Abstract:
The present invention is directed towards the synthesis of novel and new chloropyridine skeleton based compounds and these are Bayllis Hillman adducts having a remarkable in vitro anti-malarial activity. These compounds have been found to possess anti-malarial activity against chloroquine sensitive and chloroquine resistant  Plasmodium falciparum . The anti-malarial compounds of the present invention inhibit the mature schizonts in vitro.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of International Application No. PCT/IN05/00397, filed Dec. 2, 2005, and Indian Patent Application No. 2462/DEL/2005, filed Nov. 22, 2005, the entire contents of each of which being hereby incorporated by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relate to a novel Bayllis Hillman adduct which are having a remarkable in vitro anti-malarial activity against chloroquine sensitive and chloroquine resistance  Plasmodium falciparum  and a process for the preparation thereof. 
     BACKGROUND OF THE INVENTION 
     Malaria is one of the world&#39;s leading killer infectious diseases. Although almost a third of the Earth&#39;s population is considered to be at risk from this disease, about 90% of infections and deaths occur in Africa (Trigg, P. I., and Wernsdorfer, W. H., Parasitologia: (1999) 41, 329-332), contributing significantly to underdevelopment and poverty on this continent (Gallup, J. L., and Sachs, J. D., Am. J. Trop. Med. Hyg: (2001) 64s, 85-96). The estimated 300 million cases that occur per year result in considerable morbidity (e. g. fever, malaise, anorexia, anemia) and mortality of over 2 million children under age group of five (World malaria situation in 1994 part I. Wkly Epidemiol rec: (1997) 72, 269-274. The intracellular protozoal parasite  Plasmodium falciparum , accounts for greater than 95% of the malarial deaths. An important contributor to the increase in incidence of malaria over the past 30 years has been the development of resistance of the malarial parasite to quinoline containing antimalarials such as chloroquine and quinine (Barat, L. M., and Boland, P. B., Drug resistance among malaria and other parasites. Infet Dis Clin North Am: (1997) 11 (4), 969-987). In addition, it has been recognized that a number of complications, such as anemia, failure to gain weight and immunosuppression associated with malaria infection continue to occur for weeks and over months after the parasites are cleared from the body (Ho, M., Webster, H. K., and Looareesuwan, S. Antigen-specific immunosuppression in human malaria due to  plasmodium falciparum . J. Infect Dis: (1986) 153, 763-771; McGregor, A., and Barr, M. Antibody response to tetanus toxoid inoculation in malarious and non-malarious Gambian children. Trans R Soc Trop Med hyg: (1962) 56, 364-367; Bradley-Moore, A. M., Greenwood, B. M. and Bradley, A. K. Malaria chemoprophylaxis with chloroquine in young Nigerian children. II. Effect on immune response to vaccination. Ann Trop Med Parasitol: (1985) 79, 563-573). For the majority of their life-cycle in humans, malaria parasites live in red blood cells. Within the erythrocytes, the parasites feed on hemoglobin, digesting the protein and releasing the heme. The heme which is released as the by-product of hemoglobin is toxic compound to the parasite. The malarial parasite having a unique heme detoxication mechanism that the heme is converted to non-toxic heme polymer hemozoin (malaria pigment) within the food vacuole (Rudzinska, M. A., Trager, W. and Bray, R. S. Pinocytic uptake and the digestion of hemoglobin in malaria parasites. J. Protozool: (1965) 12(4), 563-576). Trager, W; Jensen, J. B. Science, (1976), 193, 674) that serves to protect the parasite from potentially toxic free heme, as well as to induce pathology in the infected host. Overtime, the intraerythrocytic parasite exhausts this energy and protein supply and then begins next stage of life cycle. Through a series of DNA and membrane divisions, trophozoites converted to mature schizonts. Schizonts-containing erythrocytes rupture, each releasing 6 to 24 merozoites and one large ‘garbage bag’ containing polymerized hemozoin. It is this process that produces febrile clinical attack. The released merozoites invade more erythrocytes to continue the cycle, which proceeds until death of the host or modulation by drugs or acquired immunity. The 2-chloropyridine based Baylis Hillman adducts and 4-quinolino-methanols are reported to be antimalarial agents. These classes of compounds are particularly acting on erythrocytic stage of the parasite. 
     The following references are examples for the synthesis of and biological evaluation of some of the antimalarial agents. These prior arts contain useful information and discussion on the preparation and properties of antimalarial agents. 
     U.S. Pat. No. 6,627,641 (2003) reported the synthesis and use of naphthylisoquinoline alkaloids and their pharmaceutical formulation as efficient antmalarial agents. 
     U.S. Pat. No. 6,479,660 (2000) reported the synthesis and use of quinoline compounds as antimalarial drugs. 
     Sujatha, V. B. et. al.  Bioorg  &amp;  Med. Chem. Lett,  9, 731-736 (1999) reported the antimalarial activity of 3-hydroxy alkyl-2-methylene-propionic acid derivatives. 
     U.S. Pat. No. 6,689,777 (2004) reported the synthesis of novel substituted naphthothiozolium, aromatic guanylhydrazones and other compounds and compositions having antimalarial activity. 
     Donald J. Krogstad. et al.,  Science,  238, 1283-1285 (1987) reported the mechanism of chloroquine resistance in plasmodium. 
     U.S. Pat. No. 6,693,217 (2004) reported the synthesis of N, N1-substituted asymmetrical imidodicarbonimidic diamides as antimalarial agents. 
     Arnulf Dorn et al.,  Nature  374, 269-371 (1995) reported the process of heme polymerization and mechanism of action of chloroquine. 
     U.S. Pat. No. 2004/0180913 (2004) reported the synthesis of 2,4-diaminopyrimidine derivatives and their use as antimalarial agents by inhibiting dihydrofolate reductase (DHFR-Inhibitors) 
     Christian Segheraert. et al.  J. Med. Chem.  46, 542-547 (2003) reported the synthesis and antimalarial activity of N 1 -(7-chloro-4quinolyl)-1,4bis(3-aminopropyl) piperazine derivatives. 
     OBJECTS OF THE INVENTION 
     One object of the present invention is to provide novel Baylis Hillman adducts based on the chloropyridine skeleton as anti malarial agents. 
     Another object of the present invention is to provide pharmaceutical composition comprising novel Baylis Hillman adducts as antimalarial agents. 
     Still another object of the present invention is to provide a process for the preparation of novel Baylis Hillman adduct based on the chloropyridine skeleton, as anti malarial agent. 
     SUMMARY OF THE INVENTION 
     The present invention is directed towards the synthesis of novel chloropyridine skeleton based compounds and these are Bayllis Hillman adducts having a remarkable in vitro anti-malarial activity. These compounds have been found to possess anti-malarial activity against chloroquine sensitive and chloroquine resistance  Plasmodium falciparum . The anti-malarial compounds of the present invention inhibit the mature schizonts in vitro. 
     This invention meets the need for more efficient compounds against malaria, in particularly chloroquine resistance  plasmodium falciparum . Accordingly present invention provides novel compounds based on chloropyridine skeleton of general structural formula 1. These are the Baylis Hillman reaction adducts having the general structure of formula I &amp; II indicates total thirty seven (37) compounds which is represented below. 
                                
Ia: R1=H, R2=CH3, X=acrylonitrile; IIa: R1=H, R2=CH3, X=2-cyclopenten-1-one
 
Ib: R1=H, R2=C2H5, X=acrylonitrile IIb: R1=H, R2=C2H5, X=2-cyclopenten-1-one
 
Ic: R1=H, R2=Ph, X=acrylonitrile IIc: R1=H, R2=Ph, X=2-cyclopenten-1-one
 
Id: R1=COOMe, R2=H, X=acrylonitrile IId: R1=Ph, R2=CH3, X=2-cyclopenten-1-one
 
Ie: R1=H, R2=CH3, X=methyl acrylate IIe: R1=COOMe, R2=H, X=2-cyclopenten-1-one
 
If: R1=H, R2=Ph, X=methyl acrylate IIf: R1=Ph, R2=COOEt, X=2-cyclopenten-1-one
 
Ig: R1=H, R2=n-C5H11, X=acrylonitrile IIg: R1=H, R2=4-OMe-Ph, X=2-cyclopenten-1-one
 
