81395-28-0

Upstream product

• 20194-18-7 sodium phenyl-methanolate 
• 3433-80-5 1-Bromo-2-bromomethyl-benzene 
• 18982-54-2 o-bromobenzyl alcohol 
• 100-39-0 benzyl bromide 
• 100-52-7 benzaldehyde 
• 6630-33-7 ortho-bromobenzaldehyde 
• 100-51-6 benzyl alcohol 

Downstream Products

• 119367-65-6 2-<(Benzyloxy)methyl>benzaldehyde 
• 1456722-48-7 [(R)-1-(2-benzyloxymethyl-benzoyl)-3-(3,4-di methoxyphenyl)-propyl]-carbamic acid benzyl ester 
• 276888-00-7 indan-2,2-dicarboxylic acid, dimethyl ester 
• 1354017-72-3 (R)-2-(2-((benzyloxy)methyl)benzamido)-3-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)-thio)propanoic acid 
• 1354017-82-5 C₃₄H₄₅NO₄S 
• 119367-89-4 2-<(Benzyloxy)methyl>benzoic acid 
• 104454-05-9 dimethyl 2,6-dimethyl-4-(2-tosyloxymethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 104454-04-8 dimethyl 2,6-dimethyl-4-(2-hydroxymethylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 252554-72-6 (2R,5R)-1-(2-Benzyloxymethyl-phenyl)-2,5-dimethyl-phospholane 
• 252554-75-9 2-benzyloxymethyl-phenyl-phosphane 
• 420838-26-2 2'-benzyloxymethyl-2,6-bis-methoxymethoxy-biphenyl 
• 252554-74-8 (2-benzyloxymethyl-phenyl)-phosphonic acid diethyl ester 

Relevant academic research and scientific papers

Silver(I)-Catalyzed Reductive Cross-Coupling of Aldehydes to Structurally Diverse Cyclic and Acyclic Ethers

A range of medium-sized cyclic ethers (5 to 11 membered) have been effectively synthesized through intramolecular reductive coupling of dialdehydes initiated by 50 ppm to 0.5% of AgNTf2 with hydrosilane at 25 °C. The catalytic system is also suitable for the coupling of two different monoaldehydes to provide unsymmetrical ethers. This protocol features broad functional group compatibility, high product diversity, high efficiency, and utility in the late-stage modification of complex biorelevant molecules.

Divergent Access to Seven/Five-Membered Rings Based on [1,6]-Hydride Shift/Cyclization Process

We have achieved a divergent access to seven/five-membered rings based on a [1,6]-hydride shift/cyclization process from benzylidenemalonate with an o-alkoxymethyl group. Whereas Yb(OTf)3 afforded benzoxepines (with a seven-membered ring) selectively, indanes (with a five-membered ring) were the main products when Sc(OTf)3 was employed.

Reductive Etherification of Aldehydes and Ketones with Alcohols and Triethylsilane Catalysed by Yb(OTf)3: an Efficient One-Pot Benzylation of Alcohols

The one-pot synthesis of symmetrical and unsymmetrical ethers from aldehydes and ketones can be conveniently performed using Yb(OTf)3 as catalyst and triethylsilane as reducing agent in presence of alcohols. This methodology leads to the synthesis of ether derivatives with good yields. Notably, this process resulted a useful tool to protect alcohols as benzyl ether derivatives using differently substituted benzaldehydes as protecting agents under mild conditions. A plausible mechanism was also proposed. (Figure presented.).

Au-catalyzed biaryl coupling to generate 5- to 9-membered rings: Turnover-limiting reductive elimination versus π-complexation

The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes-substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to π-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the π-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.

Au-Catalyzed Biaryl Coupling to Generate 5- To 9-Membered Rings: Turnover-Limiting Reductive Elimination versus ?-Complexation

The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes - substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to ?-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the ?-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.

Triarylphosphine ligands with hemilabile alkoxy groups: Ligands for nickel(II)-catalyzed olefin dimerization reactions. hydrovinylation of vinylarenes, 1,3-dienes, and cycloisomerization of 1,6-dienes

