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Review

Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents

by
Yi Mou
1,*,†,
Shuai Wen
1,†,
Hong-Kai Sha
1,
Yao Zhao
1,
Li-Juan Gui
1,
Yan Wang
1 and
Zheng-Yu Jiang
2,*
1
College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou 225300, China
2
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceuticals 2024, 17(10), 1403; https://doi.org/10.3390/ph17101403
Submission received: 9 September 2024 / Revised: 10 October 2024 / Accepted: 14 October 2024 / Published: 20 October 2024
(This article belongs to the Section Natural Products)
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Abstract

Caffeic acid (CA) is a polyphenolic acid compound widely distributed in plant seeds. As natural compounds with high research interest, caffeic acid and its derivatives show good activity in the treatment of tumors and inflammation and have antibacterial properties. In recent years, caffeic acid derivatives have been studied extensively, and these derivatives fall roughly into three categories: (1) caffeic acid ester derivatives, (2) caffeic acid amide derivatives, (3) caffeic acid hybrids. These caffeic acid analogues exert mainly antibacterial and antioxidant activities. Among the caffeic acid analogues summarized in this paper, compounds 1g and CAP10 have good activity against Candida albicans, and their MIC50 is 32 µg/mL and 13 μM, respectively. In a DPPH assay, compounds 3k, 5a, CS2, Phellinsin A and 8j showed strong antioxidant activity, and their IC50 values are 18.6 μM, 67.85 μM, 40.29 μM, 0.29 ± 0.004 mM, 4774.37 ± 137.20 μM, respectively. Overall, compound CAP10 had the best antibacterial activity and compound 3k had the best antioxidant activity. This paper mainly summarizes and discusses some representative caffeic acid analogs, hoping to provide better drug design strategies for the subsequent development of caffeic acid analogs.

1. Introduction

Caffeic acid (CA), also known as dihydroxycinnamic acid, is a kind of polyphenolic organic acid [1,2,3,4,5,6] (Figure 1). It is widely found in plant seeds, specifically in coffee, vegetables, fruits, olive oil, grains and other Chinese medicinal materials [7,8,9,10,11,12,13]. Vegetables and fruits rich in caffeic acid in nature mainly include spinach, thyme, apples, pears, blueberries and so on. Caffeic acid is also found in many Chinese herbs that are widely used worldwide, such as dandelion, cinnamon, salvia miltiorrhiza, hawthorn, honeysuckle and eucommia ulmoides, as well as plants in the umbrella family and honeysuckle family [2]. In pharmacopoeia, the quantitative analysis of caffeic acid is an important quality control index to ensure that the caffeic acid content in medicinal materials meets the prescribed standards. For example, in the Chinese Pharmacopoeia (2020 edition), the items related to the identification and content determination of dandelion have changed: the caffeic acid content is no longer determined, but is replaced by chicory acid as a reference product. At present, the commonly used methods for caffeic acid quantitative analysis mainly include high performance liquid chromatography and volumetric titration [14,15]. The structural formula for caffeic acid has two phenolic hydroxyl groups [16,17,18]. These two phenolic hydroxyl groups are good donors of hydrogen atoms and are able to react with free radicals, thus neutralizing their activity. This gives caffeic acid the ability to scavenge peroxyl radicals and hydroxyl radicals, hence it exhibits some antioxidant activity [19,20,21]. Meanwhile, in the structure of caffeic acid, the conjugation between the double bond and the benzene ring stabilizes the two phenolic hydroxyl groups as well as the electron transfer process in the reaction of free radicals, which further improves the antioxidant effects [22]. As a natural product with wide application prospects, research on caffeic acid and its homologues has become a hot topic, and some caffeic acid analogues have good antibacterial and antioxidant effects. Therefore, the authors believe that it is necessary to carry out a review of caffeic acid analogues, which can provide better drug design strategies for subsequent caffeic acid analogues research. At the same time, this review is expected to provide some data to support the subsequent development of better caffeic acid analogues [23,24,25,26].

