Patent Description:
Cancer is a condition in which abnormal cells proliferate and spread at any place in the body. In other words, cancer is an uncontrolled growth of abnormal cells. Cancer is a leading cause of death worldwide. It remains the second most dreadful disease in India, killing more than three million patients each year. It is of major concern in India and is reported to be one of the ten leading causes of deaths in India.

While molecularly-targeted therapies are available for treatment of cancer for a high price, majority of the world population rely on standard chemotherapy. The standard anticancer regiment targets most of the dividing cancer cells and not quiescent or slow-dividing cancer stem cells (CSCs). Even though, CSCs have been identified a while ago, scientists around the globe are still looking to find CSC-targeted agents and unfortunately, until today, there is none available in the market to specifically target CSCs.

CSCs and work either alone or in combination with the standard therapies to provide effective treatment option for the cancer patients.

The following describe compounds for use in the treatment of cancer: <CIT>; <CIT>; <CIT>; <NPL>; <NPL>; <NPL>; <NPL>; <CIT>; and <CIT>. The following describe various chemical compounds: <NPL>; <CIT>; <NPL>; <CIT>; <NPL>; and <NPL>.

The dependent claims depict other embodiments of the invention. Any embodiment not falling under the scope of the appended claims does not form part of the invention.

The present invention provides compounds for the treatment of cancer. particularly cancer stem cells that show preferential toxicity towards malignant cells, particularly in cancer cell lines such as breast cancer, and/or prostate cancer cell lines.

In one aspect of the present invention, compound of Formula IV is provided:
<CHM>
where R<NUM> and R<NUM> are each independently selected from -H, -OMe-; R is selected from:
<CHM>
wherein, R<NUM> is -OH; R<NUM> is selected from -OMe, -OH; R<NUM> is selected from - OMe, -OH; R<NUM> is -H; R<NUM> is -CH<NUM>; R<NUM> and R<NUM> are each independently selected from -H, or R<NUM> and R<NUM> together form lactone, or -C(O)OC<NUM>H<NUM>; and wherein the compound is selected from:
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>.

In a preferred embodiment of the invention, compound of Formula V is provided:
<CHM>.

In another preferred embodiment, compound of Formula VI is provided:
<CHM>.

In another embodiment, compound of Formula VII is provided:
<CHM>.

In another embodiment, compound of Formula VIII is provided:
<CHM>.

In a further embodiment, compound of Formula IX is provided:
<CHM>.

In a further embodiment, a compound of Formula X is provided:
<CHM>.

In a further embodiment, a compound of Formula XI is provided:
<CHM>.

A second aspect of the invention provides compounds V to XI for use in the treatment of cancer.

In an embodiment of the present invention, compounds of Formula V or VI are provided for use in the treatment of cancer. In an embodiment, the cancer is breast, oral, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, or stomach cancer.

In a preferred embodiment of the present invention, the compounds of Formula V or VI are for use in the treatment of breast and/or prostate cancer.

In yet another aspect of the present invention, a pharmaceutical composition having a compound of Formula V to Formula XI and pharmaceutically acceptable excipient including carrier, adjuvant, vehicle or mixtures thereof is provided. In an embodiment, the pharmaceutical composition of the present invention is for use in the treatment of cancer including breast, oral, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, or stomach cancer. In a preferred embodiment, the composition is used for the treatment of breast and/or prostate cancer.

The present disclosure relates to compounds for treating various conditions, particularly for inhibition of uncontrolled cell proliferation. Particularly the compounds are effective against cancer stem cells and treating cancer. Described herein are compounds of Formula <NUM>:
<CHM>
wherein, R<NUM> is selected from -H, -CH<NUM>OH; R<NUM> is selected from -H, -OH, alkoxy, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is selected from alkoxy, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is selected from -OH, F, -NH<NUM>, -NHCOCH<NUM>, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is H, Cl; R<NUM> and R<NUM> each independently is selected from H, alkyl, substituted or unsubstituted aromatic group, alkoxy, NH<NUM>, NO<NUM>, -NHCOCH<NUM>, - CN, -O-, halogen, -OCF<NUM> or R<NUM> and R<NUM> together form a heterocyclic ring; R<NUM> is H, Cl; R<NUM> is selected from a substituted or unsubstituted <NUM>- or <NUM>-membered ring, - CH<NUM>-O-CH<NUM>-COOH R<NUM> is =O or H; A is O, -NH, -N-alkyl; Q is O, S, -CH<NUM>O-; X is selected from CH<NUM>, O, N, S; E is selected from CH, O, N, S; and Z is selected from CH, O, N, S. In one example, the R<NUM> group is
<CHM>.

Also described herein is a compound of formula II:
<CHM>.

