线性脂代胺卡瓦拉胺A及其C25-表皮的总合成
Manas Ranjan Sahu1, Sudhir R Ingale1,2, Ravindar Kontham1,2
1Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune-411008, India. k.ravindar@ncl.res.in.
Organic & biomolecular chemistry
|January 14, 2025
概括
研究人员合成了kavaratamide A,一种来自蓝藻细菌的脂质和它的C25-epimer. 该研究详细介绍了立体选择性总合成,并评估了这两种化合物对癌症细胞系的细胞毒性.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 药用化学 医学化学
背景情况:
- 卡瓦拉胺A是一种从蓝藻菌*Moorena bouillonii*中分离出来的线性脂质.
- 菌是一种丰富的生物活性天然产品来源,具有潜在的治疗应用.
- 复杂的自然产品的立体选择性合成对于结构-活性关系研究和药物开发至关重要.
研究的目的:
- 为了实现kavaratamide A.A.的立体选择性总合成.
- 为了合成非自然的C25-epimer的kavaratamide A. A. 的合成.
- 为了评估kavaratamide A及其C25-epimer的细胞毒性活性.
主要方法:
- 采用了一个融合合成策略.
- 凯克的非对称合被用来构建性 (3S) -3-氧酸片段.
- 包括L-Val,N-Me-L-Ala, (S) -Hiva和 (S) -iPr-O-Me-pyr在内的片被使用优化的合方法组装在一起,以防止种族化.
主要成果:
- 成功实现了kavaratamide A的立体选择性总合成.
- 通过修改凯克合条件,可通过良好的产量合成kavaratamide A的C25-epimer.
- 在MTT试验中,kavaratamide A和C25-epi-kavaratamide A都对HepG2和PANC-1癌细胞系表现出中度的细胞毒性.
结论:
- 这项研究表明,一种可行的合成途径可用于kavaratamide A及其表皮质.
- 这些发现为复杂脂质的合成提供了宝贵的见解.
- 卡瓦拉胺A及其C25-epimer显示出作为细胞毒剂的潜力,需要进一步调查.
相关概念视频
03:00Preparation of Epoxides
7.7K
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy...
7.7K
01:27Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview
1.3K
Wilhelm Rudolph Fittig discovered the pinacol coupling reaction in 1859. It is a radical dimerization reaction and involves the reductive coupling of aldehydes or ketones in the presence of hydrocarbon solvent to yield vicinal diols.
1.3K
01:19α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
1.3K
The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an α-hydroxy ketone product. The α-hydroxy ketone is also called acyloin, so the reaction is referred to as ‘acyloin condensation.’
1.3K
01:27Aldol Condensation with β-Diesters: Knoevenagel Condensation
2.1K
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
2.1K
01:08Esters to β-Ketoesters: Claisen Condensation Mechanism
2.8K
Regular Claisen condensation involves the synthesis of β-ketoesters by combining identical ester molecules bearing two α hydrogens in the presence of an alkoxide base. The reaction commences with the deprotonation of the acidic α hydrogen by the base to form a resonance stabilized ester enolate. This nucleophilic ion then attacks the carbonyl center of another ester molecule to generate a tetrahedral alkoxide intermediate. Next, the expulsion of the alkoxide group from the...
2.8K
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
3.1K
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an...
3.1K