2. Caffeic Acid Derivatives

Caffeic acid derivatives have profound prospects for research due to their high biological activity and wide-ranging biological sources [27,28,29,30]. The synthesis of caffeic acid derivatives has been worked on extensively, and these derivatives fall roughly into three categories: (1) caffeic acid ester derivatives, (2) caffeic acid amide derivatives, (3) caffeic acid hybrids. Caffeic acid ester derivatives mainly include phenethyl caffeate, caffeoylquinic acid, compounds 1g and CAP10. Among them, compounds 1g and CAP10 have good antibacterial activity. Caffeic acid amide derivatives mainly include compounds 3k, 4′d and 5a. Studies have shown that these compounds have a certain antioxidant capacity, and compounds 3k and 5a in particular have a strong antioxidant capacity. In addition, the caffeic acid hybrids reported mainly contain compounds CS2, Phellinsin A and 8j. The DPPH assay indicated that these compounds also have a good antioxidant capacity (Table 1).

2.1. Caffeic Acid Ester Derivatives

Among caffeic acid derivatives, the synthesis and bioactivity of ester derivatives are studied most widely [42,43,44,45,46]. These derivatives are mainly synthesized through a reaction between caffeic acid and different alcohols [47,48,49,50]. Thus, the main differences in the structure of caffeic ester derivatives result from the differences in alcohol. Alcohols used in these reactions include open chain alkyl alcohols, aromatic alcohols and heterocyclic alcohols.
Phenethyl caffeate (CAPE) (Figure 2) is an extensively studied ester derivative [51,52,53,54]. It was found that phenethyl caffeic acid shows a good activity in the treatment of tumors and inflammation and has antibacterial properties [55,56,57,58,59,60,61,62]. It has been confirmed that phenethyl caffeate shows a good inhibitory activity against S. mutans, and its MIC50 is 5.2 ± 0.8 µg/mL [31]. Considering the bioactivities of CAPE, numerous derivatives of CAPE have been developed. But the large-scale preparation of CAPE is a hot and difficult research topic. Synthetic methods for the preparation of CAPE can be categorized as chemical synthesis and biosynthesis. Chemical synthesis methods (Table 2) for CAPE mainly include the direct catalysis method [63,64,65], the halogen-substituted hydrocarbon method [63], the acyl chloride method [66], the witting reaction [67,68], the malonic acid monoester method [69] and the one pot method [70]. Each of these synthesis methods has its own advantages and disadvantages. For example, catalytic esterification has simple reaction conditions but is costly and time consuming; the halogenated hydrocarbons method is mild but costly and cumbersome; the witting reaction conditions are not harsh, and the yield is considerable, but the triphenylphosphine used is expensive, and it is easy to pollute the environment; the one-pot synthesis method has low cost and high yield but requires the use of more toxic piperidine and pyridine.
Two phenolic hydroxyl groups are important groups in CAPE, and SAR studies have shown that substitution of one of the hydroxyl groups can enhance its activity. In particular, substituting the benzene ring with some electron-withdrawing groups can increase the activity [71].
Similar to CAPE, caffeoylquinic acid is a widely studied ester derivative [72,73,74]. Caffeoylquinic acid belongs to organic acids containing phenolic rings, which are widely distributed in nature, such as Chinese herbs, fruits and so on [75,76]. Fruits rich in caffeoylquinic acid in nature mainly include apples and cherries. Among the Chinese herbs widely used around the world, there are also some rich in caffeoylquinic acid, such as honeysuckle, eucommia ulmoides, cocklebur, hawthorn, tuberous root and so on. The quantitative analysis of caffeoyl quinic acid in pharmacopoeia is mainly carried out using high performance liquid chromatography. This method is widely used for the determination of caffeoyl quinic acid compounds with a high accuracy and precision. Specific examples include the HPLC-PDA method for the determination of the caffeoylquinic acid component in Azolla imbricata [77,78]. The results show that the method has a good repeatability and reliability. Studies have shown that caffeoylquinic acid has anti-tumor, antioxidant, anti-inflammatory, cardiovascular protection, neuroprotection and other biological activities [79,80,81,82]. Caffeoylquinic acid is esterified from caffeic acid and quinic acid. This series of compounds mainly consists of monocaffeoylquinicacids (MCQA, Figure 3), dicaffeoylquinicacids (DCQA, Figure 4) and tricaffeoylquinicacids (TCQA, Figure 5) [83]. Caffeoyl quinic acid compounds have great potential for the treatment of some diseases. For example, 3-CQA isolated from honeysuckle has significant antibacterial effects against Staphylococcus aureus and Escherichia coli [84]. Farias-Pereira et al. [85] conducted a screening test on extracts of green coffee beans and 5-CQA through an obesity model and found 5-CQA to be the main weight loss component of coffee beans. In addition, it has been reported that 5-CQA has good inhibitory activity against Stenotrophomonas maltophilia, and its MIC50 is in the range of 8 to 16 µg/mL [33]. Han et al. [86] compared the activities of three kinds of dicaffeinoquinic acid and found that 3, 4-DCQA, 3, 5-DCQA and 4, 5-DCQA all had significant antibacterial effects. In addition, 3, 5-DCQA can promote the mRNA expression of phosphoglycerate kinase 1 in human neuroblastoma cells and increase the level of intracellular ATP, thus exerting neuroprotective effects on neurons [87].
In light of the bioactivities of caffeoylquinic acid, numerous derivatives of caffeoylquinic acid have been developed. These compounds are composed of many isomers and are prone to isomerization. The activity of caffeoylquinic acid is closely related to the absolute configuration [79]. Therefore, the study of optic isomers could be studied in future studies.
De Vita et al. [32] used different alcohols (fatty alcohols, aromatic alcohols) to synthesize different caffeic ester derivatives through an esterification reaction (Figure 6). The study evaluated the effects of these derivatives on the formation and destruction of Candida albicans biofilm, showing that caffeic acid was more active than fluconazole on mature biofilms after esterification. In particular, compounds 1f, 1g and 1i showed higher activity against mature biofilms than fluconazole, and their MIC50 values were 128, 64 and 64 µg/mL, respectively. In addition, the activity of these three compounds on biofilm formation was higher than that of fluconazole.
Lukac et al. [34] synthesized several phosphor derivatives (CAPs) with different carbon chain lengths using caffeic acid as a starting material (Figure 7). Their biological activity evaluation showed that CAPs exhibited significantly stronger cytotoxic activity in comparison to CA. The results of an antimicrobial test confirmed that CAPs have significant activity compared with caffeic acid, and their MIC50 values for Gram-positive bacteria and Candida albicans ranged from 13 μM to 57 μM. These novel compounds appeared to be promising antimicrobial agents for further research.