Further described herein are compounds of Formula III or salts thereof for treating various conditions, particularly for inhibition of uncontrolled cell proliferation. Particularly, the compounds are effective against cancer stem cells. <CHM>
wherein, E and Z is selected from C, O, N, S, salts of N such as N. HCl; Q is O, S, -CH<NUM>O-, -NY', wherein Y' is selected from -H, alkyl; SOOCH3; R<NUM> is -H, -Cl, when E and/or Z is -C; R<NUM> and R<NUM> each independently is selected from -H, alkoxy, alkyl, substituted or unsubstituted aromatic group, -NH<NUM>, -NO<NUM>, - NHCOCH<NUM>, -CN, -O-, halogen, -OCF<NUM> or R<NUM> and R<NUM> together form a heterocyclic ring; R<NUM> is -H, -Cl, when E and/or Z is -C; R<NUM> is -CH2-O-CH2, -COOH, -X where X can be F, Cl, Br, alkyl such as -CH<NUM>, -OH, alkoxy such as -OMe, NHCOCH<NUM>, H, NH<NUM>; R<NUM> and R<NUM> each independently is selected from -H, R<NUM> and R<NUM> can be substituted or unsubstituted <NUM>- or <NUM>- membered ring such as lactone, -C(O)O-alkyl such as -C(O)OC<NUM>H<NUM>; R is selected from:
<CHM>
<CHM>
-H, -C(O)CH<NUM>Cl, - SOO-CH<NUM>, -SOOPh, , -CH<NUM>C(O)N(CH<NUM>)<NUM>, -C(O)NHPh, -C(O)NHPhOH, - C(S)NHPh, -CH<NUM>Ph, -COAr, -SOOAr, -CONHAr, -CH<NUM>Ar, -CSNHAr, wherein, R<NUM> is selected from -OH, -NH<NUM>, -NHCOCH<NUM>, X = F, Cl, Br, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is selected from alkoxy, -OMe, -OH, NH<NUM>, - NHCOCH<NUM>, X = F, Cl, Br, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is selected from alkoxy, -OMe, -OH, -H, Br, NH<NUM>, X = F, Cl, Br, alkyl, acetyl, C<NUM>-C<NUM> acyl group; R<NUM> is selected from -H, -CH<NUM>OH, -OH, alkyl, alkoxy; R<NUM> is selected from alkyl.

According to an aspect of the present invention, a compound of Formula IV or salts thereof is provided to prevent cell proliferation:
<CHM>
wherein R<NUM> and R<NUM> are each independently selected from -H, -OMe; R is selected from:
<CHM>
wherein, R<NUM> is -OH; R<NUM> is selected from -OMe, -OH; R<NUM> is selected from - OMe, -OH; R<NUM> is -H; R<NUM> is -CH<NUM>; R<NUM> and R<NUM> are each independently selected from -H, or R<NUM> and R<NUM> together form lactone, or -C(O)OC<NUM>H<NUM>; and wherein the compound is selected from:
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>.

In a preferred embodiment of the present invention, a compound of Formula V or salts thereof is provided to prevent cell proliferation:
<CHM>.

The compound of Formula V of the present invention are active on Breast and prostate cancer cell lines. Further, compound of Formula V is potent compared to standard chemotherapeutic drug Cisplatin. The compound of Formula V does not show activity on normal lymphocytes.

In another preferred embodiment of the present invention, a compound of Formula VI or salts thereof is provided to prevent cell proliferation:
<CHM>.

Compound of Formula VI shows activity in breast and prostate cancer cell lines. Further, compound of Formula VI is potent compared to standard chemotherapeutic drug Cisplatin. The compound of Formula VI does not show activity on normal lymphocytes.

In an embodiment, the present invention provides compounds that demonstrate anticancer and anti-cancer stem cell activity particularly in breast and prostate cancer cell lines. In an embodiment, compound of formula VII is provided:
<CHM>
<CHM>.

Compound of Formula VII shows activity in breast and prostate cancer cell lines. The compound of Formula VII does not show activity on normal lymphocytes.

In another embodiment, the present invention provides compound of Formula VIII that prevents cell proliferation.

Compound of Formula VIII shows activity in breast and prostate cancer cell lines and does not show activity on normal lymphocytes.

In a further embodiment of the present invention compound of Formula IX is provided that prevents cell proliferation:
<CHM>
<CHM>.

Compound IX of the present invention shows activity in breast and prostate cancer cell lines.

In yet another embodiment of the present invention, compound of Formula X is provided that prevents cell proliferation:
<CHM>.

Compound of formula X shows activity in breast and prostate cancer cell lines and does not show activity in normal lymphocytes.

In yet another embodiment, the present invention provides compound of Formula XI that prevents cell proliferation:
<CHM>.

Compound of formula XI shows activity in breast and prostate cancer cell lines Also described herein is compound of Formula XII that prevents cell proliferation:
<CHM>.

Compound of formula XII shows activity in breast and prostate cancer cell lines. Further described herein is compound of Formula XIII that prevents cell proliferation:
<CHM>.

Compound of formula XIII shows activity in breast and prostate cancer cell lines.

Additionally described herein is compound of Formula XIV:
<CHM>.

In an aspect of the present invention, compounds of formula V to XI are provided for use in the treatment of cancer. Preferably, the compound of Formula V and VI are provided for use in the treatment of cancer. The cancer can be breast, oral, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, or stomach cancer.

In a preferred embodiment, the compounds of Formula V and VI for use in the treatment of breast and/or prostate cancer is provided.

In a further aspect of the invention, provided are pharmaceutical compositions including the compounds of Formula V to Formula XI, pharmaceutically acceptable excipient including carrier, adjuvant, vehicle or mixtures thereof. Preferably, pharmaceutical compositions including compounds of Formula V and VI pharmaceutically acceptable excipient including carrier, adjuvant, vehicle or mixtures thereof are provided. The pharmaceutical excipient can further include one or more binders, diluents, disintegrants, glidants, lubricants, stabilizers, surface active agents or pH-adjusting agents.

