N-Boc-Nortropinone CAS 185099-67-6

BOC-NTP is a key intermediate for the synthesis of Tropine and its derivatives. Topiconazole is a type of alkaloid found in natural plants with a wide range of biological activities, including acting as an acetylcholine receptor antagonist for the treatment of diseases such as Parkinson's disease and gastrointestinal spasms. By regulating the transmission of the central nervous system, pain is relieved and inflammatory reactions are suppressed. Some derivatives of tropinol have interfering effects on insect nerve conduction and can be developed as biopesticides.

Example of synthetic pathway: BOC-NTP can be converted to demethyltropinone through deprotection (Boc) and reduction reactions, and further catalyzed hydrogenation or chemical reduction to obtain tropinol. Under acidic conditions (such as TFA/DCM), the Boc group is removed, resulting in the formation of demethylpyrrolidone. Reduce carbonyl groups using sodium borohydride (NaBH ₄) or lithium aluminum hydride (LiAlH ₄) to obtain tropinol derivatives.

The aromatic ring structure of BOC-NTP can be efficiently combined with halogenated aromatic hydrocarbons (such as bromobenzene) through Suzuki coupling reaction to form carbon carbon bonds and generate biphenyl compounds. This type of reaction has wide applications in the synthesis of drug molecules (such as anti-inflammatory drugs, antidepressants) and functional materials (such as fluorescent probes, organic optoelectronic materials). Using palladium catalyst (such as Pd (PPh3) ₄) as a medium, high yields (>85%) of coupling products can be achieved by reacting in alkaline conditions (such as K ₂ CO3 aqueous solution) and organic solvents (such as toluene/ethanol mixed solvent) at 80-100 ℃ for 12-24 hours.

Boc group is one of the commonly used amino protecting groups in peptide synthesis. Its stability is moderate and can be selectively removed under acidic conditions (such as TFA), while other functional groups (such as side chain protecting groups) are not affected. BOC-NTP can be used as a model compound to study the removal mechanism of Boc groups or optimize peptide synthesis processes. By introducing chiral centers, BOC-NTP can be converted into chiral ligands for catalyzing asymmetric synthesis reactions (such as asymmetric hydrogenation, asymmetric epoxidation) to generate compounds with optical activity. This type of reaction is of great significance in the total synthesis of natural products and asymmetric manufacturing of drugs.

The boronic acid group of BOC-NTP (after deprotection) can undergo reversible covalent binding with carbohydrate molecules (such as glucose) to form five - or six membered cyclic boronic acid esters. This property is used to design glucose responsive hydrogels to achieve intelligent insulin release. For example, N-Boc Nortropinone is modified on the surface of polyacrylamide hydrogel, and after deprotection, it combines with glucose to cause swelling of the hydrogel, thus controlling the rate of insulin release.

Its nitrogen and oxygen atoms can serve as coordination sites, binding with metal ions such as Zn ² ⁺ and Cu ² ⁺ to construct MOFs with specific pore structures and adsorption properties. This type of material has potential applications in gas storage (such as CO ₂ capture), catalysis (such as oxidation reactions), and drug delivery (such as controlled release carriers). N-Boc-Nortropinone can be used as a crosslinking agent to prepare crosslinked polymers (such as polyurethane and epoxy resins) by exposing amino or hydroxyl groups through deprotection reactions, enhancing the mechanical strength, heat resistance, or chemical stability of materials.

BOC-NTP, as a high-purity compound (purity ≥ 98%), is widely used as a standard for analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR), for instrument calibration, method validation, or compound identification. For example, in liquid chromatography-mass spectrometry (LC-MS) analysis, BOC-NTP can be used as an internal standard to correct sample matrix effects and improve quantitative accuracy.

In pharmacokinetic studies, BOC-NTP can be used as a model compound to investigate the mechanism of Boc group removal in vivo or the structural identification of metabolites. For example, by orally administering BOC-NTP to experimental animals, collecting urine and fecal samples, and analyzing metabolites using LC-MS technology, the removal pathway of Boc groups can be identified (such as acidic hydrolysis or enzyme catalysis).

The rigid three-dimensional conformation of tropane can reduce the recognition and binding of drug molecules to BBB efflux pumps, thereby reducing efflux rates. For example, the steric hindrance formed by the nitrogen atom and Boc group of tropane derivatives may hinder P-gp's recognition of its conformation and prolong the drug's retention time in the brain. In addition, the bridging ring structure of tropane can limit molecular flexibility, reduce conformational changes during metabolic processes, and maintain drug activity.

The introduction of Boc groups significantly altered the electron distribution of tropane. The carbonyl oxygen atom in the Boc group reduces the electron cloud density of nitrogen atoms through electron withdrawing effect, thereby reducing non-specific binding between drugs and plasma proteins and increasing the concentration of free drugs. At the same time, the tert butyl portion of the Boc group increases molecular lipophilicity through hydrophobic interactions, promoting its penetration through the BBB through passive diffusion. For example, the log P value (predicted value) of BOC-NTP may be higher than that of unprotected tropinone, thereby enhancing its brain permeability.

he Boc group can serve as a temporary protective group, which can be removed under acidic conditions after the drug reaches the target tissue, releasing the active tropane structure. This feature can be used to design brain targeted prodrugs:
Prodrug strategy: BOC-NTP is conjugated with brain targeted carriers (such as TfR antibodies, Angiopep-2 peptides), transported through the BBB via receptor-mediated transport, and subsequently deprotected in the acidic environment of the brain to release the active drug.
PH responsive release: Utilizing the acidic characteristics of the brain tumor microenvironment (pH 6.5-6.8), design Boc group modified nanoparticles to achieve precise drug release at the tumor site.

Tropidine derivatives have a wide range of applications in central nervous system drugs:
AntiParkinson's disease drug: Trihexyphenidyl binds to the M receptor through the structure of tropine to alleviate tremor symptoms. Its lipophilic modification (such as introducing chlorine atoms) significantly improves BBB penetration.
Antidepressant drugs: Amitriptyline's tropane skeleton binds to 5-HT transporters through hydrogen bonding, and its high lipid solubility (log P=3.1) makes it easy to penetrate the BBB and exert antidepressant effects.
Analgesic drugs: The tropane portion of morphine (Morphine) mediates analgesia through the μ - opioid receptor, and its metabolite, diacetylmorphine (Heroin), has higher lipid solubility and faster penetration through the BBB, but is more addictive.