通过动态分辨率和其生物活性合成P-类固醇氧化物不对称的合成
Long Yin1, Jiajia Li1, Changhui Wu2
1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Nature communications
|March 22, 2024
概括
这项研究引入了一种新的催化方法,用于制造enantiopure P-类固醇基基和基. 这些化合物显示出治疗自身主导性多囊性病 (ADPKD) 的潜力.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 催化剂是一种催化剂.
背景情况:
- 作为性联体和生物活性分子,P-类固醇异环非常重要.
- 不对称合成P-类固醇基衍生物带来了重大挑战.
研究的目的:
- 为芬醇氧化物开发一种催化动态分辨率.
- 为了获得纯净的P-类固醇芬丹和芬醇衍生物.
- 探索这些化合物的治疗潜力,以治疗自身主导性多囊性病 (ADPKD).
主要方法:
- 催化散立体和选择性结合物添加.
- 芬醇氧化物的动态分辨率.
- 在体外和体内测试合成化合物的ADPKD治疗疗效.
主要成果:
- 实现了高效率 (s系数>1057) 和出色的立体选择性 (dr>20:1,ee>99%).
- 证明了开发方法的广泛基质范围.
- 鉴定出化合物3az在体外和体内是囊生长的显著抑制剂.
结论:
- 这项研究提出了一种有效的方法,用于合成enantiopureP-类固醇异环.
- 化酸氧化物作为ADPKD的治疗剂显示出希望.
- 这项工作推进了非对称合成,并激发了对P-类固醇化合物的新药发现工作.
相关概念视频
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.1K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.1K
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
3.9K
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
3.9K
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
4.6K
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.
4.6K
Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
3.4K
The Wittig reaction, which converts aldehydes or ketones to alkenes using phosphorus ylides, proceeds through a nucleophilic addition‒elimination process.
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
3.4K
Sharpless Epoxidation
4.0K
The conversion of allylic alcohols into epoxides using the chiral catalyst was discovered by K. Barry Sharpless and is known as Sharpless epoxidation. The use of a chiral catalyst enables the formation of one enantiomer of the product in excess. This chiral catalyst is mainly a chiral complex of titanium tetraisopropoxide and tartrate ester (specific stereoisomer). The stereoisomer used in the chiral catalyst dictates the formation of the enantiomer of the product. In other words, the use of...
4.0K
Regioselectivity and Stereochemistry of Hydroboration
8.1K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
8.1K

![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
