303191-35-7

Upstream product

• 104-53-0 3-phenyl-propionaldehyde 
• 60340-28-5 (S)-1-phenyl-5-hexen-3-ol 
• 3277-89-2 phenethylmagnesium bromide 
• 123-72-8 butyraldehyde 
• 2430-76-4 (R)-6-Phenyl-hexane-1,4-diol 
• 112607-22-4 (+)-(R)-5-(2-phenylethyl)dihydrofuran-2(3H)-one 
• 13122-67-3 6-phenyl-4-oxohexanoic acid 
• 14371-10-9 (E)-3-phenylpropenal 
• 138298-28-9 Acetic acid (R)-4-hydroxy-6-phenyl-hexyl ester 
• 927-77-5 n-propylmagnesium bromide 

Downstream Products

• 1346137-86-7 (15R,2S)-1-phenylhexan-3-yl 1-(2-oxo-2-phenylacetyl)piperidine-2-carboxylate 
• 1346137-85-6 (15S,2S)-1-phenylhexan-3-yl 1-(2-oxo-2-phenylacetyl)piperidine-2-carboxylate 
• 1421280-14-9 (15R,2S)-tert-butyl-1-phenylhexan-3-yl piperidine-1,2-dicarboxylate 

Relevant academic research and scientific papers

The precise chemical-physical nature of the pharmacore in FK506 binding protein inhibition: ElteX, a new class of nanomolar FKBP12 ligands

Due to its central role in immunosuppression and cell proliferation and due to its specific peptidyl-prolyl-isomerase (PPI) function, the FKBP protein family is at the crossroad of several important metabolic pathways. Members of this family, and notably FK506 binding protein (FKBP12), are thought to be involved in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, as well as in proliferation disorders and cancer. Using an interdisciplinary approach based on computational, synthetic, and experimental techniques, we show that the best potential binders for FKBP proteins optimally expose the two contiguous carbonyl oxygen in the proline-mimetic chain for FKBP docking and are characterized by the abundance of rigid quasi-cyclic structures stabilized in aqueous solution by intraligand hydrophobic interactions mimicking the macrolide structure of the natural FKBP binders FK506 and Rapamycin. These peculiar structural and chemical-physical features define at the same time an ElteX compound and the minimal pharmacore in the FKBP family, shedding new light on the isomerization mechanism of the PPI domain. On the basis of the above hypothesis, we have successfully designed and synthesized several nanomolar ElteX FKBP12 ligands. Among these, ElteN378 is a new low atomic weight ligand with affinity comparable to that of the macrolide Rapamycin.

Catalytic highly enantioselective alkylation of aldehydes with deactivated grignard reagents and synthesis of bioactive intermediate secondary arylpropanols

Because of the high reactivity of Grignard reagents, a direct, highly enantioselective Grignard reaction with aldehydes has rarely been disclosed. In this report, Grignard reagents were introduced with bis[2-(N,N′- dimethylamino)ethyl] ether (BDMAEE) to effectively deactivate their reactivity; thus, a highly enantioselective alkylation of aldehydes with Grignard reagents resulted from catalysis by (S)-BINOL-Ti(OiPr)2. It is thought that BDMAEE chelates the in situ generated salts MgBr2 from a Schlenk equilibrium of RMgBr and Mg(OiPr)Br from transmetalation of RMgBr with Ti(OiPr)4. The Mg salts can actively promote the undesired background reaction to give the racemate. The chelation definitely inhibits the catalytic activity of the Mg salts, suppresses the unwanted background reaction, and enables the highly enantioselective addition catalyzed by (S)-BINOL-Ti(OiPr)2. Consequently, the Mg salt byproducts were not removed, less Ti(OiPr)4 than RMgBr was used, and extremely low temperature was avoided in this catalytic asymmetric reaction in comparison with the research disclosed before. Various alkyl Grignard reagents were investigated in the asymmetric addition, and iBuMgBr resulted in the highest enantioselectivity, >99%. Furthermore, important intermediate secondary arylpropanols for chiral drug synthesis were effectively synthesized with high enantioselectivity, up to 97%, in one step.

Stereospecific reaction of α-carbamoyloxy-2-alkenylboronates and α-carbamoyloxy-alkylboronates with grignard reagents - Synthesis of highly enantioenriched secondary alcohols

Highly enantioenriched secondary alcohols were synthesized by treatment of α-carbamoyloxy-2-alkenylboronates and α-carbamoyloxy-alkylboronates with Grignard reagents. An intermediary boronate complex was transformed stereospecifically to the corresponding secondary 2-alkenyl- and alkylboronates by migration of an introduced residue. Oxidative workup furnished the enantioenriched secondary alcohols.

Enantioselective addition of Grignard reagents to aldehydes

The addition of Grignard reagents to aldehydes in the presence of chiral aminoal-cohols shows a moderate enantioselectivity. The study carried out with a series of ligands allows the correlation between the structural characteristics and their reactivity.

Enantioselective Preparation of sec. Alcohols from Aldehydes and Dialkyl Zinc Compounds, Generated in situ from Grignard Reagents, Using Substoichiometric Amounts of TADDOL-Titanates

Using the Schlenk trick (precipitation of MgX2 from etheral solutions by the addition of 1,4-dioxane) mixtures of a Grignard reagent RMgX (X = Cl, Br, I) and 0.5 equiv.ZnCl2 in Et2O can be converted to zinc alkyls R2Zn which in turn are added with enantioselectivities of up to 99:1 to aliphatic and aromatic aldehydes in the presence of Ti(OCHMe2)4 and a chiral titanate derived from an α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL).Grignard reagents containing remote double bonds, benzene rings, or acetal groups can also be employed.Different TADDOLs are compared with respect to their usefulness in this kind of enantioselective reactions.

Baker's yeast reduction of arylalkyl and arylalkenil γ- and δ-keto acids

γ- and δ-Lactones 5, 6, 13, 14, 15 and 16 were synthesized via baker's yeast reduction of the corresponding keto acids 3, 4 and 9-12. The enantioselectivity of the reduction is strongly dependent on the nature of the keto acid; the δ-lactones ware always obtained in an ee% higher than the γ-lactones and ranging from 70% to 100%.