In certain embodiments, the amount of compound in compositions may be such that it is effective to treat cancer in a subject in the need thereof. In certain embodiments, the composition may comprise between the biologically effective dose and the maximum tolerated dose of the compound of the invention or it's pharmaceutically acceptable salt, ester, or salt of an ester.

In certain embodiments, a composition of this invention may be formulated for administration to a subject in the need thereof. The pharmaceutical compositions of the present invention may be formulated into a suitable dosage form to be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. Compositions of the present invention may be formulated into dosage forms including liquid, solid, and semisolid dosage forms. The term "parenteral" as used herein includes subcutaneous, intravenous, intraperitoneal, intramuscular, intra-articular, intrasynovial, intrastemal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intravenously or intraperitoneally.

The present invention also includes the composition including the compounds of the present invention of Formula V to XI, preferably compound of Formula V or VI for use in the treatment of cancer including breast, oral, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, or stomach cancer. In a preferred embodiment, the composition of the present invention is for the treatment of breast, and/or prostate cancer.

In certain embodiments of the present invention disclose a formulation comprising the compounds of the present invention along with other active agents or pharmaceutically acceptable excipients, etc..

In an embodiment, a pharmaceutical composition comprises the aforesaid compounds with another active agent such as but are not limited to imatinib, nilotinib, gefitinib, sunitinib, carfilzomib, salinosporamide A, retinoic acid, cisplatin, carboplatin, oxaliplatin, mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide, azathioprine, mercaptopurine, doxifluridine, fluorouracil, gemcitabine, methotrexate, tioguanine, vincristine, vinblastine, vinorelbine, vindesine, podophyllotoxin, etoposide, teniposide, tafluposide, paclitaxel, docetaxel, irinotecan, topotecan, amsacrine, actinomycin, doxorubicin, daunorubicin, valrubicin, idarubicin, epirubicin, plicamycin, mitomycin, mitoxantrone, melphalan, busulfan, capecitabine, pemetrexed, epothilones, <NUM>-cis-Retinoic Acid, <NUM>-CdA, <NUM>-Chlorodeoxyadenosine, <NUM>-Azacitidine, <NUM>-Fluorouracil, <NUM>-FU, <NUM>-Mercaptopurine, <NUM>-MP, <NUM>-TG, <NUM>-Thioguanine, Abraxane, Accutane, Actinomycin-D, Adriamycin, Adrucil, Afinitor, Agrylin , Ala-Cort, Aldesleukin, Alemtuzumab, ALIMTA, Alitretinoin, Alkaban-AQ, Alkeran, All-transretinoic Acid, Alpha Interferon, Altretamine, Amethopterin, Amifostine, Aminoglutethimide, Anagrelide, Anandron, Anastrozole, Arabinosylcytosine, Ara-C, Aranesp, Aredia, Arimidex, Aromasin, Arranon, Arsenic Trioxide, Arzerra, Asparaginase, ATRA, Avastin, Azacitidine, BCG, BCNU, Bendamustine, Bevacizumab, Bexarotene, BEXXAR, Bicalutamide, BiCNU Aromasin, Blenoxane, Bleomycin, Bortezomib, Busulfan, Busulfex, C225, Calcium Leucovorin, Campath, Camptosar, Camptothecin-<NUM>, Capecitabine, Carac, Carboplatin, Carmustine, Carmustine Wafer, Casodex, CC-<NUM>, CCI-<NUM>, CCNU, CDDP, CeeNU, Cerubidine, Cetuximab, Chlorambucil, Citrovorum Factor, Cladribine, Cortisone, Cosmegen, CPT-<NUM>, Cytadren, Cytosar-U, Cytoxan, Dacarbazine, Dacogen, Dactinomycin, Darbepoetin Alfa, Dasatinib, Daunomycin, Daunorubicin Hydrochloride, Daunorubicin Liposomal, DaunoXome, Decadron, Decitabine, Delta-Cortef, Deltasone, Denileukin, Diftitox, DepoCyt, Dexamethasone, Dexamethasone Acetate, Dexamethasone Sodium Phosphate, Dexasone, Dexrazoxane, DHAD, DIC, Diodex, Docetaxel, Doxil, Doxorubicin, Doxorubicin Liposomal, Droxia, DTIC, DTIC-Dome, Duralone, Efudex, Eligard, Ellence, Eloxatin, Elspar, Emcyt, Epirubicin, Epoetin Alfa, Erbitux, Erlotinib, Erwinia L-asparaginase, Estramustine, Ethyol, Etopophos, Etoposide, Etoposide Phosphate, Eulexin, Everolimus, Evista, Exemestane, Fareston, Faslodex, Femara, Filgrastim, Floxuridine, Fludara, Fludarabine, Fluoroplex, Fluorouracil, Fluorouracil (cream), Fluoxymesterone, Flutamide, Folinic Acid, FUDR, Fulvestrant, G-CSF, Gefitinib, Gemcitabine, Gemtuzumab, ozogamicin, Gemzar Gleevec, Gliadel Wafer, GM-CSF, Goserelin, Granulocyte - Colony Stimulating