Description:FIELD OF THE INVENTION
The present invention relates to methods of synthesizing cashew phenolic lipids. More particularly, the present invention discloses methods for the synthesis of cardol and cardanol, which is rapid and scalable. Said cashew phenolic lipids possesses anti-diabetic activities.

BACKGROUND OF THE INVENTION
Cashew nut shell liquid (CNSL), a byproduct of the cashew industry, is a rich source of phenolic lipids. These compounds have attracted significant interest due to their potential applications in various fields, such as medicine, materials science, and agriculture.

Cardol is another phenolic compound derived from CNSL, characterized by a long alkyl chain with a hydroxyl group. It remains liquid at relatively low temperatures, with a freezing point below 20°C. Cardol exhibits high viscosity and durability. It is majorly used in surface coatings, rubber industry, medical applications and as friction material.

Cardanol is closely related to cardol but has an additional unsaturation in its alkyl chain. This compound also exhibits excellent chemical resistance and low volatility, making it suitable for various applications.

However, the extraction and synthesis of cashew phenolic lipids acid from natural sources have been associated with several challenges.

Reference is made to patent application no. WO2022106988-A1 titled as “method for obtaining a mixture of derivatives of at least two compounds chosen from the cardol, cardanol and anacardic acids”. The prior art relates to a method for obtaining a mixture of oxycarboxylate and/or oxycarboxylic acid derivatives of at least two compounds chosen from the cardols, cardanols and anacardic acids. Characteristically, said one or more families of four compounds are added to a salt of a halogenated carboxylate derivative and/or to a halogenated carboxylic ester in a solution containing a strong base and an alcohol and the resulting reaction mixture is heated to a temperature greater than or equal to 50°C and less than or equal to 90°C and in particular equal to 70°C, for a given period.

Reference was made to a non-patented document titled as “Synthesis of pharmaceutical drugs from cardanol derived from cashew nut shell liquid” by Yiping Shi, Paul C. J. Kamer § and David J. Cole-Hamilton. The paper describes how a cardanol from cashew nut shell liquid extracted from cashew nut shells was successfully converted into various useful pharmaceutical drugs, such as norfenefrine, rac-phenylephrine, etilefrine and fenoprofene. 3-Vinylphenol, the key intermediate for the synthesis of these drugs, was synthesised from cardanol by ethenolysis to 3-non-8-enylphenol followed by isomerising ethenolysis. The metathesis reaction worked very well using DCM, but the greener solvent, 2-methyl tetrahydrofuran, also gave very similar results. Hydroamination of 3-vinylphenol with an iron porphyrin catalyst afforded norfenefrine in over 70% yield. Methylation and ethylation of norfenefrine afforded rac-phenylephrine and etilefrine respectively. A sequence of C–O coupling, isomerising metathesis and selective methoxycarbonylation afforded fenoprofene in good yield.

Another reference is made to patent application no. US7825284B2 titled as “Process for the production of cardanol”. The prior art discloses a process for the production of a color-stable composition containing cardanol and cardol including (a) subjecting crude, cashew nutshell liquid to distillation to obtain a distillate: (b) reacting the distillate with boric acid to obtain a reaction mixture; and (c) subjecting the reaction mixture to distillation is provided. A method for the production of color-stable phenalkamines including (a) subjecting crude, cashew nutshell liquid to distillation to obtain a distillate; (b) reacting the distillate with boric acid to obtain a reaction mixture; (c) subjecting the reaction mixture to distillation to obtain a main fraction; and (d) reacting the main fraction with an aliphatic amine and formaldehyde to form a color-stable phenalkamine is also provided.

Accordingly, prior research has focused on extracting and purifying these compounds directly from CNSL. However, this approach has limitations, including low yields, complex purification processes, and potential environmental concerns. Additionally, the composition of CNSL can vary depending on factors such as geographical origin and processing conditions, making it difficult to obtain consistent and high-quality products

Therefore, to overcome these challenges, a novel synthetic approach is required. This invention aims to provide a more efficient and controlled method for synthesizing cashew phenolic lipids, enabling the production of high-purity compounds with consistent quality. The use of Suzuki-Miyaura coupling, a powerful tool in organic synthesis, allows for the modular assembly of complex molecules, including those found in CNSL.
By developing efficient synthetic routes, this invention contributes to the sustainable utilization of cashew nut shells, reducing waste and promoting the development of value-added products from this renewable resource.

OBJECT OF THE INVENTION
In order to overcome the shortcomings in the existing state of the art, the present invention provides novel methods for synthesizing phenolic lipids, using different synthetic methodologies.

Yet another objective of the invention is to provide different methods for synthesizing phenolic lipids with varying yields.

Yet another objective of the invention is to provide novel methods for synthesizing phenolic lipids, a biologically active compound using different synthetic methods.

Yet another objective of the invention is to provide methods that are efficient, and scalable to multi-gram levels.

