Amide is the organic compound which contains the acyl map group connected to nitrogen atom from the C atom the individual bond which links the carbonyl atom with nitrogen atom is called an amide linkage. ( Specer et al, 2004 ) .
The general of amide is ( R-CONH2 ) which is considered one derived function of ammonium hydroxide that is one H atom has been replaced by acyl group, amides can be derived from primary aminoalkanes ( R-NH2 ) to give a primary amides and from secondary aminoalkanes to give a secondary amides, besides amides are regarded as derived functions of carboxylic acids in which the hydroxyl group has replaced by aminoalkane. ( Specer et al, 2004 ) .
1.3. Physical belongingss:
At the room temperature, all the amides are solids expect formamide because it is unsubstituted amide, unsubstituted amides can organize a web of intermolecular H bonds and this character makes runing points for these substances so high. However, the permutation of alkyl or aromatic group on N reduces the figure of inter molecular H bond, accordingly the thaw point will diminish, so disubstituted amide frequently have lower thaw and boiling points than monosubstituted and unsubstituted amides. Amides are instead H2O soluble particularly which contains less than six Cs and this is due to ability of amides to organize H bond with H2O even disubstituted amides can make this because of the presence of carbonyl O. . ( Specer et al, 2004 ) .
Fig. 2: The intermolecular H bonds of amides
1.4. Chemical belongingss:
Amides are neither basic nor acidic, they are impersonal because the carbonyl group bonded to the N has decreased the basicity of the original aminoalkane
1.4.2. Amide hydrolysis:
Amide hydrolysis is the reaction between amide and H2O in the presence of acid or base with heat to bring forth carboxylic acid and aminoalkane. In fact, amide hydrolysis is really of import reaction in biochemistry because it is a halfway reaction in the digestion of proteins and the dislocation of proteins with cells. ( Specer et al, 2004 ) .
Amides are permeant in nature and engineering as structural stuffs. The best known of all man-made amides is the fibre known as nylon. In 1931, the American chemist Wallace Hume Carothers discovered a procedure for doing one of the first man-made fibres. He found that the add-on of adipic acid to hexamethylene diamine resulted in the formation of a strong, fiber-like merchandise to which he gave the name Nylon 66. The 66 portion of the name reflects the fact that adipic acid and hexamethylene diamine each contain six C atoms in their molecules. The reaction between these two substances consequences in the formation of a long polymer, slightly similar to the construction of natural protein. As in protein, the fractional monetary units of nylon are joined by amide bonds. For this ground, both protein and nylon can be thought of as polymeric amides, compounds in which a big figure of amide units are joined to each other in a long concatenation. Other types of nylon were besides developed at subsequently day of the months. One signifier, known as Nylon 6, is produced by the polymerisation of a individual sort of molecule, 6-aminohexanoic acid. The bonding between sub-units in Nylon-6-amide bonds is the same as it is in Nylon 66. In all types of nylon, the fibre obtains its strength from H bonding that occurs between O and H atoms on next ironss of the stuff. Another type of polymer is formed when two of the simplest organic compounds, urea and formaldehyde, react with each other. In this reaction, amide bonds form between alternate carbamides and formaldehyde molecules, ensuing in a really long polymeric amide concatenation. Urea formaldehyde polymers are in great demand by industry, where they are used as modeling compounds, in the intervention of paper and fabrics, and as a binder in atom board, to advert but a few utilizations.
( Raymond Seymour et Al, 1986 )
18.104.22.168. General drugs:
Amides have physiological belongingss, a figure of amides play valuable regulations in medical specialty, for illustration the amide Datril marked under name of Tylenol which is considered as amide and used as hurting stand-in represented in fig 2
Fig. 2: Acetaminophen
Table 1 below shows a few of import amides and their utilizations.
Table.1: Some of import amides in medical specialty ( Specer et al, 2004 ) .
( Pentothal )
( Amytal )
Treatment of Insomnia
( Valim )
( Polycillin )
22.214.171.124. Anticancer drugs:
One of the most of import applications of amides as anticancer agent for many malignant neoplastic disease types, for illustration, the amide alkolides ( 1-3 ) are evaluated for their anticancer activity againist colon ( HT-29 ( , chest ( MCF-7 ) and lung ( A549 ) human malignant neoplastic disease cell lines ( Srinivas et al,2009 ) .
Fig. 3: Examples of the amide alkolides
Furthermore, N-substituted amides of 3- ( 3-ethylthio-1, 2, 4-triazole-S-yl ) propenoic acid were found to be biologically active and effectual in vitro against lung cell line. ( Anna Pachuta et Al, 2009 ) .