Ih: R1=Ph, R2=CH3, X=acrylonitrile IIh: R1=H, R2=CH3, X=2-cyclohexen-1-one
 
Ii: R1=Ph, R2=COOEt, X=acrylonitrile IIi: R1=H, R2=C2H5, X=2-cyclohexen-1-one
 
Ij: R1=H, R2=4-OMe-Ph, X=acrylonitrile IIj: R1=H, R2=Ph, X=2-cyclohexen-1-one
 
Ik: R1=H, R2=C2H5, X=methylacrylate IIk: R1=Ph, R2=CH3, X=2-cyclohexen-1-one
 
Il: R1=H, R2=n-C5H11, X=methylacrylate IIl: R1=COOMe, R2=H, X=2-cyclohexen-1-one
 
Im: R1=Ph, R2=CH3, X=methylacrylate IIm: R1=Ph, R2=COOEt, X=2-cyclohexen-1-one
 
In: R1=COOMe, R2=H, X=methylacrylate IIn: R1=H, R2=4-OMe-Ph, X=cyclohexen-1-one
 
Io: R1=Ph, R2=COOEt, X=methylacrylate
 
Ip: R1=H, R2=4-OMe-Ph, X=methylacrylate
 
Iq: R1=H, R2=CH3, X=ethylacrylate
 
Ir: R1=H, R2=C2H5, X=ethylacrylate
 
Is: R1=H, R2=Ph, X=ethylacrylate
 
It: R1=Ph, R2=CH3, X=ethylacrylate
 
Iu: R1=COOMe, R2=H, X=ethylacrylate
 
Iv: R1=Ph, R2=COOEt, X=ethylacrylate
 
Iw: R1=H, R2=4-OMe-Ph, X=ethylacrylate
 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Accordingly the present invention provides a novel chloro pyridine skelton based Baylis-Hillman adduct having the general formula 
                                
wherein
 
     
       
                 
         
             
             
         
      
     
     R1 is selected from the group consisting of hydrogen, phenyl and carbomethoxy; R2 is selected from the group consisting of hydrogen, alkyl, CH 3 , C 2 H 5 , phenyl, n-C 5 H 11 , carboethoxy and p-OMe-Ph; EWG is an electron withdrawing group selected from the group consisting of CN, COOMe and COOEt. 
     In an embodiment of the present invention the novel chloro pyridine skelton based Baylis-Hillman adduct used comprising the compounds of general formula I &amp; II 
     
       
                 
         
             
             
         
      
     
     R1 is selected from the group consisting of hydrogen, phenyl and carbomethoxy; R2 is selected from the group consisting of hydrogen, alkyl, CH 3 , C 2 H 5 , phenyl, n-C 5 H 11 , carboethoxy and p-OMe-Ph; EWG is an electron withdrawing group selected from the group consisting of CN, COOMe and COOEt. 
     In yet another embodiment the novel chloro pyridine skelton based Baylis-Hillman adduct obtained is in the form of derivatives, analogues or salt thereof. 
     In yet another embodiment the novel chloro pyridine skelton based Baylis-Hillman adduct obtained is selected from the group consisting of 2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ia), 2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ib), 2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ic), methyl 6-chloro-5-(2-cyano-1-hydroxy allyl)2-pyridine carboxylate (Id), Methyl 2-[(2-chloro-5-methylpyridine-3-)(hydroxy)methyl]acrylate (Ie), Methyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (If), 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ig), 2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrle (Ih), Ethyl 6-chloro-5-(2-cyano-1-hydroxy allyl)-2-phenyl-nicotinate (Ii), 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ij), Methyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ik), Methyl 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylate (Il), Methyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Im), Methyl 6-chloro-5-[1-hydroxy-2-(methoxycarbonyl)allyl]pyridine-2-carboxylate (In), Ethyl 6-chloro-5-(1-hydroxy-2-(methoxycarbonyl)allyl)-2-phenyl-nicotinate (Io), Methyl 2-[(2-chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Ip), Ethyl 2-[(2-chloro-5-methylpyridine-3-)(hydroxy)methyl]acrylate (Iq), Ethyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ir), Ethyl 2-[(2-chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Is), Ethyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (It), Methy-6-chloro-5-[1-hydroxy-2-(ethoxycarbonyl)allyl]pyridine-2-carboxylate (Iu), Ethyl 6-chloro-5-(1-hydroxy-2-(ethoxycarbonyl)allyl)-2-phenyl-nicotinate (Iv), Ethyl 2-[(2-chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Iw), 2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIa), 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIb), 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIc), 2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IId), Methyl-6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-pyridine carboxylate (IIe), Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-phenyl nicotinate (IIf), 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIg), 2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]2-cyclohexene1-one (IIh), 2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIi), 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIj), Methyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ik), Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-pyridine carboxylate (IIl), Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-phenyl nicotinate (IIm) and 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one (IIn). 
     In yet another embodiment the novel chloro pyridine skelton based Baylis-Hillman adduct is active against chloroquine sensitive and chloroquine resistant  plasmodium falciparum  strains. 
     In yet another embodiment novel chloro pyridine skelton based Baylis-Hillman adduct exhibits an anti malarial activity against the erythrocytic stage of the malarial parasite. 
     The present invention further provides a pharmaceutical composition comprising novel anti malarial chloro pyridine skelton based Baylis-Hillman adduct, its derivatives, analogues or salt thereof optionally with pharmaceutically acceptable carriers, adjuvant and additives. 
     The present invention further provides a method for the treatment of malaria in a subject wherein a dose of 1-45 μg/ml and 1-115 μg/ml drug is administered for IC50 against chloroquine sensitive (CQS)  P. falciparum  strain to such subject for schizont maturation inhibition (SMI) and total parasite growth inhibition (PGI), for at least 24 and 48 hrs, respectively. 
     In yet another embodiment a dose of 25-125 μg/ml and 85-350 μg/ml drug is administered for IC90 against chloroquine sensitive (CQS)  P. falciparum  strain to such subject for schizont maturation inhibition (SMI) and total parasite growth inhibition (PGI), for at least 24 and 48 hrs, respectively. 
     In yet another embodiment a dose of 0.2-30 μg/ml and 5-15 μg/ml drug is administered for IC50 against chloroquine resistant  plasmodium falciparum  strain to such subject for schizont maturation inhibition (SMI) and total parasite growth inhibition (PGI), for at least 24 and 48 hrs, respectively. 
     In yet another embodiment a dose of 1-125 μg/ml and 25-300 μg/ml drug is administered for IC90 against chloroquine resistant  plasmodium falciparum  strain to such subject for schizont maturation inhibition (SMI) and total parasite growth inhibition (PGI), for at least 24 and 48 hrs, respectively. 
     The present invention further provides a process for the preparation of chloro pyridine skelton based Baylis-Hillman adduct having the general formula 
                                
wherein
 
     
       
                 
         
             
             
         
      
