月: 2023年6月

What Is Pinacol?

Pinacol is a divalent of alcohol and an important compound in organic chemistry.

Pinacol itself is sometimes used as an important intermediate in organic synthesis, and it is also the origin of the name of the pinacol rearrangement reaction. This rearrangement reaction proceeds under acid catalysis and converts an alcohol group to a ketone or aldehyde.

Uses of Pinacol

Pinacol is an important compound in organic synthesis and has a variety of uses.

1. Synthetic Intermediates

Pinacol is used as a synthetic intermediate for many organic compounds. In particular, the pinacol rearrangement reaction, in which pinacol is converted to ketones under an acid catalyst, is widely used in organic synthesis.

2. Protecting Group

The reaction of pinacol with aldehydes or ketones yields pinacol boronate esters, which can be used to protect the carbonyl group. Later, deprotection reactions under appropriate conditions regenerate the original aldehyde or ketone, which is useful for selective conversion of other moieties. 

3. Reducing Agent

Pinacol has a reducing ability and is particularly suitable for the reduction of alkyl halides, aldehydes, and ketones.

4. Chiral Ligands

Chiral ligands, such as pinacol acetate, are synthesized with pinacol and play an important role in catalytic asymmetric synthesis.

Properties of Pinacol

Pinacol (pinacol) has the chemical formula C6H14O2 and the IUPAC name is 2,3-dimethylbutane-2,3-diol.

It is a colorless crystalline or powdery solid with a distinctive sweet odor. Its melting point is 41-43°C and the boiling point is 171-172°C. It is somewhat soluble in water, but dissolves well in organic solvents such as ethanol and ether.

It is relatively stable against heat and light. However, it reacts with oxidants and strong acids, generating heat. It is recommended to store pinacol in closed containers in a cool and dry place.

Pinacol reacts with acids and bases to form a variety of compounds. For example, the pinacol rearrangement reaction, in which hydrolysis proceeds under acid catalysis to form ketones, is known. Pinacol plays an important role in synthetic organic chemistry and is used as a synthetic intermediate and protective group in the synthesis and conversion of a wide variety of compounds.

Structure of Pinacol

Pinacol is a type of bisecanediol in which two hydroxyl groups are bonded to adjacent carbon atoms. In the structure of Pinacol, the central four carbon atoms are arranged in a straight line, with a hydroxyl group attached to each of the two inner carbon atoms.

In its conformation, pinacol has two isomers (cis and trans). Both isomers are easily converted to each other by temperature and solvents, so cis-trans isomers are usually mixed.

This structure is the reason why pinacol exhibits unique chemical reactions. The pinacol rearrangement reaction is a typical example, in which adjacent hydroxyl groups react to form ketones, allowing the synthesis of a variety of ketones and the introduction of functional groups.

Other Information on Pinacol

Pinacol Production Methods

Pinacol is mainly produced by pinacol reduction, which is the reductive conversion of aldehydes and ketones to diols. Pinacol reduction is generally performed using metallic sodium or magnesium.

Aldehydes or ketones are dissolved in an appropriate solvent, such as ether or tetrahydrofuran. The aldehyde or ketone is then reduced using metallic sodium or magnesium. The metal is typically used in excess amounts.

During the reaction process, the sodium or magnesium is oxidized and the aldehyde or ketone is reduced to a divalent alcohol (pinacol). Once the reaction is complete, the reactants are cooled and the products are separated and purified by filtration or extraction.

Pinacol reduction is one of the reduction methods used in organic synthesis in many cases, allowing the efficient synthesis of divalent alcohols from aldehydes and ketones. However, this method requires caution because stereochemical control can be difficult and the products may react further in the presence of impurities.

What Is Vincristine?

Vincristine is an anticancer drug developed by Eli Lilly and Company, an American pharmaceutical company.

It is also known by the trade name Oncovin and is manufactured and marketed in Japan by Nippon Kayaku Co. It is a commonly used drug for hematologic tumors and is listed on the World Health Organization’s (WHO) Model List of Essential Medicines as an important drug.

Vincristine is found in the oleander plant in Nichinichiwa, and is chemically classified as a vinca alkaloid, a plant alkaloid. As an anticancer drug, it is classified as a microtubule polymerization inhibitor and is a deleterious drug.

As a drug, it is only prescribed by a physician and is administered intravenously. It is usually supplied as Vincristine sulfate. The CAS number is 2068-78-2.

Uses of Vincristine

1. Anticancer Agents

Vincristine is used as an anticancer agent. As a pharmaceutical product, Vincristine is indicated in Japan as of 2022 for the treatment of leukemia, malignant lymphoma pediatric oncology, multiple myeloma malignant astrocytoma, glioma with oligodendroglioma component in combination with other antineoplastic agents, and pheochromocytoma.