1- 2- 3- 4-
Fig. 4: Examples of the amide 3- ( 3-ethylthio-1, 2, 4-triazole-S-yl ) propenoic acid
Amides are normally formed via reactions of a carboxylic acid with an aminoalkane. Many methods are known for driving the unfavourable equilibrium to the right:
RCO2H + R’R ” NH RC ( O ) NR’R ” + H2O
For the most portion, these reactions involve “ triping ” the carboxylic acid and the best known method, the Schotten-Baumann reaction, which involves transition of the acid to the acid chlorides: ( Michael B. Smith et Al, 2001 )
Table.2: Some of import reactions for synthesis of amides
Reaction nameA A
reagent: hydroxylamineand acid
reagent: hydrazoic acid
reagent: H2O ; acid accelerator
aryl alkyl ketones
S and morpholine
carboxylic acid, ketone or aldehyde
isocyanide, carboxylic acid, ketone, primary aminoalkane
carboxylic acid, Grignard reagentwith an anilinederivative ArNHR ‘
A lipase is a H2O soluble enzyme of considerable physiological significance and industrial potency belongingss which catalyzes the hydrolysis and synthesis of ester bonds formed from glycerin and long concatenation of fatty acids. ( Monica Fernandez and Cristina Otero, 2001 ) .
lipases are involved in many phases of lipid metamorphosis including fat digestion, reconstitution, soaking up and lipoprotein metamorphosis, many lipases are really active in organic dissolvers, they catalyze a figure of a utile reactions such as: esterification, transesterification, regioselective acylation of ethanediol and synthesis of peptides, commercially utile lipases are normally obtained from micro-organisms. ( Rohit Sharma et Al, 2001 )
Lipases occur widely in nature, but merely microbic lipases are commercially important, lipases have many applications including organic synthesis, hydrolysis of fats and oils, declaration of racemic mixture, detergents, nutrient processing, synthesis of all right chemicals, production of cosmetics and pharmaceutical chemical science, major applications of lipases are summarized in table.3 ( Rohit Sharma et Al, 2001 )
Table.3: Industrial applications of Microbial lipases
Industry Action Product or application
Detergents Hydrolysis of fats Removal of oil discolorations from cloths
Dairy nutrients Hydrolysis of milk fat Development of seasoning agents in milk
Bakery nutrients Flavor betterment Shelf-life protraction
Beverages Improved olfactory property Beverages
Food dressings Quality betterment Mayonnaise, dressings, and tannings
Health nutrients Transesterification Health nutrients
Meat and fish Flavor development Meat and fish merchandises ; fat remotion
Fats and oils Transesterification ; hydrolysis Cocoa butter, oleo, fatty acids
Chemicals Enantioselectivity, synthesis Chiral edifice blocks, chemicals
Pharmaceuticals Transesterification, hydrolysis Specialty lipoids, digestive AIDSs
Cosmetics Synthesis Emulsifiers, moisturizers
Leather Hydrolysis Leather merchandises
Paper Hydrolysis Paper with improved quality
Cleaning Hydrolysis Removal of fats
Natural merchandises which contain amide group are biologically interesting molecules and play an of import function in modern drug find, particularly in malignant neoplastic disease intervention ( ch srinivas et Al, 2009 ) .
There are many workss in the universe contain so of import natural merchandises which have cytotoxic activity a against human malignant neoplastic disease cells. One of the most of import workss is Litsea ( L. auraceae ) which comprises about 200 species, which are widely found in tropical and semitropical Asia, North America, and semitropical South America. The Litsea workss have been reported to hold a important cytotoxic activity against human tumour cells, including human chest glandular cancer, non-small-cell lung malignant neoplastic disease, and spongioblastoma cell lines. ( Hitoshi Tanaka et Al, 2009 ) .
Hitoshi Tanaka described the isolation and structural elucidation of a new amide, N-trans-sinapoylmethoxytyr aminoalkane figure ( 1 ) , along with three known amides ( 2-4 ) .
Figer.5: The four amides extracted from litsea
After doing full reappraisal for the literatures, it was concluded that compound ( 1 ) has ne’er been synthesized and there is no any suggested method for its synthesis, compound ( 2 ) has merely one method for synthesis ( Jae Park et Al, 2003 ) , with a low output ( 55.0 ) % , compound ( 3 ) has been prepared by ( Hitoshi Tanaka et Al, 1989 ) , besides with a low output ( 55.0 ) % , compound ( 4 ) was prepared by responding amino ethyl phenol with chloro carbonyl vinyl methoxy ester, ( Esaku Nomura et al,2003 ) , although this method gave good output ( 94.0 ) % but it needs hydrazine as a reagent which considered unsafe chemical. Besides ( Jae Park et Al, 2003 ) have synthesized compound ( 4 ) with a low output ( 55.0 ) % .
In add-on to them, Yoshimitsu have synthesized compound ( 4 ) was synthesized by the yoke of ferulic acid with tyramine in t-BuOH utilizing ( DCC ) ( Yoshimitsu Yamazaki et Al, 2008 ) .