     
     R1 is selected from the group consisting of hydrogen, phenyl and carbomethoxy; R2 is selected from the group consisting of hydrogen, alkyl, CH 3 , C 2 H 5 , phenyl, n-C 5 H 11 , carboethoxy and p-OMe-Ph; EWG is an electron withdrawing group selected from the group consisting of CN, COOMe and COOEt, which comprises reacting 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde with an activated alkene or cyclic enone, optiomally in the presence of aqueous or non aqueous organic solvent, in the presence of a catalyst, at a temperature in the range of 20-30° C., washing the organic layer of the above said reaction mixture with water or brine solution, followed by drying and purification by known method to obtain the desired product. 
     In yet another embodiment the 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde used is selected from the group consisting of 2-Chloro-5-methylpyridinecarboxaldehyde, 2-Chloro-5-ethylnicotinaldehyde, 2-Chloro-5-phenyl nicotinaldehyde, methyl6-chloro-5-formyl-2-pyridincarboxylate, 2-chloro-5-methyl nicotinaldehyde, 2-Chloro-5-phenylnicotinaldehyde, 2-chloro-5-pentylnicotinaldehyde, 2-Chloro-5-methyl-6-phenylnicotinaldehyde, 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde, 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde, 2-Chloro-5-ethylnicotinaldehyde, 2-Chloro-5-pentylnicotinaldehyde, 2-Chloro-5-methyl-6-phenylnicotin aldehyde, Methyl 6-chloro-5-formyl-2-pyridin carboxylate, 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde, 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde, 2-Chloro-5-methyl nicotinaldehyde, 2-Chloro-5-ethylnicotinaldehyde, 2-Chloro-5-phenylnicotin aldehyde, 2-Chloro-5-methyl-6-phenylnicotinaldehyde, Methyl 6-chloro-5-formyl-2-pyridincarboxylate, 2-Chloro-5-ethoxyacetate)-6-phenylnicotin aldehyde, 2-Chloro-5-(4-methoxyphenyl)nicotinaldehyde, 2-Chloro-5-methyl nicotinaldehyde, 2-Chloro-5-ethylnicotin aldehyde, 2-Chloro-5-phenylnicotinaldehyde, 2-Chloro-5-methyl-6-phenylnicotin aldehyde, Methyl 6-chloro-5-formyl-2-pyridincarboxylate, 2-Chloro-5-ethoxyacetate)-6-phenyl nicotinaldehyde, 2-Chloro-5-(4-methoxyphenyl)-nicotin aldehyde, 2-Chloro-5-methylnicotinaldehyde, 2-Chloro-5-ethylnicotinaldehyde, 2-Chloro-5-phenylnicotinaldehyde, 2-chloro-substituted-3-pyridinecarboxy aldehyde, methyl 6-chloro-5-formyl-2-pyridincarboxylate, 2-Chloro-5-ethoxyacetate)-6-phenyl nicotinaldehyde and 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde. 
     In yet another embodiment the activated alkene used is selected from the group consisting of acrylonitrile, methyl acrylate and ethyl acrylate. 
     In yet another embodiment the cyclic enone used is selected from 2-cyclopenten-1-one and 2-cyclohexen-1-one. 
     In yet another embodiment the catalyst used is selected from di azabicylooctane (DABCO) and imidazole. 
     In yet another embodiment the organic solvent used is selected from the group consisting of methanol, ethanol, acetonitrile, tetrahydrofuran, dimethylsulphoxide (DMSO) and dimethylformamide (DMF) 1,4-dioxane, chloroform and sulpholane. 
     In yet another embodiment the molar ratio of 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde to activated alkene or cyclic enone used is in the range of 1:1 to 1:8. 
     In yet another embodiment the molar ratio of 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde to activated alkene in the reaction mixture used is in the range of 1:5 to 1:8. 
     In yet another embodiment the molar ratio of 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde to cyclic enone used is preferably in the range of 1:1 to 1:2. 
     In yet another embodiment the molar ratio of 2-chloro-5 and/or 6-substituted 3-pyridine carboxyaldehyde to catalyst used is in the range of 1:1 to 1:2. 
     In yet another embodiment the molar ratio of activated alkene to catalyst used is in the range of 1:1 to 1:2. 
     In yet another embodiment the reaction mixture of aldehyde and alkene used is diluted with diethyl ether and is followed by washing with water and drying the resultant organic layer over sodium sulphate before subjected to purification by column chromatography. 
     In yet another embodiment the reaction mixture of aldehyde and cyclic-enone is taken into chloroform and the organic layer is washed with brine solution before drying and purification by known method to obtain the desired product. 
     In yet another embodiment the reaction time between aldehyde and cyclic-enone used is in the range of 20-40 minutes. 
     In yet another embodiment the yield of the product chloro pyridine skelton based Baylis-Hillman adduct is in the range of 85-98% without forming side products. 
     In another embodiment, the product chloro pyridine skelton based Baylis-Hillman adduct obtained is selected from the group consisting of 2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ia), 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ib), 2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ic), methyl 6-chloro-5-(2-cyano-1-hydroxy allyl) 2-pyridine carboxylate (Id), Methyl 2-[(2-chloro-5-methylpyridine-3-) (hydroxy)methyl]acrylate (Ie), Methyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (If), 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy) methyl]acrylonitrile (Ig), 2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrle (Ih), Ethyl 6-chloro-5-(2-cyano-1-hydroxy allyl)-2-phenyl-nicotinate (Ii), 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ij), Methyl 2-[(2-chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylate (Ik), Methyl 2-[(2-chloro-5-n-pentyl pyridine-3-yl)(hydroxy)methyl]acrylate (Il), Methyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Im), Methyl 6-chloro-5-[1-hydroxy-2-(methoxycarbonyl)allyl]pyridine-2-carboxylate (In), Ethyl 6-chloro-5-(1-hydroxy-2-(methoxycarbonyl)allyl)-2-phenyl-nicotinate (Io), Methyl 2-[(2-chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Ip), Ethyl 2-[(2-chloro-5-methyl pyridine-3-)(hydroxy)methyl]acrylate (Iq), Ethyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ir), Ethyl 2-[(2-chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Is), Ethyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (It), Methy-6-chloro-5-[1-hydroxy-2-(ethoxycarbonyl)allyl]pyridine-2-carboxylate (Iu), Ethyl 6-chloro-5-(1-hydroxy-2-(ethoxycarbonyl)allyl)-2-phenyl-nicotinate (Iv), Ethyl 2-[(2-chloro-5-(4-meth oxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Iw), 2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIa), 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIb), 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIc), 2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IId), Methyl-6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-pyridinecarboxylate (IIe), Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-phenyl nicotinate (IIf), 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIg), 2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]2-cyclohexene1-one (IIh), 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIi), 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIj), Methyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ik), Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-pyridine carboxylate (IIl), Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-phenyl nicotinate (IIm) and 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one (IIn). 
     In yet another embodiment the chloro pyridine skelton based Baylis-Hillman adduct obtained is active against chloroquine sensitive and chloroquine resistant  plasmodium falciparum  strains. 
     In yet another embodiment the chloro pyridine skelton based Baylis-Hillman adduct obtained exhibits an anti malarial activity against the erythrocytic stage of the malarial parasite. 
     In yet another embodiment the Hillman adduct obtained is used in a pharmaceutical composition comprising novel anti malarial chloro pyridine skelton based Baylis-Hillman adduct, its derivatives, analogues or salt thereof optionally with pharmaceutically acceptable carriers, adjuvant and additives. 
     The present invention is predicted on the discovery that certain Baylis Hillman adducts, preferably in substantially pure form has in vitro antimalarial activity and therefore is useful for malaria treatment. The following preferred embodiments are given by way of illustration of the present invention and therefore should not be constructed to limit the scope of the present invention. Synthetic procedures for representative Baylis Hillman adducts Ia-If are disclosed in the present invention are described below. 
     
       
                 
         
             
             
         
      
     
     If EWG=CN, the activated alkene is called as acrylonitrile 
     If EWG=COOMe, the activated alkene is called as methylacrylate 
     If EWG=COOEt, the activated alkene is called as ethylacrylate 
     
       
                 
         
             
             
         
      
     