2.2. Caffeic Acid Amides Derivatives

Caffeic acid amide derivatives, serving as important derivatives of caffeic acid, are widely found in natural plants and have a high biological activity [88]. Caffeic acid amide derivatives can protect endothelial cells from oxidation [89]. These derivatives are mainly synthesized from caffeic acid with different amines, and the amide groups in the structure have high stability. Therefore, in recent years, researchers have conducted more in-depth research on these kinds of derivatives.
Al-Ostoot et al. [90] synthesized a series of caffeic acid derivatives 2a–j via etherification and coupling action (Figure 8), and their anti-inflammatory and analgesic effects were tested. The results showed that most of the caffeic acid derivatives exerted comparable activity to the reference compound celecoxib. Among these derivatives, compounds 2f and 2g have better activity. And the Cyclooxygenase-I (COX-I)/Cyclooxygenase-II (COX-II) activity ratio of 2f and 2g suggested that these two compounds have the same inhibitory effect. The US Environmental Protection Agency has signed off on a rule banning most uses of dichloromethane in an effort to protect public health. Long-term exposure to dichloromethane can cause diseases such as cancer and have adverse effects on the human body and the environment. Dichloromethane was used in the synthesis of the target compound, and it is suggested that the authors avoid using dichloromethane in the subsequent synthesis of such compounds, and use other solvents instead, such as DMF.
Wang et al. [35] synthesized twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES, Figure 9, Table 3) by using amino acids and caffeic acid homologs as the initial material. Their results showed that all CAES have the ability to scavenge free radicals, and N-caffeoyl amide derivatives showed higher radical scavenging activity than N-feruloyl amide derivatives. Among the series of derivatives, compound 3k has the strongest free radical scavenging ability and its IC50 value is 18.6 µM.
Considering the special properties (flexible chain, small steric resistance) of caffeic acid and its homologue, Zhu et al. [36] prepared several derivatives that can be used for the dual inhibition of HIV-1 protease (PR)/reverse transcriptase (RT) (Figure 10, Table 4). These inhibitors were synthesized by reacting substituted cinnamic acids or substituted phenylpropionic acids with corresponding amines in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI)/1-hydroxybenzotriazole (HOBT)/4-dimethylaminopyridine (DMAP) at 0–25 °C for 2–3 h. Among the series of derivatives, the anti-PR activity of compound 4′d was 19 times higher compared with the control DRV, and its IC50 value is 0.081 nM. Compound 4′c exhibited an excellent anti-RT IC50 value of 0.43 µM.
Li et al. [37] synthesized a novel class of proteolytic enzyme β-secretase (BACE1) inhibitors with free radical-scavenging activity (Figure 11). These inhibitors were synthesized via molecular hybridization by using 6-(aminomethyl)pyridin-2-amine and corresponding substituted acids as raw materials under the conditions of EDCI/HOBT. Activity test showed that compound 5a has strong inhibitory and antioxidant activity against BACE1 and DPPH, indicating that compound 5a has good research value for follow-up research.

