results in 8 of 13 screenings. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Discovery of a novel series of Notch-sparing γ-secretase inhibitors

Using a cell-based assay, we have identified a new series of Notch-sparing γ-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved γ-secretase inhibitory potency and Notch-sparing selectivity.

Synthesis of 2,4-disubstituted piperidines via radical cyclization: Unexpected enhancement in diastereoselectivity with tris(trimethylsilyl)silane

A novel approach to 2,4-disubstituted piperidines is reported, involving the radical cyclization of 7-substituted-6-aza-8-bromooct-2-enoates. Cyclization with tributyltin hydride affords the trans piperidines with trans/cis diastereomeric ratios ranging typically from 3:1 to 6:1. Cyclization with tris(trimethylsilyl)silane affords the same products with diastereomeric ratios of up to 99:1 in certain cases. The enhancement in diastereoselectivity results from the selective rearrangement of the minor stereoisomer through a cascade process involving radical cyclization to the piperidine radical, 1,5-radical translocation, and attack of the translocated radical onto the sulfonamide with extrusion of SO2 in a Smiles-type rearrangement. Slower trapping of the piperidine radical by tris(trimethylsilyl)silane compared to tributyltin hydride accounts for the occurrence of the rearrangement cascade in the former case.