2. For Investigational Studies

Vincristine is also used as an anti-tumor agent for experimental research and as a reagent in cytoskeletal research when microtubule polymerization inhibition is performed. It is also sold as a reagent for experimental studies.

3. Therapeutic Use in Animals

Vincristine is sometimes used in the treatment of malignant lymphoma in dogs and other pet animals. In recent years, there has been a growing awareness of the possibility of somehow treating cancer in pet animals (with the hope of prolonging their lives).

Although Vincristine is not an official veterinary drug, there are currently no anti-cancer drugs for animals. Therefore, human drugs may be used by veterinarians.

Characteristics of Vincristine

Vincristine’s mechanism of action is the inhibition of microtubule polymerization. Mitosis of cells requires the formation of a spindle. The spindle is formed by the attachment of microtubules to chromosomes and the polymerization and depolymerization of microtubules to form a spindle thread.

Vincristine binds to microtubules and causes abnormalities in the structure and function of the spindle, resulting in the arrest of mitosis in the mid-mitotic (M) stage of the cell. The mitotic arrested cells are induced to apoptosis.

In this way, tumor cell proliferation is suppressed and the cells are killed. However, since it also inhibits cell division of normal cells, the concern is that it affects not only tumor cells but also normal cells. This can cause side effects.

Other Information About Vincristine

1. Side Effects of Vincristine

Vincristine also inhibits cell division of normal cells, which may cause side effects such as hair loss (alopecia) and a decrease in white blood cell count (myelosuppression). This is a common characteristic of anticancer agents.

Peripheral neuropathy is also known as a frequent side effect. Clinically, this is felt as numbness in the hands and feet and loss of sensation in the fingers. This symptom can have a significant impact on the lives of those undergoing treatment, such as difficulty in performing personal tasks and burns or injuries due to lack of sensation.

There is also a high likelihood that the condition will worsen with continued administration. Therefore, dosage should be reduced or discontinued when this symptom is observed.

Peripheral neuropathy is also seen with other phytoalkaloid microtubule polymerization inhibitors and is thought to be due to the drug also binding to the microtubules of peripheral nerves, causing axonal degeneration. Another common side effect is constipation.

2. Vincristine and Multiple Therapy

Vincristine is often used in combination with other anticancer agents that have different mechanisms of action. The objective is to inhibit the growth of cancer effectively by having multiple actions work simultaneously.

For example, in lymphoma, it is used in combination with cyclophosphamide, which methylates DNA, doxorubicin, which gets between DNA structures, and oxaliplatin, which forms cross-links in DNA. Because anticancer drugs have strong side effects, the actual dosage of combination therapy used is carefully considered and determined.

What Is Vinblastine?

Vinblastine is a compound classified as a vinca alkaloid, a type of alkaloid isolated from the plant Nichinichiwa.

Its molecular weight is 810.975 and its molecular formula is C46H58N4O9. The compound is characterized by its white to light yellow powdery color and extremely low water solubility. It is virtually insoluble in water and alcohols and soluble in organic solvents such as DMSO and ethyl acetate.

Vinblastine is used as an antineoplastic agent in the treatment of cancer because of its ability to inhibit cell proliferation by blocking microtubule polymerization during the M phase of cell division. Vinblastine, used as a drug, is generally in a sulfate structure to improve stability and solubility.

Uses of Vinblastine

Vinblastine is a type of antineoplastic agent used in the treatment of cancer. After being administered intravenously, vinblastine is taken up into the cells by taking advantage of its high liposolubility.

It then acts specifically in the M phase of the cell cycle, preventing cancer cells from dividing by inhibiting the binding of tubulin, a protein that makes up microtubules within the cell. Vinblastine is one of the leading anticancer drugs and is used against a wide range of cancer types, including leukemia, malignant lymphoma, breast cancer, ovarian cancer, and lung cancer.

Because vinca alkaloids are characterized by their tendency to cause neuropathy, patients should be aware of numbness in the fingers and toes and abnormal sensations in the skin when Vinblastine is administered.

Properties of Vinblastine

Vinblastine is a white to light yellow powder. It has extremely low solubility and is virtually insoluble in solvents such as water, ethanol, and methanol. On the other hand, it is soluble in organic solvents such as DMSO, dichloromethane, and ethyl acetate, and is generally used in these solvents.

Vinblastine is not metabolized in vivo and is excreted directly into the urine, and its pharmacokinetics are believed to involve fibroblast growth factor receptor (FGFR) 3. It is also a highly toxic alkaloid and should be used with caution.