     If n=1, then the cyclic-enone is called as 2-cyclopenten-1-one 
     If n=2, then the cyclic-enone is called as 2-cyclohexen-1-one 
     The following examples are given by the way of illustration and therefore should not be construed to limit the scope of the invention 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ia) 
     To a mixture of 2-Chloro-5-methylpyridinecarboxaldehyde (10 mmol, 1.55 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 mL) and washed with water 3×50 mL. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.05 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ib) 
     To a mixture of 2-Chloro-5-ethylnicotinaldehyde (10 mmol, 1.69 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.20 g.). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ic) 
     To a mixture of 2-Chloro-5-phenylnicotinaldehyde (10 mmol, 2.17 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.68 g.). 
     Experimental Procedure for the Synthesis of Methyl 6-chloro-5-(2-cyano-1-hydroxyallyl)2-pyridinecarboxylate (Id) 
     To a mixture of Methyl 6-chloro-5-formyl-2-pyridincarboxylate (10 mmol, 1.99 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.50 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-methylpyridine-3-)(hydroxy)methyl]acrylate (Ie) 
     To a mixture of 2-Chloro-5-methylnicotinaldehyde (10 mmol, 1.55 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.40 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (If) 
     To a mixture of 2-Chloro-5-phenylnicotinaldehyde (10 mmol, 2.17 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.01 g.). 
     Experimental Procedure for the Synthesis of 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ig) 
     To a mixture of 2-Chloro-5-pentylnicotinaldehyde (10 mmol, 2.11 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.62 g.). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrle (Ih) 
     To a mixture of 2-Chloro-5-methyl-6-phenylnicotinaldehyde (10 mmol, 2.31 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.83 g.). 
     Experimental Procedure for the Synthesis of Ethyl 6-chloro-5-(2-cyano-1-hydroxyallyl)-2-phenyl-nicotinate (Ii) 
     To a mixture of 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde (10 mmol, 2.89 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.41 g.). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ij) 
     To a mixture of 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde (10 mmol, 2.45 g) and DABCO (10 mmol. 1.12 g) was added an acrylonitrile (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜4-5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.99 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylate (Ik) 
     To a mixture of 2-Chloro-5-ethylnicotinaldehyde (10 mmol, 1.69 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml.) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.54 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylate (Il) 
     To a mixture of 2-Chloro-5-pentylnicotinaldehyde (10 mmol, 2.11 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.96 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (Im) 
     To a mixture of 2-Chloro-5-methyl-6-phenylnicotinaldehyde (10 mmol, 2.31 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.16 g.). 
     Experimental Procedure for the Synthesis of Methyl 6-chloro-5-[1-hydroxy-2-(methoxycarbonyl)allyl]pyridine-2-carboxylate (In) 
     To a mixture of Methyl 6-chloro-5-formyl-2-pyridincarboxylate (10 mmol, 1.99 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.84 g.). 
     Experimental Procedure for the Synthesis of Ethyl 6-chloro-5-(1-hydroxy-2-(methoxycarbonyl)allyl)-2-phenyl-nicotinate (Io) 
     To a mixture of 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde (10 mmol, 2.89 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.74 g.). 
     Experimental Procedure for the Synthesis of Methyl 2-[(2-chloro-5-(4-methoxy phenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Ip) 
     To a mixture of 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde (10 mmol, 2.45 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.32 g.). 
     Experimental Procedure for the Synthesis of Ethyl 2-[(2-chloro-5-methylpyridine-3-)(hydroxy)methyl]acrylate (Iq) 
     To a mixture of 2-Chloro-5-methylnicotinaldehyde (10 mmol, 1.55 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.54 g.). 
     Experimental Procedure for the Synthesis of Ethyl 2-[(2-chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylate (Ir) 
     To a mixture of 2-Chloro-5-ethylnicotinaldehyde (10 mmol, 1.69 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.68 g.). 
     Experimental Procedure for the Synthesis of Ethyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (Is) 
     To a mixture of 2-Chloro-5-phenylnicotinaldehyde (10 mmol, 2.17 g) and DABCO (10 mmol. 1.12 g) was added an methy/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (316.5 g.). 
     Experimental Procedure for the Synthesis of Ethyl 2-[(2-chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (It) 
     To a mixture of 2-Chloro-5-methyl-6-phenylnicotinaldehyde (10 mmol, 2.31 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.30 g.). 
     Experimental Procedure for the Synthesis of Methy-6-chloro-5-[1-hydroxy-2-(ethoxycarbonyl)allyl]pyridine-2-carboxylate (Iu) 
     To a mixture of Methyl 6-chloro-5-formyl-2-pyridincarboxylate (10 mmol, 1.99 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (2.98 g.). 
     Experimental Procedure for the Synthesis of Ethyl 6-chloro-5-(1-hydroxy-2-(ethoxycarbonyl)allyl)-2-phenyl-nicotinate (Iv) 
     To a mixture of 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde (10 mmol, 2.89 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (3.88 g). 
     Experimental Procedure for the Synthesis of Ethyl 2-[(2-chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Iw) 
     To a mixture of 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde (10 mmol, 2.45 g) and DABCO (10 mmol. 1.12 g) was added an methyl/ethyl acrylate (60 mmol.) under neat conditions [solvent free conditions] at room temperature and the reaction progress was monitored by TLC. Upon completion of the reaction mixture (˜5 min.) was diluted with diethyl ether (300 ml) and washed with water 3×50 ml. The organic layer was dried over Na 2 SO 4  and concentrated, the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane (2:8, v/v) to give the desired product in almost quantitative (346 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIa) 
     The clear solution of 2-Chloro-5-methylnicotinaldehyde (10 mmol, 1.55 g) and imidazole (10 mmol, 0.68 g) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol., 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 98% yield (2.32 g) 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIb) 
     The clear solution of 2-Chloro-5-ethylnicotinaldehyde (10 mmol, 1.69) and imidazole (10 mmol, 0.68 g) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol., 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 97% yield (2.47 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIc) 
     The clear solution of 2-Chloro-5-phenylnicotinaldehyde (10 mmol, 2.17 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol., 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 95% yield (2.84 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IId) 
     The clear solution of 2-Chloro-5-methyl-6-phenylnicotinaldehyde (10 mmol, 2.31 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol., 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 93% yield (2.84 g). 
     Experimental Procedure for the Synthesis of Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-pyridinecarboxylate (IIe) 
     The clear solution of Methyl 6-chloro-5-formyl-2-pyridincarboxylate (10 mmol, 1.99 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol., 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 90% yield (2.53 g). 
     Experimental Procedure for the Synthesis of Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-phenyl nicotinate (IIf) 
     The clear solution of 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde (10 mmol, 2.89 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol. 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 88% yield (3.26 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIg) 
     The clear solution of 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde (10 mmol, 2.45 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclopenten-1-one (10.2 mmol. 0.88 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 90% yield (2.97 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]2-cyclohexene1-one (IIh) 
     The clear solution of 2-Chloro-5-methylnicotinaldehyde (10 mmol, 1.55 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 92% yield (2.22 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIi) 
     The clear solution of 2-Chloro-5-ethylnicotinaldehyde (10 mmol, 1.69 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 95% yield (2.43 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIj) 
     The clear solution of 2-Chloro-5-phenylnicotinaldehyde (10 mmol, 2.17 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 95% yield (2.25 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIk) 
     The clear solution of 2-chloro-substituted-3-pyridinecarboxyaldehyde (10 mmol 2.31 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 90% yield (2.93 g). 
     Experimental Procedure for the Synthesis of Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-pyridine carboxylate (IIl) 
     The clear solution of Methyl 6-chloro-5-formyl-2-pyridincarboxylate (10 mmol, 1.99 g) and imidazole (10 mmol, 0.68 g) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 87% yield (2.56 g). 
     Experimental Procedure for the Synthesis of Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-phenyl nicotinate (IIm) 
     The clear solution of 2-Chloro-5-ethoxyacetate)-6-phenylnicotinaldehyde (10 mmol, 2.89 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAC in hexane as eluent, gave pure Baylis-Hillman adduct in 92% yield (3.5 g). 
     Experimental Procedure for the Synthesis of 2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one (IIn) 
     The clear solution of 2-Chloro-5-(4-methoxyphenyl)-nicotinaldehyde (10 mmol, 2.45 g) and imidazole (10 mmol) in 50 ml. of MeOH was slowly charged with 50 ml. of deionized water. To a stirred homogeneous reaction mixture was added 2-cyclohexen-1-one (10.2 mmol., 1.0 g) at room temperature and reaction progress was monitored by TLC. Upon completion of the reaction, excess MeOH was removed under reduced pressure, washed with water and extracted with CHCl 3  thrice. Combined organic layers were washed with brine solution twice. The organic layer was concentrated and column chromatography of the crude product on silica gel, using 30% EtOAc in hexane as eluent, gave pure Baylis-Hillman adduct in 91% yield (3.13 g). 
     2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ia) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ib) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ic) 
     
       
                 
         
             
             
         
      
     
     Methyl 6-chloro-5-(2-cyano-1-hydroxy allyl) 2-pyridine carboxylate (Id) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-methylpyridine-3-)(hydroxy)methyl]acrylate (Ie) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate (If) 
     
       
                 
         
             
             
         
      
     
     2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ig) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ih) yl)(hydroxy)methyl]acrylonitrile 
     
       
                 
         
             
             
         
      
     
     Ethyl 6-chloro-5-(2-cyano-1-hydroxy allyl)-2-phenyl-nicotinate (Ii) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylonitrile (Ij) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ik) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-n-pentyl pyridine-3-yl)(hydroxy)methyl]acrylate (Il) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Im) 
     
       
                 
         
             
             
         
      
     
     Methyl 6-chloro-5-[1-hydroxy-2-(methoxycarbonyl)allyl]pyridine-2-carboxylate (In) 
     
       
                 
         
             
             
         
      
     
     Ethyl 6-chloro-5-(1-hydroxy-2-(methoxycarbonyl)allyl)-2-phenyl-nicotinate (Io) 
     
       
                 
         
             
             
         
      
     
     Methyl 2-[(2-chloro-5-(4-methoxy phenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Ip) 
     
       
                 
         
             
             
         
      
     
     Ethyl 2-[(2-chloro-5-methyl pyridine-3-)(hydroxy)methyl]acrylate (Iq) 
     
       
                 
         
             
             
         
      
     
     Ethyl 2-[(2-chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]acrylate (Ir) 
     
       
                 
         
             
             
         
      
     
     Ethyl 2-[(2-chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (Is) 
     
       
                 
         
             
             
         
      
     
     Ethyl 2-[(2-chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]acrylate (It) 
     
       
                 
         
             
             
         
      
     
     Methyl 6-chloro-5-[1-hydroxy-2-(ethoxycarbonyl)allyl]pyridine-2-carboxylate (Iu) 
     
       
                 
         
             
             
         
      
     
     Ethyl 6-chloro-5-(1-hydroxy-2-(ethoxycarbonyl)allyl)-2-phenyl-nicotinate (Iv) 
     
       
                 
         
             
             
         
      
     
     Ethyl 2-[(2-chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]acrylate (Iw) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIa) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIb) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIc) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IId) 
     
       
                 
         
             
             
         
      
     
     Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-pyridine carboxylate (IIe) 
     
       
                 
         
             
             
         
      
     
     Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-phenyl nicotinate (IIf) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-(4-methoxyphenyl) pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one (IIg) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-methyl pyridine-3-yl)(hydroxy)methyl]2-cyclohexen-1-one (IIh) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-ethyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIi) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIj) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-methyl-6-phenyl pyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one (IIk) 
     
       
                 
         
             
             
         
      
     
     Methyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-pyridine carboxylate (IIl) 
     
       
                 
         
             
             
         
      
     
     Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-phenyl nicotinate (IIm) 
     
       
                 
         
             
             
         
      
     
     2-[(2-Chloro-5-(4-methoxyphenyl) pyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one (IIn) 
     
       
                 
         
             
             
         
      
     