Factor, Granulocyte Macrophage Colony Stimulating Factor, Halotestin, Herceptin, Hexadrol, Hexalen, Hexamethylmelamine, HMM, Hycamtin, Hydrea, Hydrocort Acetate, Hydrocortisone, Hydrocortisone Sodium Phosphate, Hydrocortisone Sodium Succinate, Hydrocortone Phosphate, Hydroxyurea, Ibritumomab, Tiuxetan, Idamycin, Idarubicin Ifex, IFN-alpha, Ifosfamide, IL-<NUM>, IL-<NUM>, Imatinib mesylate, Imidazole Carboxamide, Interferon alfa, Interferon Alfa-2b (PEG Conjugate), Interleukin-<NUM>, Interleukin-<NUM>, Intron A (interferon alfa-2b), Iressa, Irinotecan, Isotretinoin, Ixabepilone, Ixempra , Kidrolase , Lanacort , Lapatinib, L-asparaginase, LCR, Lenalidomide, Letrozole, Leucovorin, Leukeran, Leukine , Leuprolide, Leurocristine, Leustatin, Liposomal Ara-C, Liquid Pred , Lomustine, L-PAM, L-Sarcolysin, Lupron , Lupron Depot , Matulane , Maxidex, Mechlorethamine, Mechlorethamine Hydrochloride, Medralone , Medrol , Megace , Megestrol, Megestrol Acetate, Melphalan, Mercaptopurine, Mesna, Mesnex , Methotrexate, Methotrexate Sodium, Methylprednisolone, Meticorten , Mitomycin, Mitomycin-C, Mitoxantrone, M-Prednisol , MTC, MTX, Mustargen , Mustine, Mutamycin , Myleran , Mylocel, Mylotarg , Navelbine , Nelarabine, Neosar , Neulasta , Neumega , Neupogen , Nexavar , Nilandron , Nilotinib, Nilutamide, Nipent , Nitrogen Mustard, Novaldex , Novantrone , Nplate, Octreotide, Octreotide acetate, Ofatumumab, Oncospar , Oncovin , Ontak , Onxal, Oprelvekin, Orapred , Orasone , Oxaliplatin, Paclitaxel, Paclitaxel Protein-bound, Pamidronate, Panitumumab, Panretin , Paraplatin , Pazopanib, Pediapred , PEG Interferon, Pegaspargase, Pegfilgrastim, PEG-INTRON , PEG-L-asparaginase, PEMETREXED, Pentostatin, Phenylalanine Mustard, Platinol , Platinol-AQ , Prednisolone, Prednisone, Prelone , Procarbazine, PROCRIT , Proleukin , Prolifeprospan <NUM> with Carmustine Implant, Purinethol , Raloxifene, Revlimid , Rheumatrex , Rituxan , Rituximab, Roferon-A (Interferon Alfa-2a), Romiplostim, Rubex , Rubidomycin hydrochloride, Sandostatin , Sandostatin LAR , Sargramostim, Solu-Cortef , Solu-Medrol , Sorafenib, SPRYCEL , STI-<NUM>, Streptozocin, SU11248, Sunitinib, Sutent, Tamoxifen, Tarceva , Targretin , Tasigna , Taxol , Taxotere , Temodar , Temozolomide, Temsirolimus, Teniposide, TESPA, Thalidomide, Thalomid , TheraCys , Thioguanine, Thioguanine Tabloid , Thiophosphoamide, Thioplex , Thiotepa, TICE , Toposar , Topotecan, Toremifene, Torisel , Tositumomab, Trastuzumab, Treanda , Tretinoin, Trexall , Trisenox , TSPA, TYKERB , VCR, Vectibix , Velban , Velcade , VePesid , Vesanoid , Viadur , Vidaza , Vinblastine, Vinblastine Sulfate, Vincasar Pfs , Vincristine, Vinorelbine, Vinorelbine tartrate, VLB, VM-<NUM>, Vorinostat, Votrient, VP-<NUM>, Vumon , Xeloda , Zanosar , Zevalin , Zinecard , Zoladex , Zoledronic acid, Zolinza, Zometa , or combinations of any of the above.

Also described herein is a method of treating cancer by administering an effective amount of compounds V to XIV. In a preferred example, a method of treating cancer comprising administering an effective amount of compound of formula V or VI is provided. The cancer can be breast, oral, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, or stomach cancer. In a preferred example, the method of treatment comprises administering an effective amount of compound of Formula V or VI can be for the treatment of breast and/ or prostate cancer.

A method of inhibition of unregulated cell growth by administering effective amount of the compounds of the present disclosure is also described herein. Further described herein is a method of treating cancer by administering compounds of the present disclosure along with standard therapies or in combination with other drugs available for the treatment of cancer.

Another example of the disclosure provides for the use of the compounds in the treatment of unregulated cell growth, malaria, dengue.

The foregoing description of the invention has been set merely to illustrate the invention and is not intended to be limiting. Following are the illustrative and non-limiting examples, including the best mode, for practicing the present invention.

Scheme I): i) Br<NUM>, AcOH at room temperature, ii) Ethylene glycol, Toluene, p-Toluenesulphonic acid (PTSA), reflux, iii) n-BuLi, Aldehyde, -<NUM>, iv) Diethylacetylenedicarboxylate (DEADC), methylene dichloride (MDC0, <NUM>, v) LiAlH<NUM>, Tetrahydrofuran (THF).