Nowadays, many accelerators used to synthesise amides, but biocatalysts enzymes such as lipases accelerators are considered the best accelerators because of its high stableness in organic media and their ability to accept a great assortment of substrates ( Monica Fernandez and Cristina Otero, 2001 ) .
Problem of the research
Litsea workss are considered a major beginning for natural merchandises which have a important cytotoxtic activity against human tumour cells, hence four amides ( 1 ) , ( 2 ) , ( 3 ) and ( 4 ) which are constituents of litsea workss are so valuable and of import compounds to be studied.
A new amide N-trans-sinapoylmethoxytyr aminoalkane ( 1 ) which was discovered by ( Hitoshi Tanaka et Al, 2009 ) , who has isolated compound ( 1 ) from the foliages and branchlets of L. auriculata. However, there is no any suggested method for the synthesis of compound N-trans-sinapoylmethoxytyr aminoalkane compound ( 1 ) , compound ( 2 ) has merely one method for synthesis ( Jae Park et Al, 2003 ) , with a low output ( 55.0 ) % , compound ( 3 ) has been prepared by ( Hitoshi Tanaka et Al, 1989 ) , besides with a low output ( 55.0 ) % , compound ( 4 ) was prepared by ( Esaku Nomura et al,2003 ) , although this method gave good output ( 94.0 ) % but it needs hydrazine as a reagent which considered as a unsafe chemical. Besides ( Jae Park et Al, 2003 ) have synthesized compound ( 4 ) with a low output ( 55.0 ) % . In add-on to them, ( Yoshimitsu Yamazaki et Al, 2008 ) have synthesized compound ( 4 ) was synthesized by the yoke of ferulic acid with tyramine in t-BuOH utilizing ( DCC ) .
The output of the extraction method from the works is excessively hapless ( each 10 kilogram of the works is required to pull out merely 60 milligram of the compound ( 1 ) , 133 milligram of compound ( 2 ) , 28.9 milligram of compound ( 3 ) and 47 milligram of compound ( 4 ) . Therefore, it is of import to happen a new direct method to synthesis compounds ( 1 ) , ( 2 ) , ( 3 ) and ( 4 ) .
The first end of this research is to synthesise the amides, N-trans-sinapoylmethoxytyr aminoalkane compound ( 1 ) , N-trans-sinapoyltyr aminoalkane compound ( 2 ) , N-trans-feruloylmethoxytyr aminoalkane compound ( 3 ) and N-trans-feruloyltyr aminoalkane compound ( 4 ) .
To optimise the best synthesis conditions for each compound.
Statistical ( ANOVA ) trial and ( RSM ) analysis for the informations will be calculated.
To analyze dynamicss of the reactions for each compound.
To analyze the anticancer activity for each compound.
Compound ( 1 ) N-trans-sinapoylmethoxytyr aminoalkane will be synthesized by responding ( 3, 5-Dimethoxy-4-hydroxycinnamic acid ) with ( 3-O-Methyldopamine hydrochloride ) in the presence of Lipase accelerator.
Compound ( 2 ) N-trans-sinapoyltyr aminoalkane will be synthesized by responding responding ( 3, 5-Dimethoxy-4-hydroxycinnamic acid ) with ( Tyramine hydrochloride ) in the presence of Lipase accelerator.
Compound ( 3 ) N-trans-feruloylmethoxytyr aminoalkane will be synthesized by responding responding ( 4-Hydroxy-3-methoxycinnamic acid ) with ( 3-O-Methyldopamine hydrochloride ) in the presence of Lipase accelerator.
Compound ( 4 ) N-trans-feruloyltyr aminoalkane will be synthesized responding ( 4-Hydroxy-3-methoxycinnamic acid ) with ( Tyramine hydrochloride ) in the presence of Lipase accelerator.
The equation below represents the strategy of synthesis:
Designation of the new compounds utilizing IR, NMR and prove the pureness of it utilizing HPLC.
Analyzing the cytotoxic activity and bioactivity of the four amide compounds against malignant neoplastic disease.
Optimize the best conditions for the reaction by analyzing:
Consequence of clip on the reaction
Consequence of temperature on the reaction
Consequence of the organic dissolver on the reaction
Consequence of molar ratio on the reaction
Consequence of lipase sum on the reaction
Four amides will be prepared utilizing direct synthesis in presence of lipase accelerator, N-trans-sinapoylmethoxytyr aminoalkane compound ( 1 ) which is new amide, N-trans-sinapoyltyr aminoalkane compound ( 2 ) , N-trans-feruloylmethoxytyr aminoalkane compound ( 3 ) and N-trans-feruloyltyr aminoalkane compound ( 4 ) .
The output of the merchandises for the synthesis method expected to be good.
One amide at least expected to be bioactive against malignant neoplastic disease cells.