Another objective of the present invention is to provide a method for synthesizing phenolic lipids which devoid of the use of hazardous pyrophoric reagents for deprotection, making the synthetic process safer and more environmentally friendly.

Yet another objective of the present invention is to provide a method of synthesizing phenolic lipids which is optimized by reducing the steps of synthesis and requires minimum purification efforts, hence reducing the cost of overall synthesis.

SUMMARY OF THE INVENTION:
The present invention provides innovative methods for synthesizing cashew phenolic lipids with high yields and efficiency, thereby advancing the potential therapeutic applications of these compounds in metabolic and viral disease treatments.

More particularly, the present invention discloses novel methods for synthesizing cardol and cardanol, which is rapid and scalable.

The method involves using a chemical reaction called Suzuki-Miyaura Coupling (SMC) to create important natural compounds like cardol and cardanol. The process starts with method for synthesizing cashew phenolic lipids comprising the steps of reacting a substituted aromatic compound with a suitable alkylating agent in the presence of a base to form an intermediate compound; and reacting the intermediate compound with a nucleophile to form the desired cashew phenolic lipid.
The method wherein the substituted aromatic compound is selected from the group consisting of dimethoxy bromobenzene and methoxy bromobenzene, the alkylating agent is a haloalkane, the base is an organic base and the nucleophile is a phenol.

Another method of synthesizing cashew phenolic lipids by reacting to a substituted aromatic compound with a suitable alkylating agent in a one-pot reaction to form the desired cashew phenolic lipid.

The methods are efficient and produce cardol and cardanol in good yields, making it a valuable tool for chemists.

A protection-free, one-pot synthesis strategy as disclosed above is developed for synthesis of cardol and cardanol, further improving efficiency and yield to 70-75%.

Hence, SMC reaction is successful in making natural products such as cardol and cardanol with good overall yield.

BRIEF DESCRIPTION OF DRAWINGS
Scheme 1 depicts Synthesis of cardol and cardanol.

DETAILED DESCRIPTION OF THE INVENTION WITH ILLUSTRATIONS AND EXAMPLES
While the invention has been disclosed with reference to certain embodiments, it will be understood by those skilled in the art that various changes may be made, and equivalents may be substituted without departing from the scope of the invention. In addition, many modifications may be made to adapt to a particular situation or material to the teachings of the invention without departing from its scope.

Throughout the specification and claims, the following terms take the meanings explicitly associated herein unless the context clearly dictates otherwise. The meaning of “a”, “an”, and “the” include plural references. Additionally, a reference to the singular includes a reference to the plural unless otherwise stated or inconsistent with the disclosure herein.

This invention presents innovative methods for synthesizing cashew phenolic lipids, a compound with potential applications in treating metabolic and viral diseases. The whole route is novel and a shortened path for synthesizing cashew phenolic lipids such as cardol and cardanol as shown in scheme 1, which are constituents of the Anacardium occidentale plant has been synthesized very efficiently.

Scheme 1: Synthesis of cardol and cardanol.

Cardol and Cardanol
Cardol and Cardanol are also synthesized from dimethoxy bromobenzene/methoxy bromobenzene under the same conditions. The overall yield of the cardol and cardanol is about 80-82%. This is one of the highest yields obtained compared to the other known methods reported in the literature. Further, another strategy-protection-free method with one pot reaction is developed for the synthesis of cardol and cardanol as shown in scheme 1. For the synthesis of cardol and cardanol without the protection of hydroxyl groups and obtained with the overall yield ranging from 70-75%.

Hence, SMC reaction is successful in making natural products such as cardol, and cardanol with good overall yield.

Accordingly, the present invention offers a streamlined and effective route to produce valuable cashew phenolic lipids. The improved yields and reduced reaction steps make this method economically attractive and environmentally friendly. By enabling the large-scale production of these compounds, this invention has the potential to accelerate research into their therapeutic applications and contribute to the development of new treatments for metabolic and viral diseases.
, Claims:We claim:
1. A method for synthesizing cardol and cardanol comprising the steps of:
a) reacting a substituted aromatic compound with a suitable alkylating agent in the presence of a base to form an intermediate compound; and
b) reacting the intermediate compound with a nucleophile to form the desired cashew phenolic lipid.
3. The method as claimed in claim 1, wherein the substituted aromatic compound is selected from the group consisting of dimethoxy bromobenzene and methoxy bromobenzene.
4. The method as claimed in claim 1, wherein the alkylating agent is a haloalkane.
5. The method as claimed in claim 1, wherein the base is an organic base.
6. The method as claimed in claim 1, wherein the nucleophile is a phenol.
7. The method as claimed in claim 1, wherein the cashew phenolic lipid is selected from the group consisting of cardol and cardanol.
8. A method for synthesizing cardol and cardanol by reacting to a substituted aromatic compound with a suitable alkylating agent in a one-pot reaction to form the desired cashew phenolic lipid.