Synthesis of <NUM>: Substituted aromatic aldehyde (<NUM> mole) was taken in AcOH (<NUM>) and Br<NUM> (<NUM> mole) was added slowly from addition funnel. The mixture was stirred for <NUM> at room temperature and then poured over ice (<NUM>) and stirred vigorously for <NUM>. Slurry was filtered and residue was washed with cold methanol and suction dried under vacuum to obtain pure product <NUM>. Yield, <NUM> mole (<NUM>%).

Synthesis of <NUM>: Compound <NUM> (<NUM>. 11mole) was dispersed in <NUM> of toluene. Ethylene glycol <NUM> and p-Toluenesulphonic acid (<NUM>) were added and mixture was refluxed using Dean-stark assembly for <NUM>. Reaction was monitored with TLC (<NUM>:<NUM>, Ethyl acetate:Hexane). After completion of reaction, saturated NaHCO<NUM> solution was added into the reaction and layers were separated. Toluene layer was washed with brine and dried over anhydrous Na2SO4. Dried toluene layer was evaporated in vacuum to afford pure product <NUM> (<NUM>. 11mole, <NUM>%).

Synthesis of <NUM>: In an inert reaction assembly charged with nitrogen compound <NUM> (<NUM> mole) was dissolved in Dry THF (<NUM>). Mixture was then cooled in a dry ice/acetone bath till -<NUM>. Through transfer needle <NUM> n-BuLi (<NUM> solution in hexane) was added carefully and slowly into the above solution over <NUM>. Mixture was stirred for <NUM> at -<NUM>. In a separate addition funnel, the solution of R<NUM>-CHO in THF was added drop wise in to the lithiated solution at - <NUM>. Mixture was stirred for <NUM> at same temperature and left at room temperature for <NUM>. Mixture was quenched with <NUM> sat. NH<NUM>Cl solution and extracted with ethyl acetate (<NUM> x <NUM>). Ethyl acetate layer was washed with brine solution (100mLx <NUM>), dried over anhydrous Na<NUM>SO<NUM> and evaporated in vacuum to isolate crude product. Purification by column chromatography (in silica gel, Ethyl acetate: hexane) gave pure product <NUM> (<NUM>. 008mole, <NUM>%).

Synthesis of <NUM>: Compound <NUM> (<NUM> mole), acetic acid (<NUM>), DEADC (<NUM> mole) and MDC (<NUM>) were taken into the high pressure closed vessel. Mixture was heated at <NUM> for <NUM>. Heating stopped and mixture was washed with saturated NaHCO<NUM>. MDC layer was dried with anhydrous Na<NUM>SO<NUM> and solvents were evaporated in vacuum and crude product was purified by silica gel column chromatography in ethyl acetate: hexane as a mobile phase. Pure product <NUM> obtained as an off white solid (<NUM> mole, <NUM>%).

Synthesis of <NUM>: Ester <NUM> (<NUM> mole) was dissolved in dry THF and slowly added into the dispersion of LiAlH<NUM> (<NUM> mole) in THF at <NUM>. Mixture was stirred at <NUM> for <NUM> and then at room temperature for overnight. Reaction was quenched with saturated NH<NUM>Cl and product was extracted with MDC. Crude product was purified by column chromatography to obtain pure product <NUM> (<NUM> mole).

Synthesis of tetra-acylated d-xylose (<NUM>): D-xylose (<NUM>. 13mole) was mixed in MDC (<NUM>) and pyridine at room temperature. Mixture cooled to <NUM> and acetyl chloride (<NUM> mole) was added slowly under vigorous stirring. Mixture stirred for <NUM> at <NUM>° and then at room temperature for <NUM>. 50gm crushed ice was added into the mixture and then <NUM> MDC. Layers were separated and MDC extract was washed with brine solution (<NUM> x <NUM>) and <NUM>% aq. CuSO<NUM> solution until original CuSO4 solution color persists. MDC layer was dried over anhydrous Na<NUM>SO<NUM> and evaporated in vacuum on rotary evaporator to obtain the syrupy product <NUM> (<NUM> mole, <NUM>%).

Synthesis of <NUM>: In a clean and dry round bottom flask, with nitrogen inlet, compound <NUM> (<NUM> mole) was dissolved in <NUM> dry MDC. Mixture cooled to <NUM> in an ice bath and <NUM> HBr/AcOH (<NUM>% solution) was added drop wise over a period of <NUM>. Material stirred for <NUM> at <NUM> and quenched with <NUM> ice and stirred for <NUM>. MDC layer was separated and washed with sat. NaHCO<NUM> (<NUM> x <NUM>), brine (<NUM>) and dried over anhydrous Na<NUM>SO<NUM> and evaporated in vacuum on rotary evaporator to obtain the off-white solid product <NUM> (<NUM>. 097mole, <NUM>%).

Synthesis of <NUM>: Above compound <NUM> was taken directly into another round bottom flask containing TBAB (<NUM> mole), <NUM>, <NUM>-Lutidine (<NUM> mole) and MDC <NUM> and stirred at room temperature for <NUM>. After <NUM> stirring <NUM> EtOH was added slowly and stirring continued for overnight. Solvent removed on rotary evaporator and residue triturated in ethyl acetate (<NUM>). Solids were removed by filtration and filtrate was evaporated. Syrupy crude product was purified by silica gel column chromatography in ethyl acetate: hexane to obtain semisolid pure product <NUM> (<NUM> mole, <NUM>%).