2.3. Caffeic Acid Hybrids

In recent years, more and more cases have been reported using hybrid strategies to combine caffeic acid with clinical drugs to obtain new molecular entities with good activity. The advantage of these hybrids is that they can simultaneously maintain the pharmacological activity of caffeic acid homologues and clinical drugs, while enhancing synergies [91].
Peng et al. [38] prepared several hybrids (CSs) by linking caffeic acid to sulfonamides using a coupling strategy (Figure 12). These hybrids were evaluated for a series of biological activities and the results indicated that CSs have good effects in a range of antioxidant, anticoagulant and antibacterial activities, present cytotoxicity and promote chondrocyte proliferation.
Gabriele et al. [39] synthesized a set of new sulfurated drug hybrids of cinnamic acids (Figure 13) and tested their inhibition of STAT3 and NF-κB transcription factors. The results showed that most of these compounds can bind to STAT3 selectively. In addition, some drugs can inhibit HCT-116 cell proliferation and NF-κB transcriptional activity, and the corresponding IC50 values are in the micromolar range. These hybrids have great significance for the subsequent development of multi-target anticancer drugs. The use of dichloromethane in the synthesis of the target compound can cause adverse effects on humans and the environment and is not in compliance with the U.S. Environmental Protection Agency’s regulations restricting the use of dichloromethane. It is suggested that the authors should avoid the use of dichloromethane in the subsequent synthesis of similar compounds, and use other solvents instead, such as acetonitrile.
Nemadziva et al. [40] synthesized a dimer compound (Phellinsin A). The results showed that Phellinsin A (Figure 14) had a strong DPPH free radical scavenging ability and equivalent antioxidant capacity (TEAC). Compared to caffeic acid, these two capabilities increased by 1.5 times and 1.8 times, respectively. Furthermore, in aqueous media and an acidic pH, Phellinsin A exhibited improved solubility properties and good stability.
In addition, He et al. [92] prepared several kinds of novel dimers using ferulic acid and CA (Figure 15), then tested the therapeutic effect of these dimers on Alzheimer’s disease (AD). It turned out that compound 7h had a strong protective function on HT22 cells of mice hippocampal neurons, and no obvious cytotoxicity. These data suggest that compound 7h is an important reference for the development of multifunctional drugs in the AD class.
Elkamhawy et al. [41] synthesized some hybrids based on indole groups and caffeic acid homologues (Figure 16). The antioxidant activity of synthesized compounds was evaluated by radical scavenging assays. The DPPH assay demonstrated that these hybrids are more active free radical scavenging agents. In particular, compound 8j presented the highest antioxidant activity with a ferric reducing ability of plasma (FRAP) assay value of 4774.37 ± 137.20 µM Trolox eq/mM sample. Taken together, compound 8j was shown to be optimized to maximize its antioxidant capacity.

3. Conclusions

The design and evaluation of the therapeutic activity of caffeic acid derivatives have attracted more and more attention, and it turns out that some caffeic acid analogues have good antibacterial and antioxidant effects. Among the caffeic acid derivatives summarized in this paper, the caffeic acid ester derivative compound CAP10 has the best antibacterial activity, while the caffeic acid amide derivative compound 3k has the best antioxidant activity. The structure–activity relationship of caffeic acid analogues has been preliminarily understood. Biological activity of these compounds is closely related to the hydroxyl group on the benzene ring. Specifically, with some electron-absorbing substituent groups on the benzene ring, the derivatives have stronger biological activity. Therefore, new caffeic acid derivatives can be designed by changing the substituents on the benzene ring.
Caffeic acid and its derivatives have been applied for treating cardiovascular and cerebrovascular diseases. For example, caffeic acid tablets can be used to treat leukopenia and sodium ferulate can be used to treat atherosclerosis [93,94]. In addition, the exploration of new applications is also becoming a new research hotspot. For instance, caffeic acid analogues can be used as additives for food preservation due to their antioxidant activity. All in all, caffeic acid analogues are natural active substances with good application prospect. However, hurdles remain in this field. For example, further research on targeting caffeic acid and caffeic acid hybrids is needed. It is believed that with the continuous deepening of research, more and more caffeic acid derivatives with better therapeutic effects will be developed.