     The present invention may be better understood by reference to the following non-limiting Examples, which are provided as exemplary of the invention. The following examples are presented in order to more fully illustrate the preferred embodiments of the invention. Synthetic procedures for representative Baylis Hillman adducts Ia-Iw and IIa-IIn were described below. 
     Typical Experimental Procedure for Ia to Iw Using EtOH Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO (1,4-diaza bicyclo[2.2.2]ocatane; 100 mol %) in 5 mL of ethanol was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion (10 min) of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition, the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silicagel, eluting with ethyl acetate and hexane to give the desired product. 
     Typical Experimental Procedure for Ia to Iw Using Acetonitrile Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO [1,4-diaza bicyclo(2.2.2)ocatane] (100 mol %) in 5 mL of acetonitrile was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion (25 min) of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition, the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane to give the desired product in almost quantitative yield. 
     Typical Experimental Procedure for Ia to Iw Using 1,4-Dioxane Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO [1,4-diaza bicyclo(2.2.2)ocatane] (100 mol %) in 5 mL of 1,4-dioxane was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion (12 min) of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition, the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silicagel, eluting with ethyl acetate and hexane to give the desired product in almost quantitative yield. 
     Typical Experimental Procedure for Ia to Iw Using Tetrahydro Furan (THF) Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO [1,4-diaza bicyclo(2.2.2)ocatane] (100 mol %) in 5 mL of THF solvent was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion (20 min), of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition, the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silicagel, eluting with ethyl acetate and hexane to give the desired product in almost quantitative yield. 
     Typical Experimental Procedure for Ia to Iw Using Dimethylformamide (DMF) Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO [1,4-diaza bicyclo(2.2.2)ocatane] (100 mol %) in 5 mL of DMF solvent was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition (12 min), the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silicagel, eluting with ethyl acetate and hexane to give the desired product in almost quantitative yield. 
     Typical Experimental Procedure for Ia to Iw Using Chloroform Solvent System: 
     To a stirred solution of substrate aldehyde (substituted 2-chloro-pyridine-3-carboxyaldehyde) (1 mmol) and DABCO [1,4-diaza bicyclo(2.2.2)ocatane] (100 mol %) in 5 mL of chloroform was added an activated alkene (1.2 mmol) at room temperature and the reaction progress was monitored by TLC. After completion (25 min) of the reaction, the excess solvent was removed under reduced pressure. The obtained residue was diluted with diethyl ether (150 ml.) and brine (50 ml.). After partition, the aqueous layer was extracted with chloroform (2×50 ml.). The combined organic layer was concentrated and the residue was subjected to column chromatography over silica gel, eluting with ethyl acetate and hexane to give the desired product in almost quantitative yield. 
     Typical Experimental Procedure for IIa-IIn Using Aqueous Methanol Solvent System: 
     The clear solution of aldehyde (1 mmol) and imidazole (100 mol %) in 5 ml. of MeOH was slowly charged with 5 ml. of deionized water. To a stirred homogeneous reaction mixture was added cyclic-enone (1.2 mmol.) at room temperature and reaction progress was monitored by TLC for every 5 mins. After completion of the reaction (within 28-30 min), the excess solvent was removed under reduced pressure. The obtained residue was subjected to column chromatography over silica gel using ethylacetate, hexane (30:70, v/v) as eluting solvent system. The desired product was obtained in 82-98% yield. 
     Typical Experimental Procedure for IIa-IIn Using Methanol Solvent System: 
     To a stirred and clear homogeneous solution of aldehyde (1 mmol) and imidazole (100 mol %) in 5 ml. of MeOH was added with cyclic-enone (1.2 mmol.) at room temperature and reaction progress was monitored by TLC for every 5 mins. After completion of the reaction (within 90-120 min), the excess solvent was removed under reduced pressure. The obtained residue was subjected to column chromatography over silica gel using ethylacetate, hexane (30:70, v/v) as eluting solvent system. The desired product was obtained in 82-98% yield. 
     Typical Experimental Procedure for IIa-IIn Using Aqueous Tetrahydro Furan (aq. THF) Solvent System: 
     The clear solution of aldehyde (1 mmol) and imidazole (100 mol %) in 5 ml. of THF was slowly charged with 5 ml. of deionized water. To a stirred homogeneous reaction mixture was added cyclic-enone (1.2 mmol.) at room temperature and reaction progress was monitored by TLC for every 5 mins. After completion of the reaction (within 40-60 min), the excess solvent was removed under reduced pressure. The obtained residue was subjected to column chromatography over silica gel using ethylacetate, hexane (30:70, v/v) as eluting solvent system. The desired product was obtained in 82-98% yield. 
     Typical Experimental Procedure for IIa-IIn Using Aqueous Dimethylformamide (aq. DMF) Solvent System: 
     The clear solution of aldehyde (1 mmol) and imidazole (100 mol %) in 5 ml. of DMF was slowly charged with 5 ml. of deionized water. To a stirred homogeneous reaction mixture was added cyclic-enone (1.2 mmol.) at room temperature and reaction progress was monitored by TLC for every 5 mins. After completion of the reaction (within 45-60 min), the excess solvent was removed under reduced pressure. The obtained residue was subjected to column chromatography over silica gel using ethylacetate, hexane (30:70, v/v) as eluting solvent system. The desired product was obtained in 82-98% yield. 
     Spectral Data: 
     Example Ia 
     2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]acrylonitrile 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.2 (d, 1H), 7.78 (d, 1H), 6.08 (s, 1H), 6.09 (s, 1H), 5.64 (s, 1H), 2.40 (s, 1H);  13 C-NMR: (CDCl 3 , 50 MHz): 148.36, 145.29, 136.96, 132.98, 132.19, 130.29, 124.12, 115.85, 68.60, 16.80; MS (m/z, %): 208, 156, 120, 93, 65, 39. Anal. calcd. for C 10 H 9 ClN 2 O: C, 57.57%; H, 4.34%; N, 13.43%. Found: C, 57.85%; H, 4.68%; N, 13.52%. 
     Example Ib 
     2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylonitrile 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.18 (d, 1H), 7.82 (d, 1H), 6.1 (s, 1H), 6.08 (s, 1H), 5.66 (s, 1H), 2.72 (q, 2H), 1.3 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 148.67, 146.36, 139.52, 136.92, 133.34, 131.59, 124.47, 116.22, 70.06, 25.34, 14.80; MS (EI) m/z: 222 (M + ), 170, 134, 106, 77, 51. Anal. calcd. for C 11 H 11 ClN 2 O: C, 59.31%; H, 5.02%; N, 12.58%. Found: C, 59.70%; H, 5.33%; N, 12.75%. 
     Example Ic 
     2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrile 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.58 (d, 1H), 8.2 (d, 1H), 7.4-7.6 (m, 5H), 6.14 (s, 1H), 6.1 (s, 1H), 5.66 (s, 1H).  13 C-NMR: (CDCl 3 , 50 MHz): δ 70.37, 116.18, 124.13, 127.18, 128.78, 129.27, 132.05, 133.33, 135.57, 135.94, 136.82, 147.68; MS (EI) m/z: 270 (M+), 245, 218, 182, 154, 141, 77; Anal. calcd. for C 15 H 11 ClN 2 O: C, 66.53%; H, 4.13%; N, 10.34%. Found: C, 66.67%; H, 4.38%; N, 10.70%. 
     Example Id 
     Methyl 6-chloro-5-(2-cyano-1-hydroxyprop-2-en-1-yl)pyridine-2-carboxylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.15 (d, 1H), 8.22 (d, 1H), 6.1 (d, 2H), 5.73 (d, 1H), 3.98 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 164.05, 149.01, 147.33, 138.36, 137.96, 132.63, 124.42, 123.52, 115.98, 69.99, 53.19; MS (EI) m/z: 252 (M+), 222, 200, 194, 164, 112, 76, 59. Anal. calcd. for C 11 H 9 ClN 2 O 3 : C, 52.29%; H, 3.59%; N, 11.09%. Found: C, 52.56%; H, 3.68%; N, 11.34%. 
     Example Ie 
     Methyl 2-[(2-chloro-5-methylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.11 (d, 1H), 7.71 (d, 1H), 6.32 (s, 1H), 5.8 (s, 1H), 5.56 (s, 1H), 3.8 (s, 3H), 2.35 (s, 3H);  13 C-NMR (CDCl 3 , 50 MHz): δ 166.06, 148.17, 146.52, 140.25, 137.85, 134.85, 132.44, 126.73, 67.89, 51.70, 17.34; MS (m/z, %): 241, 206, 156, 120, 92, 65. Anal. calcd. for C 11 H 12 ClNO 3 : C, 54.68%; H, 4.99%; N, 5.80%. Found: C, 54.86%; H, 5.10%; N, 5.98%. 
     Example If 
     Methyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.48 (d, 1H), 8.12 (d, 1H), 7.34-7.58 (m, 5H), 6.34 (s, 1H), 5.88 (s 1H), 5.62 (s, 1H), 4.18 (b, 1H), 3.77 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.60, 148.39, 146.67, 139.91, 136.23, 136.06, 135.70, 135.13, 129.08, 128.44, 127.49, 127.00, 68.98, 52.13; MS (EI) m/z: 303 (M+), 268, 236, 218, 182, 153, 127, 115, 77, 55. Anal. calcd. for C 16 H 14 ClNO 3 : C, 63.24%; H, 4.68%; N, 4.61%. Found: C, 63.42%; H, 4.88%; N, 4.86%. 
     Ig: 
     2-[(2-Chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylonitrile 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.18 (s, 1H), 7.8 (s, 1H), 6.45 (s, 1H), 6.5 (s, 1H), 5.62 (s, 1H), 2.62 (t, 2H), 1.23-1.65 (m, 6H), 0.95 (t, 3H); MS EI (m/z): 264 (M+), 212, 176, 41; Anal. calcd. for C 14 H 17 ClN 2 O: C, 63.51%; H, 6.47%; N, 10.58%. Found: C, 63.96%; H, 6.88%; N, 10.92% 
     Ih: 
     2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylonitrile 
     1H-NMR (CDCl 3 , 200 MHz): δ 7.82 (s, 1H), 7.35-7.55 (m, 5H), 6.07 (s, 1H), 6.1 (s, 1H), 5.62 (s, 1H), 2.4 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 158.71, 145.64, 139.69, 138.23, 131.72, 130.98, 128.81, 128.64, 128.25, 124.19, 116.36, 69.67, 19.27; MS (EI) m/z: 284 (M+), 232, 196, 168, 119, 77, 52, 39. Anal. calcd. for C 16 H 13 ClN 2 O: C, 67.48%; H, 4.60%; N, 9.84%. Found: C, 67.69%; H, 4.82%; N, 10.01%. 
     Ii: 
     Ethyl 6-chloro-5-(2-cyano-1-hydroxy allyl)-2-phenyl-nicotinate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.82 (s, 1H), 7.6 (m, 2H), 7.42 (m, 3H), 6.04 (s, 2H), 5.63 (s, 1H), 5.4 (b, 1H), 4.21 (q, 2H), 1.25 (t, 3H); MS (EI) m/z: 342 (M+), 307, 262, 254, 179, 77; Anal. calcd. for C 18 H 15 ClN 2 O 3 : C, 63.07%; H, 4.41%; N, 8.17%. Found: C, 62.88%; H, 4.65%; N, 8.47%. 
     Ij: 
     2-{[2-Chloro-5-(4-methoxyphenyl)-pyridine-3-yl](hydroxy)methyl}acrylonitrile 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.5 (s, 1H), 8.12 (s, 1H), 7.5 (m, 2H), 6.95 (m, 2H), 6.11 (d, 2H), 5.71 (s, 1H), 3.84 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 160.23, 147.08, 136.39, 135.00, 133.34, 131.96, 128.26, 124.15, 116.26, 114.72, 70.23, 55.38; MS (EI) m/z: 300 (M+), 248, 212, 185, 107, 65; Anal. calcd. for C 16 H 13 ClN 2 O 2 : C, 63.90%; H, 4.36%; N, 9.31%. Found: C, 64.01%; H, 4.54%; N, 9.46%. 
     Ik: 
     Methyl 2-[(2-chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.15 (d, 1H), 7.77 (d, 1H), 6.32 (s, 1H), 5.81 (s, 1H), 5.51 (s, 1H), 3.81 (s, 3H), 2.7 (q, 3H), 1.3 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 167.39, 149.27, 147.78, 140.28, 139.62, 137.77, 129.62, 126.34, 69.79, 51.60, 25.76, 14.72; MS (EI) m/z: 222 (M+), 187, 173, 102, 65; Anal. calcd. for C 12 H 14 ClNO 3 : C, 56.37%, H, 5.52%, N, 5.19%. Found: C, 56.78%, H, 5.89%, N, 5.62%. 
     Il: 
     Methyl 2-[(2-chloro-5-n-pentylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.1 (s, 1H), 7.68 (s, 1H), 6.22 (s, 1H), 5.78 (s, 1H), 5.23 (s, 1H), 3.78 (s, 3H), 2.58 (t, 2H), 1.2-1.65 (m, 6H), 0.9 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.59, 148.29, 146.86, 140.06, 137.50, 134.62, 127.19, 68.80, 52.02, 32.11, 31.12, 30.46, 22.24, 13.93, 13.80; MS (EI) m/z: 297 (M+), 282, 224, 189, 155, 71; Anal. calcd. for. C 15 H 20 ClNO 3 : C, 60.50%; H, 6.77%; N, 4.70%. Found: C, 60.56%; H, 6.89%; N, 4.85%. 
     Im: 
     Methyl 2-[(2-chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 7.78 (s, 1H), 7.35-7.55 (m, 5H), 6.37 (s, 1H), 5.82 (s, 1H), 5.65 (s, 1H), 3.82 (b, 1H), 2.4 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.69, 157.90, 146.34, 139.94, 139.77, 138.68, 133.03, 130.22, 128.94, 128.35, 128.12, 127.34, 68.91, 52.11, 19.33; MS (EI) m/z: 317 (M+), 302, 2282, 250, 230, 196, 167, 141, 117; Anal. calcd. for C 17 H 16 ClNO 3 : C, 64.26%; H, 5.07%; N, 4.41%. Found: C, 64.77%; H, 5.24%; N, 4.52%. 
     In: 
     Methyl 6-chloro-5 [1-hydroxy-2-(methoxycarbonyl)prop-2-en-1-yl]pyridine-2-carboxylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.12 (m, 2H), 6.32 (s, 1H), 5.82 (s, 1H), 5.52 (s, 1H), 3.98 (s, 3H), 3.78 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.44, 164.30, 149.60, 147.02, 139.43, 138.26, 127.81, 124.00, 69.09, 52.99, 52.21; MS (EI) m/z: 285 (M+), 250, 217, 197, 164, 140, 115, 83, 59; Anal. calcd. for C 12 H 12 ClNO 5 : C, 50.45%; H, 4.23%; N, 4.41%. Found: C, 50.89%; H, 4.44%; N, 4.67%. 
     Io: 
     Ethyl 6-chloro-5-(1-hydroxy-2-(methoxycarbonyl)allyl)-2-phenyl-nicotinate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.8 (s, 1H), 7.62 (m, 2H), 7.4 (m, 3H), 6.41 (s, 1H), 5.98 (s, 1H), 5.78 (s, 1H), 4.2 (q, 2H), 3.68 (s, 3H), 1.25 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz 165.57, 156.43, 149.39, 140.64, 139.61, 137.86, 133.07, 129.35, 128.99, 128.38, 128.28, 127.65, 67.95, 62.17, 52.14, 29.58, 13.55; MS (EI) m/z: 375 (M+), 330, 313, 299, 257, 165, 77; Anal. calcd. for: C 19 H 18 ClNO 5 : C, 60.73%; H, 4.83%; N, 3.72%. Found: C, 60.89%; H, 4.99%; N, 3.87%. 
     Ip: 
     Methyl 2-{[2-chloro-5-(4-methoxyphenyl)-pyridine-3-yl](hydroxy)methyl}acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.49 (s, 1H), 8.1 (s, 1H), 7.5 (m, 2H), 6.98 (m, 2H), 6.38 (s, 1H), 5.9 (s, 1H), 5.65 (s, 1H), 3.85 (s, 3H), 3.8 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.61, 160.00, 147.58, 146.17, 139.88, 135.70, 135.19, 135.00, 128.12, 127.48, 114.80, 114.57, 68.96, 60.33, 55.30, 52.14, 24.58; MS (EI) m/z: 333 (M+), 299, 273, 248, 212, 170, 141, 99, 43; Anal. calcd. for C 17 H 16 ClNO 4 : C, 61.18%; H, 4.83%; N, 4.20%. Found: C, 61.45%; H, 4.99%; N, 4.67%. 
     Iq: 
     Ethyl2-[(2-chloro-5-methylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): 8.06 (d, 1H), 7.66 (d, 1H), 6.28 (s, 1H), 5.76 (s, 1H), 5.55 (s, 1H), 4.16 (q, 2H), 2.30 (s, 3H), 1.25 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.30, 148.83, 148.89, 140.15, 137.98, 134.49, 132.70, 127.37, 127.08, 69.08, 61.23, 17.70, 14.06; MS EI (m/z): 255 (M + ), 220, 192, 154, 146, 120, 92, 65. Anal. calcd. for C 12 H 14 ClNO 3 : C, 56.35%; H, 5.55%; N, 5.48%. Found: C, 56.66%; H, 5.74%; N, 5.62%. 
     Ir: 
     Ethyl 2-[(2-chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.13 (d, 1H), 7.66 (d, 1H), 6.28 (s, 1H), 5.75 (s, 1H), 5.28 (s, 1H), 4.25 (q, 2H), 2.64 (q, 2H), 1.2o (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 167.65, 151.26, 147.68, 140.32, 139.62, 136.73, 128.75, 125.36, 70.78, 60.92, 25.96, 17.12, 14.12; MS EI (m/z): 269 (M + ), 234, 204, 166, 132, 104, 79; Anal. calcd. for C 13 H 16 ClNO 3 : C, 57.89%; H, 5.98%; N, 4.2%. Found: C, 58.12%; H, 6.22%; N, 4.36%. 
     Is: 
     Ethyl 2-[(2-chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.5 (d, 1H), 8.12 (s, 1H), 7.35-7.6 (m, 5H), 6.34 (s, 1H), 5.88 (s, 1H), 5.62 (s, 1H), 4.3 (q, 2H), 3.88 (b, 1H), 1.3 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 166.65, 148.89, 147.12, 140.62, 136.74, 136.54, 136.18, 135.65, 129.55, 128.90, 127.61, 127.47, 69.61, 61.68, 14.43; MS (EI) m/z: 317 (M+), 302, 282, 268, 254, 216, 182, 153, 127, 115, 77, 55. Anal. calcd. for C 17 H 16 ClNO 3 : C, 64.26%; H, 5.07%; N, 4.40%. Found: C, 64.53%; H, 5.25; N, 4.62%. 
     It: 
     Ethyl 2-[(2-chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): 7.78 (s, 1H), 7.35-7.55 (m, 5H), 6.38 (s, 1H), 5.82 (s, 1H), 5.62 (s, 1H), 4.25 (q, 2H), 2.4 (s, 3H), 1.33 (t, 3H); δ  13 C-NMR: (CDCl 3 , 50 MHz): δ 167.65, 156.35, 145.87, 140.87, 138.67, 137.67, 135.42, 129.87, 127.93, 127.56, 124.42, 70.91, 54.64, 20.12, 14.56; MS (EI) m/z: 331 (M+), 302, 231, 165, 77; Anal. calcd. for C 18 H 18 ClNO 3 : C, 65.16%; H, 5.47%; N, 4.22%. Found: C, 65.45%; H, 4.56%; N, 4.44%; 
     Iu: 
     Methyl 6-chloro-5[1-hydroxy-2-(ethoxycarbonyl)prop-2-en-1-yl]pyridine-2-carboxylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.12 (sharp q, 2H), 6.32, (s, 1H), 5.85 (s, 1H), 5.52 (s, 1H), 4.25 (q, 2H), 3.98 (s, 1H), 3.70 (b, 1H), 1.32 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 165.79, 164.20, 149.58, 146.75, 139.81, 139.75, 138.20, 127.32, 123.89, 68.77, 61.16, 52.89, 13.85; 
     MS (EI) m/z: 299 (M+), 264, 219, 178, 129; Anal. calcd. for C 13 H 14 ClNO 5 : C, 52.10%; H, 4.71%; N, 4.67%. Found: C, 52.43%; H, 4.97%; N, 4.86%. 
     Iv: 
     Ethyl 6-chloro-5-(1-hydroxy-2-(ethoxycarbonyl)allyl)-2-phenyl-nicotinate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.8 (s, 1H), 7.61 (m, 2H), 7.4 (m, 3H), 6.40 (s, 1H), 5.99 (s, 1H), 5.77 (s, 1H), 4.25 (q, 2H), 4.2 (q, 2H), 1.32 (t, 3H), 1.25 (t, 3H); MS (EI) m/z: 389 (M+), 354, 306, 209, 165, 77; Anal. calcd. for C 20 H 20 ClNO 5 : C, 61.61%; H, 5.17%; N, 3.59%. Found: C, 61.89%; H, 5.64%; N, 3.82%. 
     Iw: 
     Ethyl 2-{[2-chloro-5-(4-methoxyphenyl)-pyridine-3-yl](hydroxy)methyl}acrylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.48 (s, 1H), 8.12 (s, 1H), 7.5 (m, 2H), 6.98 (m, 2H), 6.39 (s, 1H), 5.91 (s, 1H), 5.66 (s, 1H), 4.25 (q, 2H), 1.32 (t, 3H); MS (EI) m/z: 347 (M+), 312, 213, 239, 181, 176, 107, 65; Anal. calcd. for C 18 H 18 ClNO 4 : C, 62.16%; H, 5.22%; N, 4.03%. Found: C, 62.28%; H, 5.56%; N, 4.23%. 