Synthesis of <NUM>: In a single neck round bottom flask compound <NUM> (<NUM> mole) was dissolved in MeOH at room temperature. This mixture cooled between <NUM>-<NUM> and NaOMe (<NUM>) was added in small portions over <NUM> and then stirred for <NUM> at room temperature. Thin Later Chromatography (TLC) confirmed the de-acylated product formation. Methanol evaporated on rotary evaporator and residue was dissolved in dry DMF (<NUM>). DMF solution chilled to <NUM> and NaH (<NUM>, <NUM>% suspension) was added portion wise under vigorous stirring under nitrogen atmosphere. Suspension stirred for <NUM> at same temperature and methyl iodide was added slowly. Whole suspension was stirred overnight at RT. When TLC confirmed the product formation, <NUM> MeOH and crushed ice, (<NUM>) were added slowly. Reaction mixture was extracted with ethyl acetate (<NUM> x <NUM>). Combined ethyl acetate extract was washed with saturated brine solution (<NUM> x <NUM>) dried over an. Na2SO4 and evaporated on rotary evaporator to obtain oily liquid product <NUM> (<NUM> mole, <NUM>%).

Synthesis of <NUM>: Compound <NUM> (<NUM> mole) was dissolved in gl. AcOH (<NUM>) at <NUM> and stirred for <NUM> at room temperature. Acetic acid was evaporated and obtained syrupy residue was dissolved in pyridine (<NUM>) and cooled up to <NUM>. Ac-Cl was slowly charged into the chilled solution and stirred at room temperature for overnight. Into the reaction mixture <NUM> chilled water was added and extracted with diethyl ether (<NUM> x <NUM>). Ether extract was washed with sat. CuSO<NUM> solution (<NUM> x4) and brine (<NUM>) dried over An. Na<NUM>SO<NUM> and evaporated on rotary evaporator to isolate product <NUM> (<NUM>. 038mole, <NUM>%).

Synthesis of <NUM>: In <NUM> dry MDC <NUM> (<NUM> mole) was added and chilled upto <NUM>. <NUM> HBr/AcOH (<NUM>% solution) was added slowly and mixture was stirred for <NUM> at <NUM>. Crushed ice (<NUM>) was added in to the reaction stirred for <NUM>. MDC layer was washed with sat. NaHCO<NUM> solution (<NUM> x <NUM>), brine (<NUM>) and dried over Na<NUM>SO<NUM> and resulting solution used as such for the synthesis of <NUM> (see scheme III).

Synthesis of <NUM>: Diphyllin derivative (<NUM>, <NUM> mole), TBAB (<NUM> mole) and 2N NaOH (<NUM>) were mixed in MDC (<NUM>) at <NUM>. To this, above prepared solution of <NUM> in MDC was added slowly. Reaction was stirred for <NUM> and TLC confirmed the product formation. Into the reaction, <NUM> ice cold water was added and stirred vigorously, and then organic phase was separated. MDC layer was washed with 2N NaOH, water, brine and dried over Na<NUM>SO<NUM>, evaporated on rotary evaporator to obtain crude <NUM> (<NUM>). Crude product was purified by silica gel column chromatography in Ethyl acetate: Hexane from which pure compound <NUM> (<NUM>. 0020mole) was isolated.

Synthesis of <NUM>: Condensation product <NUM> (<NUM> mole) from Glycoside and diphyllin derivative was dissolved in MeOH and chilled the solution till <NUM>°. To this solution anhydrous K<NUM>CO<NUM> was added and stirred for <NUM> at room temperature. TLC shows complete conversion of <NUM> into the product <NUM>. HCl (1N) was added to adjust the neutral pH and MDC was added to extract the product. MDC layer was washed with brine and dried over Na<NUM>SO<NUM> and evaporation of MDC on rotary evaporator afforded crude product, which was purified by silica gel column chromatography in Ethyl acetate: Hexane. Pure product <NUM> (<NUM> mole, <NUM>%) was obtained with ><NUM>% purity.

Reagents and conditions: a) NBS (N-Bromosuccinimide), ACN (Acetonitrile, RT, <NUM> hr; b) PhCH<NUM>Br, K<NUM>CO<NUM>, DMF (Dimethylformamide); c) Pd(PPh<NUM>)<NUM>, <NUM>,<NUM>-(methylenedioxy) phenylboronic acid, Na<NUM>CO<NUM>, DME (Dimethoxyethane); d) <NUM>% Pd/C, EtOH:EtOAc (<NUM>:<NUM>), <NUM>, <NUM>-<NUM> psi.

To a solution of <NUM> (<NUM>, <NUM> mmol) in <NUM> of ACN, NBS (<NUM>, <NUM> mmol) was added over a period of <NUM> hr. The reaction mixture was stirred at RT for additional <NUM> and monitored using TLC. The solvent was evaporated and the residue was partitioned I;n diethyl ether and water. The ethereal layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

To a solution of <NUM> (<NUM>, <NUM> mmol) in DMF, K<NUM>CO<NUM> (<NUM>, <NUM> mmol) was added followed by slow addition of benzyl bromide (<NUM>, <NUM> mmol). The reaction mixture was stirred at RT and monitored using TLC. After completion, reaction was quenched with brine and the residue was extracted using ethyl acetate and washed with water. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained solid was purified by column chromatography (Hex: EtOAc, <NUM>:<NUM>).