Substitution of one of the phenyl groups of triphenylphosphine with a 2-benzyloxy-, 2-benzyloxymethyl- or 2-benzyloxyethyl-phenyl moiety results in a set of simple ligands, which exhibit strikingly different behaviour in various nickel(II)-catalyzed olefin dimerization reactions. Complexes of ligands with 2-benzyloxyphenyl- and 2-benzyloxymethylphenyldiphenylphosphine (L5 and L6, respectively) are most active for hydrovinylation (HV) of vinylarenes, with the former leading to extensive isomerization of the primary 3-aryl-1-butenes into the conjugated 2-aryl-2-butenes even at -55 °C. However, 2-benzyloxymethyl-substituted ligand L6 is slightly less active, affording up to quantitative yields of the primary products of HV at ambient temperature with no trace of isomerization, thus providing the best option for a practical synthesis of these compounds. In sharp contrast, hydrovinylation of a variety of 1,3-dienes is best catalyzed by nickel(II) complexes of 2- benzyloxyphenyldiphenylphosphine, L5. The other two ligands, 2-benzyloxymethyl- (L6) and 2-benzyloxyethyldiphenylphosphine (L7) are much less effective in the HV of 1,3-dienes. Nickel(II)-catalyzed cycloisomerization of 1,6-dienes into methylenecyclopentanes, a reaction mechanistically related to the other hydrovinylation reactions, is also uniquely effected by nickel(II) complexes of L5, but not of L6 or L7. In an attempt to prepare authentic samples of the methylencyclohexane products, nickel(II) complexes of N-heterocyclic carbene ligands were examined. In sharp contrast to the phosphines, which give the methylenecyclopentanes, methylenecyclohexanes are the major products in the (N-heterocyclic carbene)nickel(II)-mediated reactions.

COMPOUNDS AND METHODS FOR USE IN TREATING NEOPLASIA AND CANCER

The present invention relates to a novel method for the treatment of neoplasia, including cancer and other diseases and conditions in humans and mammals. More particularly, in preferred aspects, the present invention provides a method for the use of novel compounds for the treatment of neoplasia, hyperproliferative cell growth including psoriasis, restenosis following cardiovascular surgery, hyperplasia, including renal hyperplasia, chronic inflammatory diseases including rheumatoid and osteoarthritis, among others.

Amide-modified prenylcysteine based Icmt inhibitors: Structure-activity relationships, kinetic analysis and cellular characterization

Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme responsible for the α-carboxyl methylation of the C-terminal isoprenylated cysteine of CaaX proteins, including Ras proteins. This specific posttranslational methylation event has been shown to be important for cellular transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt inhibitors as potential anti-cancer agents. Previous analog studies based on N-acetyl-S-farnesylcysteine identified two prenylcysteine-based low micromolar inhibitors (1a and 1b) of hIcmt, each bearing a phenoxyphenyl amide modification. In this study, a focused library of analogs of 1a and 1b was synthesized and screened versus hIcmt, delineating structural features important for inhibition. Kinetic characterization of the most potent analogs 1a and 1b established that both inhibitors exhibited mixed-mode inhibition and that the competitive component predominated. Using the Cheng-Prusoff method, the K i values were determined from the IC50 values. Analog 1a has a KIC of 1.4 ± 0.2 μM and a KIU of 4.8 ± 0.5 μM while 1b has a KIC of 0.5 ± 0.07 μM and a KIU of 1.9 ± 0.2 μM. Cellular evaluation of 1b revealed that it alters the subcellular localization of GFP-KRas, and also inhibits both Ras activation and Erk phosphorylation in Jurkat cells.

Hydrovinylation of 1,3-dienes: A new protocol, an asymmetric variation, and a potential solution to the exocyclic side chain stereochemistry problem

Cyclic and acyclic 1,3-dienes undergo efficient (substrate/catalyst = 72) heterodimerization with ethylene in the presence of a Ni catalyst prepared from [o-(PhCH2O)]C6H4PPh2, [(allyl)2NiBr]2, and Na+ BAr4- (Ar = 3,5-bis-trifluromethylphenyl), giving 1,2-addition products. Yields up to 99% can be realized for several 1-vinylcycloalkenes and 1-substituted 1,3-butadienes. Phospholanes with suitably placed hemilabile ligating groups and phosphoramidites derived from binaphthol are excellent ligands for an asymmetric variation of this reaction, the latter giving 99% yield and >95% ee's for selected substrates. An example of how an exocyclic chiral center can be used to install other stereo-centers in the ring (e. g., the carbon to which the side chain is attached) is also provided. These discoveries open an expeditious entry into several biologically relevant classes of compounds, especially those carrying tetrahydronaphthalene and related heterocyclic moieties. Copyright

Cycloaromatization of a non-conjugated polyenyne system: Synthesis of 5H-benzo[d]fluoreno[3,2-b]pyrans via diradicals generated from 1-[2-{4-(2-alkoxymethylphenyl)butan-1,3-dinyl}]phenylpentan-2,4-diyn -1-ols and trapping evidence for the 1,2-didehydrobenzene diradical

Non-conjugated tetraynes 1 undergo thermal intramolecular cyclization to non-benzenoid diradicals (23) followed by radical cycloaromatization at 25°C to provide 7-dehydro-5H-benzo[d]fluoreno[3,2-b]pyran monoradical (24) and alkyl radicals (25). Hydrogen abstraction of 24 gives 5H-benzo[d]fluoreno[3,2-b]pyrans (3) which are converted to 4 by reaction with 25. On the other hand, 2 gives 5H-fluorenol (5), indicating the formation of 1,2-didehydrobenzene diradical intermediates (28 and 29). These radicals are trapped as the corresponding Diels-Alder-type products by reaction with an aromatic diene, anthracene.