     IIa: 
     2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.16 (d, 1H), 7.82 (d, 1H), 7.14 (sharp t, 1H), 5.78 (s, 1H), 4.18 (d, 1H), 2.65 (m, 2H), 2.52 (m, 2H), 2.4 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 209.59, 160.53, 148.72, 146.06, 144.98, 137.62, 134.93, 132.85, 65.65, 35.07, 26.69, 17.73; MS EI (m/z): 237 (M + ), 202, 156, 117, 92, 39. Anal. calcd. for C 12 H 12 ClNO 2 : C, 60.61%; H, 5.13%; N, 5.89%. Found: C, 60.80%; H, 5.23%; N, 5.98%. 
     IIb: 
     2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.18 (d, 1H), 7.78 (d, 1H), 7.21 (t, 1H), 5.58 (s, 1H), 4.25 (b, 1H), 2.66 (q, 2H), 2.4 (m, 2H), 2.54 (m, 2H), 1.29 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 207.82, 150.62, 149.74, 148.54, 139.76, 138.28, 133.21, 128.66, 65.42, 38.92, 25.88, 23.25, 14.95; MS EI (m/z): 251 (M + ), 216, 170, 131, 104, 53; Anal. calcd. for C 13 H 14 ClNO 2 : C, 62.03%; H, 5.61%; N, 5.56%. Found: C, 62.44%, H, 5.98%; N, 14.56%. 
     IIc: 
     2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.53 (s, 1H), 8.21 (s, 1H), 7.36-7.55 (m, 5H), 7.19 (sharp t, 1H), 5.85 (s, 1H), 2.46-2.72 (m, 4H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 205.82, 152.12, 149.75, 138.92, 138.48, 136.18, 130.14, 125.51, 124.91, 59.77, 45.08, 23.55; MS (EI) m/z: 299 (M+), 264, 236, 153, 77; Anal. calcd. for C 17 H 14 ClNO 2 : C, 68.18%; H, 4.70%; N, 4.67%. Found: C, 68.24%; H, 4.83%; N, 4.87%. 
     IId: 
     2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 7.85 (s, 1H), 7.35-7.55 (m, 5H), 7.25 (sharp t, 1H), 5.82 (s, 1H), 4.09 (d, 1H), 2.62-2.68 (m, 2H), 2.48-2.55 (m, 2H), 2.4 (s, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 210.02, 160.43, 157.93, 145.54, 144.70, 139.45, 138.81, 133.34, 130.44, 128.97, 128.39, 128.19, 66.19, 35.11, 26.72, 19.39; MS (EI) m/z: 313 (M+), 278, 50, 235, 193, 115, 77; Anal. calcd. for C 18 H 16 ClNO 2 : C, 68.90%; H, 5.14%; N, 4.46%. Found: C, 69.12%; H, 5.43%; N, 4.76%. 
     IIe: 
     Methyl-6-chloro-5-[hydroxy(5-oxo-cyclopent-1-en-1-yl)methyl]pyridine-2-carboxylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.13 (d, 1H), 8.25 (d, 1H), 7.22 (sharp t, 1H), 5.88 (s, 1H), 3.98 (s, 3H), 2.65 (m, 2H), 2.5 (m, 2H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 199.93, 164.33, 149.16, 148.69, 146.77, 139.95, 138.26, 123.94, 68.52, 52.93, 38.23, 25.74, 22.25; MS (EI) m/z: 281 (M+), 246, 218, 202, 188, 122, 69; Anal. calcd. for C 13 H 12 ClNO 4 : C, 55.43%; H, 4.29%; N, 4.97%. Found: C, 55.67%; H, 4.67%; N, 5.14%. 
     IIf: 
     Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclopentenyl)methyl]-2-phenyl nicotinate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.9 (s, 1H), 7.6 (m, 2H), 7.42 (m, 3H), 7.22 (t, 1H), 5.92 (s, 1H), 4.2 (q, 2H), 2.65 (m, 2H), 2.5 (t, 2H), 1.1 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 205.82, 167.64, 149.25, 149.18, 139.80, 139.22, 136.43, 134.40, 132.7, 129.11, 128.36, 123.26, 117.75, 60.49, 57.2, 45.02, 23.25, 14.35; MS (EI) m/z: 371 (M+), 336, 318, 275, 263, 178, 77; Anal. calcd. for C 20 H 18 ClNO 4 : C, 64.61%; H, 4.88%; N, 3.77%. Found: C, 64.92%; H, 5.09%; N, 3.78%. 
     IIg: 
     2-[(2-Chloro-5-(4-methoxyphenyl) pyridine-3-yl)(hydroxy)methyl]cyclopent-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.43 (d, 1H), 8.13 (d, 1H), 7.49 (m, 2H), 7.18 (t, 1H), 6.92 (m, 3H), 5.8 (s, 1H), 3.82 (s, 3H), 2.53 (m, 2H), 2.45 (m, 2H); MS (EI) m/z: 329 (M+), 294, 276, 251, 107, 65; Anal. calcd. for C 18 H 16 ClNO 3 : C, 65.56%; H, 4.89%; N, 4.25%. Found: C, 65.87%; H, 5.12%; N, 4.45%. 
     IIh: 
     2-[(2-Chloro-5-methylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.1 (d, 1H), 7.78 (d, 1H), 6.46 (t, 1H), 5.72 (s, 1H), 2.5 (m, 2H), 2.36 (s, 3H), 2.38 (m, 2H), 2.03 (m, 2H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 200.24, 148.49, 148.22, 138.70, 137.95, 134.73, 132.55, 68.37, 38.34, 25.74, 22.35, 17.70; MS EI (m/z): 251 (M + ), 216, 198, 116, 84, 65, 48. Anal. calcd. for C 13 H 14 ClNO 2 : C, 62.01%; H, 5.64%; N, 5.56. Found: C, 62.24%; H, 5.74%; N, 5.68%. 
     IIi: 
     2-[(2-Chloro-5-ethylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-ene-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.14 (d, 1H), 7.76 (d, 1H), 6.5 (t, 1H), 5.72 (s, 1H), 4.22 (b, 1H), 2.64 (q, 2H), 2.5 (m, 2H), 2.38 (m, 2H), 2.02 (m, 2H), 1.18 (t, 3H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 200.23, 149.42, 148.86, 139.06, 138.76, 135.32, 134.17, 128.13, 67.75, 38.03, 25.86, 25.78, 22.34, 14.95; MS (m/z, %): 265, 230, 212, 130, 98, 79, 62; Anal. calcd. for C 14 H 16 ClNO 2 : C, 63.28%; H, 6.07%; N, 5.27%. Found: C, 63.54%, H, 6.42%; N, 5.44%. 
     IIj: 
     2-[(2-Chloro-5-phenylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.5 (s, 1H), 8.2 (s, 1H), 7.34-7.64 (m, 5H), 6.5 (t, 1H), 5.8 (s, 1H), 3.85 (b, 1H), 2.05 (m, 2H), 2.35-2.6 (m, 4H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 200.29, 148.46, 148.00, 146.42, 138.64, 136.41, 136.01, 135.79, 135.39, 129.07, 128.39, 127.06, 68.53, 38.33, 25.76, 22.34. MS (EI) m/z: 313 (M+), 278, 260, 217, 71, 57; Anal. calcd. for C 18 H 16 ClNO 2 : C, 68.90%; H, 5.14%; N, 4.46%. Found: C, 69.12%; H, 5.27%; N, 4.48%. 
     IIk: 
     2-[(2-Chloro-5-methyl-6-phenylpyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 7.85 (s, 1H), 7.35-7.55 (m, 5H), 6.66 (t, 1H), 5.75 (s, 1H), 3.86 (d, 1H), 2.5 (m, 2H), 2.4 (m, 2H), 2.4 (s, 3H), 2.0 (m, 2H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 200.29, 148.46, 148.00, 146.42, 138.64, 136.41, 136.01, 135.79, 135.39, 129.07, 128.39, 127.06, 68.53, 38.33, 25.76, 22.34; MS (EI) m/z: 327 (M + ), 311, 291, 273, 249, 218, 117; Anal. calcd. for C 19 H 18 ClNO 2 : C, 69.62%; H, 5.53%; N, 4.27%. Found: C, 70.07%; H, 5.74%; N, 4.56%. 
     IIl: 
     Methyl-6-chloro-5-[hydroxy(6-oxo-cyclohex-1-en-1-yl)methyl]pyridine-2-carboxylate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.12 (d, 2H), 8.02 (d, 1H), 6.52 (t, 1H), 5.83 (s, 1H), 3.98 (s, 3H), 2.5 (m, 2H), 2.4 (m, 2H), 2.05 (m, 2H);  13 C-NMR: (CDCl 3 , 50 MHz): δ 199.93, 164.33, 149.16, 148.69, 146.77, 139.95, 138.26, 123.94, 68.53, 52.93, 38.23, 25.74, 22.25; MS (EI) m/z: 295 (M+), 260, 232, 229, 201, 160, 112, 59; Anal. calcd. for C 14 H 14 ClNO 4 : C, 56.86%; H, 4.77%; N, 4.74%. Found: C, 57.12%; H, 4.98%; N, 4.98%. 
     IIm: 
     Ethyl 6-chloro-5-[hydroxy(5-oxo-1-cyclohexenyl)methyl]-2-phenyl nicotinate 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.92 (s, 1H), 7.6 (m, 2H), 7.4 (m, 3H), 6.59 (t, 1H), 5.98 (s, 1H), 4.2 (q, 2H), 2.38-2.57 (m, 4H), 2.02 (m, 2H), 1.1 (t, 3H); MS (EI) m/z: 385 (M+), 350, 332, 321, 278, 165, 73; Anal. calcd. for C 21 H 20 ClNO 4 : C, 65.37%; H, 5.22%; N, 3.63%. Found: C, 65.78%; H, 5.67%; N, 3.78%. 
     IIn: 
     2-[(2-Chloro-5-(4-methoxyphenyl)pyridine-3-yl)(hydroxy)methyl]cyclohex-2-en-1-one 
       1 H-NMR (CDCl 3 , 200 MHz): δ 8.45 (s, 1H), 8.13 (s, 1H), 7.5 (d, 2H), 6.95 (d, 2H), 6.55 (t, 1H), 5.78 (s, 1H), 3.82 (s, 3H), 2.3-2.6 (m, 4H), 2.02 (m, 2H); MS (EI) m/z: 343 (M+), 308, 290, 247, 107, 65; Anal. calcd. for C 19 H 18 ClNO 3 : C, 66.38%; H, 5.28%; N, 4.07%. Found: C, 66.97%; H, 5.56%; N, 4.34%. 
     Antimalarial Activity: 
     Parasites were cultured in O (+) erythrocytes in RPMI-1640 media supplemented with 25 mM HEPES buffer and 10% AB (+) serum by candlejar technique. 9  Initial culture was maintained in small vials (2.5 cm dia.) with 10% haematocrit, i.e. 10 μl erythrocytes containing 1.5% ring stage parasite in 100 μl complete media. The culture volume per well for the assay was 100 μl. Parasitamia was determined for each set of culture, number of parasites for the assay were adjusted at 1 to 1.5% by diluting with fresh O (+) RBC. Assay was done in 96 well microtitre flat-bottomed tissue culture plates. Parasite culture was synchronized at ring forms using density gradient method 10  and cultured for 24 h. in the presence of various doses of compounds and chloroquine for their effect in schizont maturation. Test was done in duplicate wells for each dose of the drugs. Control culture was done with RPMI-164 containing 10% AB (+) serum. Growth of the parasites from duplicate wells of each concentration was monitored in JSB stained 11  blood smears by counting number of schizont per 200 asexual parasites. Percent schizont maturation inhibition was calculated by the formula: (1−N t /N c )×100 where, N t  and N c  represent the number of schizont in the test and control well respectively. The effects on parasite growth by the compounds (Ia-If) of the present invention, together with data are shown in tables 1 and 2 respectively. 
     
