630108-94-0

Upstream product

• 130981-51-0 (2S,2'S)-4,4'-disulfanediylbis(2-(tert-butoxycarbonyl)amino)butanoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 601491-40-1 N,N′-di(tert-butoxycarbonyl)-L-homocystine di(tert-butyl)ester 

Downstream Products

• 1338787-22-6 S-(N-benzyl-4,5-dideoxy-2,3-O-isopropylidene-D-ribono-1,4-lactam-5-yl)-N-(tert-butoxycarbonyl)-1-homocysteine tert-butyl ester 
• 1245941-92-7 tert-butyl N-(tert-butoxycarbonyl)-S-(3-tosyloxypropyl)-homocysteinate 
• 1101107-61-2 2(S)-tert-butoxycarbonylamino-4-[(2S,3R,4S)-3-hydroxy-2,4,5-tris(p-methoxybenzyloxy)-pentylsulfanyl]-butyric acid tert-butyl ester 
• 888949-71-1 tert-butyl (2S)-4-[(2S,3R)-2,3-bis(benzyloxy)-3-tert-butoxycarbamoylpropylmercapto]-2-tert-butoxycarbonylaminobutyrate 
• 630108-98-4 2S-tert-butoxycarbonylamino-4-[(2S,3R)-2,3,5-tris(p-methoxybenzoyloxy)-4-oxo-pentane-1-mercaptan]-butyric acid tert-butyl ester 
• 210354-30-6 4-(2-benzyloxycarbonylamino-ethylsulfanyl)-2-tert-butoxycarbonylamino-butyric acid tert-butyl ester 

Relevant academic research and scientific papers

S-Ribosylhomocysteine analogs containing a [4-thio]ribose ring

Abstract The [4-thio]-S-ribosylhomocysteine (SRH) analogs containing substitution of a sulfur atom for the endocyclic oxygen were synthesized by coupling of the 4-thioribose substrates with a thiolate generated from the protected homocysteine. Coupling of the protected 1-deoxy-5-O-mesyl-S-oxo-4-thio-D-ribofuranose with homocysteinate salt gave the C4 epimers of [4-thio]-SRH at the sulfoxide oxidation level lacking a hydroxyl group at anomeric carbon. Treatment of these sulfoxides with BF3·Et2O/NaI affected simultaneous reduction to sulfide and global deprotection affording 1-deoxy-4-thio-SRH analog. Treatment of the protected 1-deoxy-S-oxo-4-thio-D-ribofuranose sulfoxide with DAST/SbCl3 resulted in the fluoro-Pummerer rearrangement to give 4-thio-β-D-ribofuranosyl fluoride. Mesylation of the latter at 5-hydroxyl position followed by coupling with homocysteinate salt and subsequent global deprotection with trifluoroacetic acid afforded [4-thio]-SRH thiohemiacetal.

Synthesis and stability of S-(2-[18F]fluoroethyl)-L-homocysteine for potential tumour imaging

The F-18 labelled methionine derivative S-(2-[18F]fluoroethyl)- L-homocysteine ([18F]FEHCys) was prepared by a one-pot two-step synthesis via the protected S-(2-bromoethyl)-L-homocysteine 1 and S-(2-chloroethyl)-L-homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro-analogue (22% at 100°C in 30 min). However, [18F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. Copyright

Synthesis of isomeric analogues of S-ribosylhomocysteine analogues with homocysteine unit attached to C2 of ribose

LuxS (S-ribosylhomocysteinase; EC 4.4.1.21) is an enzyme that catalyzes the cleavage of the thioether linkage in the catalytic pathway of S-ribosylhomocysteine (SRH) which produces homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD). DPD is the precursor of the signaling molecules known as autoinducer 2 (AI-2) responsible for the bacterial quorum sensing (QS) identified as cell to cell communication. Inhibitors of LuxS should be able to interfere with its catalytic pathway thus preventing the formation of the autoinducer molecules. In this work, the synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by the coupling of the corresponding 2-bromo-2-deoxypentafuranosyl sugars with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate group from C5 was observed leading to a novel isomeric analogue of SRH in which Hcy moiety is attached to a ribose ring via C2-sulfur bond.