Structure of Vinblastine

The molecular structure of Vinblastine is an indole alkaloid with an indole skeleton in its basic structure. Its chemical formula is C46H58N4O9 and its molecular weight is 810.97.

It has a complex structure consisting of several chiral carbon atoms and numerous oxygen and nitrogen atoms, and has several functional groups such as alkyl and carboxyl groups on its side chains. It has several functional groups, such as alkyl groups and carboxyl groups on its side chains. Due to its high liposolubility, vinblastine is taken up into cells and binds to tubulin, a dimer, thereby exerting anticancer effects and inhibiting cancer cell proliferation.

Vinblastine is extracted from plants, but many optical isomers are known to exist in natural products. Therefore, there is a need to develop methods for the synthesis and purification of purely active and advantageous optical isomers.

However, the current challenge is the low yield due to the difficulty of synthesis caused by the complex structure. There is a continuing need to develop more efficient synthetic methods for Vinblastine.

Other Information on Vinblastine

How Vinblastine Is Produced

Vinblastine is isolated from Madagascar periwinkle (Catharanthus roseus) along with its precursors (catharanthine and vindoline). Vinblastine is extracted from leaves, stems, and roots, and is isolated by chromatographic purification.

Due to its complex three-dimensional structure, the many steps involved in its synthesis, and low yields caused by byproducts, it is difficult to synthesize vinblastine on an industrial scale, and extraction from natural products is the main source of vinblastine.

However, because plant-extracted Vinblastine and its precursors contain optical isomers that are unfavorable for activity, enantioselective total synthesis using chiral agents (sharpless catalysts) and controlled reaction temperatures have recently received considerable attention.

What Is Bilirubin?

Bilirubin is an organic compound that is a metabolite of heme (heme iron).

It has the chemical formula C₃₃H₃₆N₄O₆ and a chain-like molecular structure consisting of four pyrrole rings connected in a linear chain. In humans and animals, it is excreted through bile and urine.

It has a molecular weight of 584.66 and a melting point of 192°C. It is a reddish yellow to yellowish red powder at room temperature. It is almost insoluble in water, but soluble in benzene, chloroform, chlorobenzene, carbon disulfide, acids, and alkalis. It is slightly soluble in ethanol and ether.

Uses of Bilirubin

Bilirubin levels are used as an indicator of liver function in blood tests. Bilirubin before being processed by the liver is called indirect bilirubin, and after being processed is called direct bilirubin: the sum of both is called total bilirubin.

The normal level of total bilirubin is 0.2 to 1.2 mg/dL, and when this level is exceeded, hepatitis, cirrhosis, and liver cancer disease are suspected. Bilirubin is a pigment formed when hemoglobin in red blood cells breaks down.

Bilirubin is processed (conjugated) in the liver and excreted as bile in the duodenum, but when liver function is impaired, bilirubin cannot be processed, and a large amount of bilirubin remains in the blood. This is called jaundice, which is a yellowing of the skin, sclera, and mucous membranes.

Even though bilirubin is a pigment molecule, it is not widely used as a pigment. It is found in animal bile and is sometimes used in various studies.

Characteristics of Bilirubin

Bilirubin has an open chain-like structure with four pyrrole rings and is classified as a type of tetrapyrrole. This structure contrasts with the four pyrroles, forming a large porphyrin ring in heme.

It functions as a dye molecule and has an absorption maximum wavelength of 451-455 nm. Bilirubin is very similar in structure to phycobilin, a pigment used by seaweeds to absorb light.

It is also known that when exposed to light, the double bond in bilirubin is isomerized, increasing its water solubility, and this has been applied in phototherapy to treat neonatal jaundice.

Types of Bilirubin

Bilirubin in vivo is divided into two types: before it is transported to the liver (indirect bilirubin) and after it is processed by the liver (direct bilirubin).

Although bilirubin is a biological substance, it is also sold as an isolated compound. It is generally sold as a reagent product for research and development, which requires refrigeration (-20°C) for storage and transport. It is available in quantities of 100 mg and 1 g.

Other Information on Bilirubin

Metabolism of Bilirubin

Senescent or damaged red blood cells are broken down in the spleen. Bilirubin is a breakdown product of heme, a major component of red blood cells which is metabolized during this process.

Heme is broken down into biliverdin by heme oxygenase (HMOX) and biliverdin is reduced by the action of biliverdin reductase, leading to bilirubin.

Bilirubin is then transported to the liver by binding to a plasma protein, albumin, where it undergoes glucuronidation by glucuronyltransferase in the liver.

The conjugation makes bilirubin more soluble in water. This reaction is mediated by uridine diphosphate-glucuronyltransferase (UDPGUTF). Bilirubin is secreted by the liver in this form as bile.