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Antimalarial activities, IC 50  and IC 90  of compounds Ia-If against 
               
               
                 Chloroquine sensitive (CQS)  P. falciparum  strain 
               
               
                 Inhibitory activity in μg/ml 
               
             
          
           
               
                   
                 IC50 
                   
                 IC90 
                   
               
             
          
           
               
                 Compounds 
                 SMI 
                 PGI 
                 SMI 
                 PGI 
               
               
                   
               
             
          
           
               
                 Ia 
                 1.25 
                 1.3 
                 25.5 
                 85 
               
               
                 Ib 
                 1.8 
                 4 
                 15.5 
                 31 
               
               
                 Ic 
                 3.6 
                 8 
                 25.5 
                 23 
               
               
                 Id 
                 3.4 
                 7 
                 22 
                 29 
               
               
                 Ie 
                 18 
                 28.5 
                 32 
                 115 
               
               
                 If 
                 45 
                 115 
                 125 
                 350 
               
               
                   
               
               
                 SMI: Schizont maturation inhibition determined after 24 hr. 
               
               
                 PGI: Total parasite growth inhibition determined after 48 hr. 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Antimalarial activities, IC 50  and IC 90  of compounds Ia-If against 
               
               
                 Chloroquine resistant (CQR)  P. falciparum  strain 
               
               
                 Inhibitory activity in μg/ml 
               
             
          
           
               
                   
                 IC50 
                   
                 IC90 
                   
               
             
          
           
               
                 Compounds 
                 SMI 
                 PGI 
                 SMI 
                 PGI 
               
               
                   
               
             
          
           
               
                 Ia 
                 22.5 
                 10.5 
                 125 
                 300 
               
               
                 Ib 
                 2.5 
                 5.5 
                 6.5 
                 26 
               
               
                 Ic 
                 0.9 
                 2.2 
                 1.5 
                 6.75 
               
               
                 Id 
                 5.75 
                 6.75 
                 25.5 
                 29 
               
               
                 Ie 
                 3.05 
                 5.75 
                 7 
                 27.5 
               
               
                 If 
                 5 
                 10.75 
                 30 
                 77.5 
               
               
                   
               
               
                 SMI: Schizont maturation inhibition determined after 24 hr. 
               
               
                 PGI: Total parasite growth inhibition determined after 48 hr.