51065-67-9

Upstream product

• 25112-78-1 2-methyl-2-(3-oxobutyl)-1,3-cyclopentanedione 
• 765-69-5 2-Methylcyclopentane-1,3-dione 
• 78-94-4 methyl vinyl ketone 
• 344-25-2 D-Prolin 
• 875542-94-2 (S)-N-(3,5-bis(trifluoromethyl)phenyl)pyrrolidine-2-carboxamide 
• 5870-63-3 3-hydroxy-2-methyl-2-cyclopenten-1-one 
• 51-35-4 4-hydroxyproline 

Downstream Products

• 325780-47-0 (3aS,5S,7aS)-3a,5-Dihydroxy-7a-methyl-5-phenyl-octahydro-inden-1-one 
• 218786-50-6 (3aS,5R,7aS)-3a,5-Dihydroxy-7a-methyl-5-phenyl-octahydro-inden-1-one 
• 500757-99-3 (3aS,7aS)-3a-hydroxy-7a-methyl-5-nitromethyl-2,3,3a,6,7,7a-hexahydro-1H-inden-1-one 

Relevant academic research and scientific papers

Construction of key building blocks towards the synthesis of cortistatins

This work reports the construction of key building blocks towards the synthesis of cortistatins; a family of steroidal alkaloids. Cortistatin A, being a primary target due to its superior biological properties over other congeners, has been prepared by two different synthetic routes. Synthesis of the precursor to the heavily substituted A-ring starting from d-glucose and construction of the DE-ring junction employing a Hajos-Parrish ketone as a chiral pool have been demonstrated. Efforts are underway to assemble these key fragments and build towards the total synthesis of cortistatin A.

Metal Coordination Controlled and Bifunctional H-Bonded Catalysis in Stereoselective Intramolecular Aldol Cyclizations toward Carbocyclic Tertiary β-Ketols

The principle of bifunctional catalysis is shown in the highly regio- and stereoselective intramolecular aldolization of 2-methyl-1,3-cyclopentanedione, C2-substituted with a methyl ethyl ketone group, to provide [3.2.1]-bicyclooctanol diones in the presence of catalytic amounts of either LiBr and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Mechanistic investigations corroborated by DFT calculations show that LiBr engages in a bifunctional coordination of two carbonyl moieties and leads to the preorganization of the reactive enolate intermediate for a base-mediated intramolecular aldol cyclization. On the other hand, TBD catalysis of the triketone substrate proceeds through a bifunctional H-bonded mechanism to give the same aldol product as the major diastereomer. The LiBr and TBD-catalyzed highly stereocontrolled intramolecular aldol cyclizations can be extended to other di- and triketones to give carbocyclic and carbobicyclic products as single diastereomers.

Bifunctional organocatalysts based on a carbazole scaffold for the synthesis of the Hajos-Wiechert and Wieland-Miescher ketones

Several bifunctional organocatalysts based on a carbazole scaffold containing a chiral amine and a synthetic oxyanion-hole have been synthesized and successfully applied to the synthesis of the Hajos-Wiechert and Wieland-Miescher ketones (up to 99% ee). Both enamine activation and H-bonding donor ability of these catalysts were evaluated by preparing catalysts differing in the nature of the amine [(R,R)-cyclohexanediamine or l-proline], the H-bond donor functional group (sulfonamide or amide) and the number of NH bonds. Modeling studies and an X-ray structure fully support the obtained results.

Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin

Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations are provided. Two and a half molecules: Astellatol and nitidasin are polycyclic sesterterpenoids, posing considerable challenges for synthetic chemists. In this full account, the evolution of a synthetic strategy for these and structurally related natural products is given (see scheme). The presented work includes efforts toward a biomimetic synthesis of astellatol, a successful route for the first total synthesis of (-)-nitidasin, and quantum-mechanical investigations into unexpected diastereosectivities.

Novel supported and unsupported prolinamides as organocatalysts for enantioselective cyclization of triketones

A novel prolylsulfonamide derived from ethylene diamine and its supported counterpart has been prepared and tested as enantioselective intramolecular aldol reaction of cyclic and acyclic triketones. Good to excellent yields and enantioselectivities have been obtained in water and under solvent free conditions.

The A-CD analogue of 16β,17α-estriol is a potent and highly selective estrogen receptor β agonist

Selective estrogen receptor β (ERβ) agonists display neuroprotective properties in animal models and hold promise in the treatment of neurodegenerative diseases. In our quest to design, synthesize and evaluate potent and safe ERβ agonists, we focused on m

A-CD estrogens. I. substituent effects, hormone potency, and receptor subtype selectivity in a new family of flexible estrogenic compounds

Long-term use of estrogen supplements by women leads to an increased risk of breast and uterine cancers. Possible mechanisms include metabolism of estradiol and compounds related to tumor-initiating quinones, and ligand-induced activation of the estrogen receptors ERα and ERβ which can cause cancer cell proliferation, depending on the ratio of receptors present. One therapeutic goal would be to create a spectrum of compounds of variable potency for ERα and ERβ, which are resistant to quinone formation, and to determine an optimum point in this spectrum. We describe the synthesis, modeling, binding affinities, hormone potency, and a measure of quinone formation for a new family of A-CD estrogens, where the A-C bond is formed by ring coupling. Some substituents on the A-ring increase hormone potency, and one compound is much less quinone-forming than estradiol. These compounds span a wide range of receptor subtype selectivities and may be useful in hormone replacement therapy.

Proline imidazolidinones and enamines in Hajos-Wiechert and Wieland-Miescher ketone synthesis

Readily available aromatic prolinamides obtained from the acid chloride of proline hydrochloride and anilines induce large enantiomeric excesses in intramolecular aldol condensations. Imidazolidinones derived from the reaction of the catalyst and enamines

N-Tosyl-(Sa)-binam-L-prolinamide as highly efficient bifunctional organocatalyst for the general enantioselective solvent-free aldol reaction

N-Tosyl-(Sa)-binam-L-prolinamide (5 mol%) and benzoic acid (1 mol%) were used as catalysts in the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-free conditions in the presence or absence of water. Under these reaction conditions it was possible to reduce the amount of required ketone to two equivalents to give the corresponding aldol products with high yields, regio-, diastereo- and enantioselectivities. The aldol reaction between aldehydes or the intramolecular aldol reaction can be also performed with excellent results. Georg Thieme Verlag Stuttgart.