170111-23-6

Basic information

• Product Name: N-(4-Morpholinylcarbonyl)-L-phenylalanine 1(S)-(2-phenylethyl)-3-(phenylsulfonyl)-2(E)-propenyl amide
• Synonyms: APC-2848; K02
• CAS NO: 170111-23-6
• Molecular Formula: C₃₁H₃₅N₃O₅S
• Molecular Weight: 561.7057
• Mol File: 170111-23-6.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: N-(4-Morpholinylcarbonyl)-L-phenylalanine 1(S)-(2-phenylethyl)-3-(phenylsulfonyl)-2(E)-propenyl amide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-Morpholinylcarbonyl)-L-phenylalanine 1(S)-(2-phenylethyl)-3-(phenylsulfonyl)-2(E)-propenyl amide(170111-23-6)
• EPA Substance Registry System: N-(4-Morpholinylcarbonyl)-L-phenylalanine 1(S)-(2-phenylethyl)-3-(phenylsulfonyl)-2(E)-propenyl amide(170111-23-6)

Safety Data

• Hazardous Substances Data: 170111-23-6(Hazardous Substances Data)

Upstream product

• 114473-20-0 (S)-methyl 2-(morpholine-4-carboxamido)-3-phenylpropanoate 
• 15159-40-7 4-morpholinocarbonyl chloride 
• 114457-62-4 Nα-(4-morpholinecarbonyl)-L-phenylalanine 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 216656-61-0 C₂HF₃O₂*C₁₇H₁₉NO₂S 
• 170112-07-9 (S)-tert-butyl (1-oxo-4-phenylbutan-2-yl)carbamate 
• 82732-07-8 Boc-L-homophenylalanine 
• 170111-73-6 (3S)-N-(1-benzenesulfonyl-5-phenyl-pent-1-en-3-yl)carbamic acid tert-butyl ester 
• 1161-13-3 N-Cbz-L-Phe 
• 18328-11-5 3-benzyl propionaldehyde 
• 56069-39-7 diethyl phenylsulfonylmethylphosphonate 
• 110-91-8 morpholine 
• 530-62-1 1,1'-carbonyldiimidazole 
• 119624-66-7 benzyl (2S)-2-isocyanato-3-phenylpropanoate 

Downstream Products

• 1428441-82-0 phenyl (E)-3-((N-morpholine-4-carbonyl)phenylalanyl)amino-5-phenylpent-2-enyl sulfone 
• 1428441-89-7 (2S)-N-(5-phenylpent-1-en-3-ylidene)-2-(N-morpholine-4-carbonyl)amino-3-phenylpropanamide 
• 1428441-83-1 phenyl (Z)-3-((N-morpholine-4-carbonyl)phenylalanyl)amino-5-phenylpent-2-enyl sulfone 

Relevant articles and documents

Asymmetric Synthesis of γ-Amino-Functionalised Vinyl Sulfones: De Novo Preparation of Cysteine Protease Inhibitors

The enantioselective azo-based -amination of an aldehyde followed by a Horner Wadsworth Emmons-based vinyl sulfone formation is reported. The thus obtained optically active N,N'-diprotected trans-(phenylsulfonyl)vinyl hydrazine products were then converted into the corresponding N-functionalised trans-(phenylsulfonyl)vinyl amines. Specifically, reaction of 4-phenylbutanal with di-tert-butyl azodicarboxylate (DBAD) in the presence of L- or D-proline, followed by addition of diethyl [(phenylsulfonyl)methyl]phosphonate, gave either enantiomer of di-tert-butyl trans-1-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]hydrazine-1,2-dicarboxylate. The enantiomeric excesses of the (+)- and (-)-enantiomers prepared in this manner were in the range 86 89%. The conversion of these -hydrazino vinyl sulfones into the corresponding -amino-substituted compounds was achieved following a Boc deprotection, Zn reduction, N-functionalisation sequence. This three-step sequence was reasonably efficient (approx. 50%) and no erosion of enantiopurity was found to have taken place. The compounds accessed via this process include both enantiomers of tert-butyl trans-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]carbamate and epimeric dipeptide mimetics including 4-methyl-N-{(S)-1-oxo-3-phenyl-1-[((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino]propan-2-yl}piperazine-1-carboxamide (also known as K777).

Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors

This research investigates the synthesis and inhibitory potency of a series of novel dipeptidyl allyl sulfones as clan CA cysteine protease inhibitors. The structure of the inhibitors consists of a R1-Phe-R2-AS-Ph scaffold (AS=allyl sulfone). R1 was varied with benzyloxycarbonyl, morpholinocarbonyl, or N-methylpiperazinocarbonyl substituents. R2 was varied with either Phe of Hfe residues. Synthesis involved preparation of vinyl sulfone analogues followed by isomerization to allyl sulfones using n-butyl lithium and t-butyl hydroperoxide. Sterics, temperature and base strength were all factors that affected the formation and stereochemistry of the allyl sulfone moiety. The inhibitors were assayed with three clan CA cysteine proteases (cruzain, cathepsin B and calpain I) as well as one serine protease (trypsin). The most potent inhibitor, (E)-Mu-Phe-Hfe-AS-Ph, displayed at least 10-fold selectivity for cruzain over clan CA cysteine proteases cathepsin B and calpain I with a kobs/[I] of 6080±1390M-1s-1.

Vinyl Sulfones as Mechanism-Based Cysteine Protease Inhibitors

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