片的14-氧化:可代因的催化直接自氧化为14-基可代因
Qibo Zhang1, Joseph O Rich, Ian C Cotterill
1Albany Molecular Research, Inc., Bioscience Division, Albany, New York 12212-5098, USA.
Journal of the American Chemical Society
|May 19, 2005
概括
研究人员开发了一种新方法来合成14-氧化片药物. 这一过程使用催化空气氧化,将编码氧化为14-基编码,从丰富的编码中实现直接合成.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 生物催化剂是一种生物催化剂.
背景情况:
- 合成14-基化阿片类药物通常依赖于thebaine作为起始材料.
- 微生物转化研究表明,可代因的14-基化可能涉及化学步骤而不是酶步骤.
研究的目的:
- 开发一种直接和高效的化学合成从codeinone14-hydroxycodeinone的合成.
- 探索使用可代因作为14-基化片合成的更容易获得的前体.
主要方法:
- 在水溶液中对codeinone的催化空气氧化.
- 使用简单的和铜盐 (如MnSO4,KMnO4,CuSO4) 作为催化剂.
- 加入一种降解剂,如硫酸盐,以管理过氧化物中间体.
主要成果:
- 通过催化空气氧化,Codeinone被有效地转化为14-hydroxycodeinone.
- 和铜盐证明了作为这种转化催化剂的有效性.
- 反应在水溶液中进行,提供了一个潜在的更绿色的合成路径.
结论:
- 这种方法提供了直接通往14-hydroxycodeinone的途径,绕过了对thebaine中间体的需求.
- 它允许利用更丰富的前体可代因合成14-氧化片药物.
- 这些发现挑战了以前关于编码素14-基化酶性质的假设,突出了其化学基础.
相关概念视频
Autoxidation of Ethers to Peroxides and Hydroperoxides
Ethers represent a class of chemical compounds that become more dangerous with prolonged storage because they tend to form explosive peroxides when standing in the air. Autoxidation is the spontaneous oxidation of a compound in air. In the presence of oxygen, ethers slowly oxidize to form hydroperoxides and dialkyl peroxides.
Free-Radical Chain Reaction and Polymerization of Alkenes
The conversion of alkenes to macromolecules called polymers is a reaction of high commercial importance. The structure of the polymer is defined by a repeating unit, while the terminal groups are considered insignificant. The average degree of polymerization represents the number of repeating units in the polymer molecule and is denoted by the subscript n.
Oxidation of Phenols to Quinones
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
Radical Autoxidation
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
Chain Reactions
Chain reactions involve highly reactive transient species, such as atoms or free radicals, as intermediates. These intermediates facilitate rapid reactions over an extended period. The process includes a series of steps: a reactive intermediate is consumed, reactants are converted to products, and the intermediate is regenerated. This cycle enables continuous repetition, amplifying the production of products with a small amount of intermediate. Chain reactions often utilize free radicals as...
Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).


