189082-97-1

Upstream product

• 5447-02-9 3,4-dibenzyloxybenzaldehyde 
• 100-39-0 benzyl bromide 
• 121-33-5 vanillin 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 100-44-7 benzyl chloride 

Downstream Products

• 27688-87-5 (S)-3-(3,4-dibenzyloxyphenoxy)-1,2-epoxypropane 
• 177704-09-5 (2S)-(+)-1-(3',4'-dibenzyloxyphenoxy)-2,3-epoxypropane 
• 782436-39-9 (2S)-(-)-1-(3',4'-dibenzyloxyphenoxy)-3-(2-(3'',4''-dimethoxyphenyl)ethylamino)-2-propanol 
• 1196985-64-4 2,3-dibenzyloxy-7-trihydroxy-9-methoxy-6H-benzo[c]-chromen-6-one 
• 1402158-32-0 4,5-bis(benzyloxy)-2-bromophenol 
• 136944-33-7 4-(decyloxy)benzene-1,2-diol 
• 1256550-34-1 5-(n-decyloxy)-2-fluorophenol 
• 1256550-33-0 3-(n-decyloxy)-6,6-difluorocyclohexa-2,4-dienone 
• 1256550-32-9 C₁₆H₂₄O₃ 
• 247577-70-4 Acetic acid (R)-[4,5-bis-benzyloxy-2-(tert-butyl-dimethyl-silanyloxy)-phenyl]-((1S,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydro-naphthalen-1-yl)-methyl ester 
• 851279-15-7 3,4-di-benzyloxy-6-(7'-drimen-11'-ylidene)-2,4-cyclohexadienone 
• 189082-99-3 3,4-di-O-benzyl-2-bromo-1-O-tert-butyldimethylsilylbenzenetriol 
• 120951-85-1 1,2-di-O-benzyl-4-O-tert-butyldimethylsilylbenzenetriol 

Relevant academic research and scientific papers

P62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis

Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons.

Hybridization of β-Adrenergic Agonists and Antagonists Confers G Protein Bias

Starting from the β-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no β-arrestin-2 recruitment at both β1- and β2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and β-arrestin recruitment of the hybrid (S)-22, the full agonist epinephrine, and the β2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.

Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors

A concise 7-step total synthesis of (±)-fumimycin in 11.6% overall yield is reported. An acid-catalyzed intramolecular aza-Friedel–Crafts cyclization was developed to construct the benzofuranone skeleton of the natural product bearing an α,α-disubstituted amino acid moiety in a single step. Regioselective chlorination followed by a Suzuki–Miyaura cross-coupling rapidly enabled the preparation of a library of analogues which were evaluated against peptide deformylase for antibacterial activity.

Revision of the structure and total synthesis of altenuisol

A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds - a structure originally proposed as the structure of altertenuol - matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23% yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided. Total synthesis of altenuisol, a minor toxin in ubiquitous Alternaria spp. revealed that the originally proposed structure was not correct. Altenuisol was proved to have an isomeric structure by total synthesis. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleophilic deoxyfluorination of catechols

Nucleophilic deoxyfluorinaiton of one of the two hydroxyl groups of catechols has been developed via the Umpolung concept. This method was successively applied to naturally occurring catechols, such as catechins and dopamine, to produce novel fluorinated

Synthesis and β-adrenoceptor agonist properties of (±)-1-(3',4'- dihydroxyphenoxy)-3-(3',4'-dimethoxyphenyl) ethylamino-2-propanol hydrochloride, (±)-RO363.HCl, and the (2S)-(-)-isomer

The synthesis of (±)-1-(3',4'-dihydroxyphenoxy)-3-(3',4'- dimethoxyphenyl)ethylamino-2-propanol hydrochloride, (±)RO363.HCl, and the (2S)-(-)-isomer is described for the first time. The binding affinities for (±)-RO363.HCl, (2S)-(-)-RO363.HCl and a number of well known β-adrenoceptor agonists for transfected humanβ1,-, β2- and β3-adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (β1) and trachea (β2). The results indicate that both (±)-RO363 and (2S)-(-)-RO363 are selective for the human and rat β1-adrenoceptors. The (2S)-(-)-isomer of RO363, as expected, has a higher binding affinity for the human and functional potency for rat β- adrenoceptor subtypes than the racemate. However, in contrast to the catecholamines and formoterol, the functional potency of the racemic mixture and its (-)-enantiomer are not significantly different from their binding affinity, suggesting that they are examples of partial agonists with sufficient intrinsic activity to produce full agonist responses.

Synthesis of wiendendiol-A and wiedendiol-B from Labdane diterpenes

Two efficient enantiospecific syntheses of wiedendiol-A (1) from (-)- sclareol (7), via 11-bromo-8-drimene (11) and 8-drimen-11-al (3), are reported. The first enantiospecific synthesis of wiedendiol-B (2), via 85.95- driman-11-al (26), by two alternative routes starting from 7 and (+)-cis- abienol (8) is also described. 21 prepared from protocatchhualdehyde (17) was used as somatic synthon for preparing 1 and 2.

Enantiospecific synthesis of (+)-puupehenone from (-)-sclareol and protocatechualdehyde

The first enantiospecific synthesis of the antitumor and cholesteryl ester transfer protein (CETP) inhibitor (+)-puupehenone (19) from (-)-sclareol (10) and protocatechualdehyde (4) is described. The key steps of the reaction sequence are the organoselenium-induced cyclization of the mixture of regioisomers 15a-b to give 16 and 17, with complete diastereoselectivity, and the simultaneous removal of benzyl and phenylselenyl groups of 16 and 17 by treating with Raney Ni.