To a solution of <NUM> (<NUM>, <NUM> mmol) in DME, Pd(PPh<NUM>)<NUM> (<NUM>, <NUM> mol %) was added and stirred for <NUM> at RT. The suspension of <NUM>,<NUM>-(methylenedioxy) phenylboronic acid (<NUM>, <NUM> mmol) in DME was added to the above solution followed by addition of <NUM> Na<NUM>CO<NUM> (<NUM>) solution. The reaction mixture was refluxed overnight, and monitored using TLC after completion, cooled to RT and solvent was distilled off. The residue was treated with aq. NH<NUM>Cl solution and extracted in ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained solid was purified by column chromatography (Hexane: DCM, <NUM>:<NUM>).

A mixture of <NUM> (<NUM>, <NUM> mmol), <NUM>% Pd/C in <NUM> of mixture of EtOH: EtOAc (<NUM>: <NUM>) was placed in shaker hydrogenation apparatus at <NUM> and <NUM>-<NUM> psi. The reaction was monitored using TLC. After completion, Pd/C was filtered off and the filtrate was evaporated. The obtained solid was purified by column chromatography (DCM: MeOH, <NUM>:<NUM>).

Reagents and conditions: a) Ac<NUM>O, pyridine; b) HBr•AcOH, DCM (Dichloromethane); c) <NUM>,<NUM>-lutidine, Bu<NUM>NBr, EtOH, DCM; d) <NUM>. MeONa, MeOH; <NUM>. NaH, MeI, DMF (Dimethylformamide); e) AcOH, Ac<NUM>O, Pyridine; f) HBr•AcOH, DCM.

To a <NUM>-mL three-neck RBF equipped with guard-tube and stopper, were added <NUM> (<NUM>, <NUM> mol), pyridine (<NUM>) and cooled at <NUM>. Acetic anhydride (<NUM>) was added dropwise to the above mixture at <NUM>. The resulting reaction mixture was stirred at <NUM> for <NUM>. After consumption of starting materials, as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was poured into ice water (<NUM>) and ether was added (<NUM>). Organic layer was separated, and aqueous layer was extracted with ether (<NUM> x <NUM>). Organic layers were combined and washed with saturated cupric salt solution till free from pyridine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give sticky solid compound <NUM>.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J = <NUM>), <NUM> (t, <NUM>, J = <NUM>), <NUM> (m, <NUM>), <NUM> (dd, <NUM>, J =<NUM>, <NUM><NUM>), <NUM> (t, <NUM>, J = <NUM><NUM>), <NUM> (s, <NUM>), <NUM>(s, <NUM>), <NUM> (s, <NUM>).

<NUM>-RBF with guard tube was charged with <NUM> (<NUM>, <NUM> mol) and dichloromethane (<NUM>) and the mixture was cooled to <NUM> in ice bath. To the above cold solution was added hydrogen bromide (<NUM> % in acetic acid; <NUM>) with constant stirring during <NUM> and reaction mixture was further stirred at room temperature for <NUM>. After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was washed with ice water (<NUM> x <NUM>), <NUM> % NaHCO<NUM> solution (<NUM> x <NUM>), <NUM> % NaHCO<NUM> solution (<NUM> x <NUM>) and finally by brine solution (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtained white solid of <NUM>.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J= <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM>- <NUM> (m, <NUM>), <NUM> (dd, <NUM>, J= <NUM>, <NUM>), <NUM> (dd, <NUM>, J= <NUM>, <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>).

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J = <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (dd, <NUM> J= <NUM>, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (t, <NUM>, <NUM>).

<NUM> (<NUM>, <NUM> mmol) was dissolved in acetic acid (<NUM>) and resulting solution was stirred at <NUM> for <NUM>. Reaction mixture was concentrated under reduced pressure and the residue was treated with acetic anhydride (<NUM>) and pyridine (<NUM>). The resulting solution was maintained at room temperature with stirring for overnight. After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was poured into cold water (<NUM>) and extracted with ether (<NUM> x <NUM>). The organic layers were combined, washed with saturated cupric sulfate solution till the pyridine was removed and then dried over anhydrous sodium sulfate. The inorganic solids were filtered off, filtrate was concentrated under reduced pressure and residue was purified by column chromatography over silica gel using EtOAc: Hexane (<NUM>:<NUM>) as eluent to afford <NUM> as a light yellow color.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J= <NUM>), <NUM> (t, <NUM> J= <NUM>), <NUM><NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM>(s, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM>(s, <NUM>), <NUM>(s, <NUM>).

In a clean and dry <NUM> RBF, <NUM> (<NUM>, <NUM> mmol) was dissolved in dichloromethane (<NUM>) and cooled to <NUM> in ice bath. To the above cooled solution was added hydrogen bromide in AcOH (<NUM>% solution; <NUM>) with constant stirring for <NUM> and further stirred at room temperature for another <NUM>.