Author Contributions

Conceptualization, Y.M., S.W. and Z.-Y.J.; methodology, Y.M., S.W. and H.-K.S.; formal analysis, S.W. and Y.W.; investigation, S.W. and H.-K.S.; resources, S.W. and Y.Z.; data curation, S.W. and Y.W.; writing—original draft preparation, S.W., Y.M. and Y.W.; writing—review and editing, S.W. and Y.M.; supervision, Y.M. and L.-J.G. All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by Natural Science Fund for colleges and universities in Jiangsu Province (21KJB350008 and 24KJA350004); Science and Technology Support Program (Social Development) of Taizhou (TN202135).

Acknowledgments

We thank Yao Zhao and Hong-Kai Sha for their special help.

Conflicts of Interest

The authors declare no conflicts of interest.

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Pharmaceuticals 17 01403 g001
Figure 1. Structure of CA.
Figure 1. Structure of CA.
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Figure 2. Structure of CAPE.
Figure 2. Structure of CAPE.
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Figure 3. The structural formulas of MCQA.
Figure 3. The structural formulas of MCQA.
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Figure 4. The structural formulas of DCQA.
Figure 4. The structural formulas of DCQA.
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Figure 5. The structural formulas of TCQA.
Figure 5. The structural formulas of TCQA.
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Figure 6. Structures of caffeic acid ester derivatives.
Figure 6. Structures of caffeic acid ester derivatives.
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Figure 7. Structures of CAPs.
Figure 7. Structures of CAPs.
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Figure 8. Structures of caffeic acid amides derivatives 2a–j.
Figure 8. Structures of caffeic acid amides derivatives 2a–j.
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Figure 9. Synthesis method for CAES.
Figure 9. Synthesis method for CAES.
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Figure 10. The synthesis method for 4a–e and 4′a–e.
Figure 10. The synthesis method for 4a–e and 4′a–e.
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Figure 11. The synthesis method for 5a–g.
Figure 11. The synthesis method for 5a–g.
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Figure 12. The synthesis method for CSs.
Figure 12. The synthesis method for CSs.
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Figure 13. The synthesis method for 6a–i.
Figure 13. The synthesis method for 6a–i.
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Figure 14. The synthesis method for Phellinsin A.
Figure 14. The synthesis method for Phellinsin A.
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Figure 15. The synthesis method for 7a–h.
Figure 15. The synthesis method for 7a–h.
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Figure 16. The chemical structures of 8a–m.
Figure 16. The chemical structures of 8a–m.
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Table 1. List of chemical structures and therapeutic activities of representative caffeic acid derivatives.
Table 1. List of chemical structures and therapeutic activities of representative caffeic acid derivatives.
Types of DerivativesChemical StructuresBiological ActivitiesReferences
CA-ester derivativesCA-phenethyl ester
Pharmaceuticals 17 01403 i001		Showed antibacterial activity
MIC50 5.2 ± 0.8 µg/mL for S. mutans		[31]
Compound 1g
Pharmaceuticals 17 01403 i002		Showed antibacterial activity
MIC50 32 µg/mL for Candida albicans		[32]
5-CQA
