134078-23-2

Upstream product

• 53578-15-7 cubane-1-carboxylic acid 
• 111873-46-2 4-iodopentacyclo[4.2.0.0(2,5).0(3,8).0(4,7)]octane-1-carboxylic acid 
• 163332-87-4 4-iodopentacyclo[4.2.0.0(2,5).0(3,8).0(4,7)]octane-1-methanol 
• 24539-28-4 4-(methoxycarbonyl)-1-cubanecarboxylic acid 
• 29412-62-2 cubane-1,4-dicarboxylic acid dimethyl ester 
• 29412-63-3 monocarbomethoxycubane 
• 122200-58-2 4-iodopentacyclo[4.2.0.0^2,5.0^3,8.0^4,7]octane-1-carboxylic acid 
• 501909-90-6 bis-cubylmethyldialkoxy disulfide 
• 23096-16-4 methyl cubane 

Downstream Products

• 134078-21-0 [1-Cuban-1-yl-meth-(Z)-ylidene]-((2R,3R)-2,3-diphenyl-aziridin-1-yl)-amine 

Relevant academic research and scientific papers

The preparation and fate of cubylcarbinyl radicals

The cubylcarbinyl radical has been generated from cubylcarbinyl bromide and from the N-hydroxy-2-pyridinethaione ester of cubylacetic acid under various conditions favoring hydrogen-atom transfer to the radical. Only when selenophenol in high concentration is used as the hydrogen donor is any methylcubane formed. Otherwise the cubylcarbinyl radical rearranges. There is no evidence of a 1,2-shift into the homocubyl system. Instead, one, two, or three bonds of the cubane nucleus cleave, leading to a variety of olefinic products. For the most part, these have been characterized. A mechanistic scheme accounting for their formation is presented; sequential σ-bond breaking occurs regioselectively, favoring processes in which there is good overlap between the radical orbital and that of the breaking bond. The distribution of products is shown to depend qualitatively on the time the radical intermediates are let live, that is, on the concentration and effectiveness of the hydrogen atom transfer agent. From product distributions, the rate constant for ring cleavage of cubylcarbinyl radical is calculated to be at least 2 × 1010 s-1, substantially greater than that of any radical derived to date from a saturated hydrocarbon system. Methodology is given for the synthesis of cubylcarbinol, cubylacetic acid, 1,4-bis(hydroxymethyl)cubane, methylcubane, and a variety of other new cabane compounds.

Cyclooctatetraene: A Bioactive Cubane Paradigm Complement

Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery.

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

The scope and limitations of Eaton's rhodium(I)-catalyzed valence isomerization of cubane to cyclooctatetraene (COT) were investigated in the context of functional group tolerability, multiple substitution modes and the ability of cubane-alcohols to undergo one-pot tandem Ley–Griffith Wittig reactions in the absence of a transition metal catalyst.

Enantioselective synthesis of (: R)-2-cubylglycine including unprecedented rhodium mediated C-H insertion of cubane

The first enantioselective synthesis of (R)-2-cubylglycine, an analogue of (R)-2-phenylglycine in which the phenyl ring has been replaced by cubane, is disclosed. The key step was a telescoped Strecker reaction using (S)-2-amino-2-phenylethanol as a chiral auxiliary. Exploration of an alternative synthetic approach resulted in unprecedented cubane C-H insertion.

The cubane paradigm in bioactive molecule discovery: Further scope, limitations and the cyclooctatetraene complement

The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.

Cubanes in medicinal chemistry: Synthesis of functionalized building blocks

A collection of novel, pharmaceutically relevant cubane-containing molecules has been prepared from the commercially available cubane-1,4- dimethylester. A range of synthetic methods have been applied to prepare these cubane building blocks with one or two functional handles to allow easy incorporation into existing medicinal chemistry programs.

7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (σ2) receptor ligands

A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12-17 and 22-25) and similarly substituted pyrrolidines (32-36 and 41-44) were synthesized as sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived σ ligands. In vitro competition binding assays against σ receptors revealed that arylalkyl N-substituents conferred selectivity for the σ2 subtype, while alicyclic or polycarbocyclic substituents imparted high affinity for both subtypes. The σ2 binding and subtype selectivities of N-arylalkyl-7-azanorbornanes was generally greater than the analogously-substituted pyrrolidines, indicating that steric bulk and conformational restriction around the nitrogen atom are likely important for subtype discrimination.

Dialkoxy disulfides from cubycarbinols

Two dialkoxy disulfides 2 and 3 have been synthesized in respectable yields. The behaviour of 2 and 3 under thermal and photolytic conditions has been examined and we report the first examples of S2 liberation from aliphatic dialkoxy disulfides.

Effective synthetic routes to cubylcarbinol derivatives

Three alternative routes for the synthesis of cubylcarbinol (1) from 4-iodocubanecarboxylic acid (5) are described.

Cytochrome P450-catalyzed hydroxylation of mechanistic probes that distinguish between radicals and cations. Evidence for cationic but not for radical intermediates

Oxidation of the mechanistic probes trans,trans-2-methoxy-3- phenylmethylcyclopropane and methylcubane by six cytochrome P450 isozymes has been studied. The probes differentiate between radical and cationic species in that different structural rearrangeme