S-Ribosylhomocysteine analogues modified at the ribosyl C-4 position

4-C-Alkyl/aryl-S-ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplis

Revisiting synthetic preparation of the quorum sensing substrate S-d-ribosyl-l-homocysteine (SRH)

Cleavage of the thioether bond of S-d-ribosyl-l-homocysteine (SRH) by the enzyme S-ribosylhomocysteinase (LuxS) serves as the final biosynthetic step in the generation of the quorum sensing autoinducer AI-2 by bacteria. Herein, a revised chemical synthesis of SRH is presented at convenient scale and purity for in vitro studies of LuxS. Potassium bis(trimethylsilyl)amide (KHMDS) is identified as a judicious base for the formation of the thioether of the target compound from readily-accessible precursors: a thiol nucleophile derived from l-homocystine and a sulfonate-activated d-ribosyl electrophile. The exclusive use of acid-labile protecting groups allows for facile deprotection to the final product, producing the TFA salt of SRH in five synthetic steps and 26% overall yield. The chemically-synthesized material is isolated at high purity and demonstrated to serve as the LuxS substrate by an in vitro assay.

Radiosynthesis and biological evaluation of L- and D-S-(3-[ 18F]fluoropropyl)homocysteine for tumor imaging using positron emission tomography

Interest in radiolabeled amino acids for metabolic imaging of cancer and limitations with [11C]methionine has prompted the development of a new 18F-labeled methionine derivative S-(3-[18F] fluoropropyl)homocysteine ([

Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose ring

LuxS (S-ribosylhomocysteinase) catalyzes the cleavage of the thioether linkage of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a small signaling molecule that mediates interspecies bacteria

Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position

S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether bond of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which is the precursor of type 2 autoinducer for bacterial cell-cell communication. In this work, we have synthesized several SRH analogues modified at the ribose C3 position as potential inhibitors of LuxS. While removal or methylation of the C3-OH resulted in simple competitive inhibitors of moderate potency, inversion of the C3 stereochemistry or substitution of fluorine for C3-OH resulted in slow-binding inhibitors of improved potency. The most potent inhibitor showed a KI* value of 0.43 μM.

Catalytic Mechanism of S-Ribosylhomocysteinase (LuxS): Direct Observation of Ketone Intermediates by 13C NMR Spectroscopy

S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage of S-ribosylhomocysteine (SRH) to produce l-homocysteine and 4,5-dihydroxy-2,3-pentanedione (DHPD). This is a key step in the biosynthetic pathway of the type II autoinducer (AI-2) in both Gram-positive and Gram-negative bacteria. Previous studies demonstrated that LuxS contains a catalytically essential Fe2+ ion. The catalytic mechanism of LuxS was investigated using 2- and 3-13C-labeled SRH as substrate and 13C NMR spectroscopy. These studies revealed the presence of 2- and 3-keto intermediates in the catalytic pathway. The 2-keto intermediate was chemically synthesized, and its chemical and kinetic competence was demonstrated. The results support a catalytic mechanism in which the metal ion catalyzes an internal redox reaction, shifting the carbonyl group from the C-1 position to the C-3 position. Subsequent β-elimination at the C-4 and C-5 positions releases homocysteine as a free thiol. The results also suggest that Cys-84 and Glu-57 are the possible general acids/bases for proton transfer during catalysis and that the keto intermediates are released from the enzyme active site before rebinding and completion of the reaction. Copyright

Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine

The synthesis and in vitro evaluation of the acetamidine derivatives of hetero-substituted lysine and homolysine analogues have identified potent inhibitors of human nitric oxide synthase enzymes, including examples with marked selectivity for the inducible isoform. (C) 2000 Elsevier Science Ltd. All rights reserved.