Pharmaceuticals 17 01403 i003		Showed antibacterial activity
MIC50 8–16 µg/mL for Stenotrophomonas maltophilia		[33]
Compound CAP10
Pharmaceuticals 17 01403 i004		Showed antibacterial activity
MIC50 13 μM for Candida albicans		[34]
CA-amides derivativesCompound 3k
Pharmaceuticals 17 01403 i005		Showed antioxidant activity
IC50 18.6 μM		[35]
Compound 4′d
Pharmaceuticals 17 01403 i006		Showed antiviral activity
IC50 0.081 nM for HIV-1 protease		[36]
Compound 5a
Pharmaceuticals 17 01403 i007		Showed antioxidant activity
IC50 67.85 μM		[37]
CA-hybridsCompound CS2
Pharmaceuticals 17 01403 i008		Showed antioxidant activity
IC50 40.29 μM		[38]
Compound 6i
Pharmaceuticals 17 01403 i009		Showed antitumor activity
IC50 46.7 μM for HCT-116 cells		[39]
Compound Phellinsin A
Pharmaceuticals 17 01403 i010		Showed antioxidant activity
IC50 0.29 mM		[40]
Compound 8j
Pharmaceuticals 17 01403 i011		Showed antioxidant activity
IC50 4774.37 μM		[41]
Table 2. The chemical synthesis methods for CAPE.
Table 2. The chemical synthesis methods for CAPE.
Synthetic MethodsReagentsSolventReaction TemperatureReferences
Direct Catalysis MethodCaffeic acid, phenethyl alcohol, toluene-p-sulfonic acidBenzeneReflux[64]
Direct Catalysis MethodCaffeic acid, phenethyl alcohol, dicyclohexylcarbodiimide and dimethylaminopyridine THF/CH2Cl2 (1:1)Room temperature[65]
Halogen-Substituted Hydrocarbon MethodCaffeic acid, β-phenyl ethyl bromide, sodium hydroxideHexamethylphosphoramide (HMPA)Room temperature[63]
Acyl Chloride MethodCaffeic acid, phenethyl alcohol, SOCl2, pyridineNitrobenzeneRefluxing temperature[66]
Witting Reaction3,4-Dihydroxy benzaldehyde, triphenylphosphonic acid phenylethanol ester chloride, potassium carbonateCHCl3/dioxane (1:1)Room temperature[67,68]
Malonic Acid Monoester MethodMalonic acid, phenethyl alcohol, DPAT, 3,4-dihydroxy benzaldehydeToluene80 °C[69]
One Pot MethodIsopropylidene malonate, phenethyl alcohol, 3,4-dihydroxy benzaldehyde, pyridine, piperidineToluene60 °C–room temperature [70]
Table 3. The structures of 3a–l.
Table 3. The structures of 3a–l.
CompoundR1R2R3
3aOCH3OHCH3
3bOCH3OHCH(CH3)2
3cOCH3OHCH2CH(CH3)2
3dOCH3OOCCH3CH3
3eOCH3OOCCH3CH(CH3)2
3fOCH3OOCCH3CH2CH(CH3)2
3gOHOHCH3
3hOHOHCH(CH3)2
3iOHOHCH2CH(CH3)2
3jOHOHCH(CH3)CH2CH3
3kOHOHH
3lOHOHCH2C6H6
Table 4. The structures for 4a-e and 4′a–e.
Table 4. The structures for 4a-e and 4′a–e.
CompoundR1R2R3R4R5X
4aCH2CH(CH3)2OCH3OHOHHCH
4bCH2CH(CH3)2NH2OHOHHCH
4cCH2CH(CH3)2SCH3OHOHHCH
4dCH2CH(CH3)2OCH3OHOHHN
4eCH2CH2CH3OCH3OHOHHCH
4′aCH2CH(CH3)2OCH3OHOHHCH
4′bCH2CH(CH3)2NH2OHOHHCH
4′cCH2CH(CH3)2SCH3OHOHHCH
4′dCH2CH(CH3)2OCH3OHOHHN
4′eCH2CH2CH3OCH3OHOHHCH
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Mou, Y.; Wen, S.; Sha, H.-K.; Zhao, Y.; Gui, L.-J.; Wang, Y.; Jiang, Z.-Y. Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents. Pharmaceuticals 2024, 17, 1403. https://doi.org/10.3390/ph17101403

AMA Style

Mou Y, Wen S, Sha H-K, Zhao Y, Gui L-J, Wang Y, Jiang Z-Y. Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents. Pharmaceuticals. 2024; 17(10):1403. https://doi.org/10.3390/ph17101403

Chicago/Turabian Style

Mou, Yi, Shuai Wen, Hong-Kai Sha, Yao Zhao, Li-Juan Gui, Yan Wang, and Zheng-Yu Jiang. 2024. "Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents" Pharmaceuticals 17, no. 10: 1403. https://doi.org/10.3390/ph17101403

APA Style

Mou, Y., Wen, S., Sha, H.-K., Zhao, Y., Gui, L.-J., Wang, Y., & Jiang, Z.-Y. (2024). Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents. Pharmaceuticals, 17(10), 1403. https://doi.org/10.3390/ph17101403

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