After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was diluted with dichloromethane (<NUM>), washed with ice water (<NUM>) followed by saturated NaHCO<NUM> solution (<NUM>) and finally with brine solution (<NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give yellow colored liquid <NUM> as a product.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J= <NUM>), <NUM> (dd, <NUM>, J= <NUM>, <NUM>), <NUM> (dd, <NUM>, J = <NUM>, <NUM><NUM>. Hz), <NUM> (m, <NUM>), <NUM>(s, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>).

Reagents and conditions: a) Bu<NUM>NBr, <NUM> NaOH, DCM (Dichloromethane), RT; b) K<NUM>CO<NUM> MeOH, RT. b) K<NUM>CO<NUM> MeOH, RT.

To a <NUM> RBF, <NUM> (<NUM>, <NUM> mmol), <NUM> (<NUM>, <NUM> mmol) and tetrabutyl ammonium bromide (<NUM>, <NUM> mmol) were taken in dichloromethane (<NUM>) with stirring. To this suspension was added <NUM> NaOH (<NUM>) solution and stirring was continued for <NUM> at room temperature. After the completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: DCM), the reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). The combined organic layer was washed with <NUM>% NaOH solution (<NUM> x <NUM>) followed by water (<NUM> x <NUM>) and dried over anhydrous sodium sulfate. Inorganic salts were filtered off; filtrate was concentrated under reduced pressure and crude mass which was purified by column chromatography using EtOAc: dichloromethane (<NUM>:<NUM>) as eluent to obtain <NUM> as white solid.

To a solution of <NUM> (<NUM>, <NUM> mmol) in methanol (<NUM>) was added solid anhydrous K<NUM>CO<NUM> (<NUM> <NUM> mmol) and reaction mixture was stirred at room temperature for <NUM>. After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), methanol was removed under reduced pressure, water was added and extracted with CH<NUM>Cl<NUM> (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to get <NUM> as white fluffy solid. % Purity: <NUM>%; LC-MS (ESI) m/z: <NUM> [M+H]+.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (dd, <NUM>, J = <NUM>, <NUM><NUM>. Hz), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>).

Reagents and conditions: a) Bu<NUM>NBr, <NUM> NaOH, DCM (Dichloromethane), RT; b) K<NUM>CO<NUM>, MeOH, RT.

To a <NUM>-mL round bottom flask, diethyl <NUM>-(benzo[d][<NUM>,<NUM>]dioxol-<NUM>-yl)-<NUM>-hydroxy-<NUM>,<NUM>-dimethoxynaphthalene-<NUM>,<NUM>-dicarboxylate (<NUM>; <NUM>, <NUM> mmole), <NUM>-O-Acetyl-<NUM>,<NUM>-dimethoxy-α-D-bromoxylopyranose (<NUM>, <NUM>, <NUM> mmole) and tetrabutyl ammonium bromide (<NUM>, <NUM> mmole) were taken in dichloromethane (<NUM>) with stirring. To this suspension was added <NUM> NaOH (<NUM>) solution and stirring was continued for <NUM> at room temperature. After the completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc:DCM), the reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). The combined organic layer was washed with <NUM>% NaOH solution (<NUM> x <NUM>) followed by water (<NUM> x <NUM>) and dried over anhydrous sodium sulfate. Inorganic salts were filtered off, filtrate was concentrated under reduced pressure and crude mass which was purified by column chromatography <NUM> using EtOAc: dichloromethane (<NUM>:<NUM>) as eluent to obtain Cleyacetate (<NUM>) as an oil.

To a solution of <NUM> (<NUM> , <NUM> mmole) in methanol (<NUM>) was added solid anhydrous K<NUM>CO<NUM> (<NUM> <NUM> mmol) and reaction mixture was stirred at room temperature for <NUM>. After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc:Hexane), methanol was removed under reduced pressure, water was added and extracted with CH<NUM>Cl<NUM> (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to get <NUM> as off white fluffy solid.

Yield: <NUM> (<NUM>%); % Purity: <NUM>%; LC-MS (ESI) m/z: <NUM> [M+H]+.

<NUM>HNMR (CDCl3, <NUM>): □ = <NUM> (s, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (dd, <NUM>, J = <NUM>, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> ( s, <NUM>), <NUM> (m, <NUM>), <NUM> (q, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (t, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (s, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>).

Reagents and conditions: a) Br2, AcOH, <NUM>; b) ethylene glycol, p-TSA (toluene sulfonic acid), toluene; c) n-BuLi, THF (tetrahydrofuran); d) piperinol, THF; e) diethyl acetylinedicarboxylate, AcOH, DCM; f) LiAlH<NUM>, THF.

Three necked RBF (<NUM>) equipped with dropping funnel, magnetic stirrer, and stopper was charged with veratraldehyde or <NUM>,<NUM>-dimethoxybenzaldehyde (<NUM>, <NUM>, <NUM> mol) and acetic acid (<NUM>). To this solution was added bromine (<NUM>) in acetic acid (<NUM>) dropwise with constant stirring over half an hour and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Water (<NUM>) was added to the reaction mixture and cooled to <NUM>. The precipitated solid was filtered off, washed with cold water and dried under vacuum to get a white solid <NUM>.

<NUM>H-NMR (CDC13, <NUM>): δ = <NUM> (s, <NUM>), <NUM> (s, IH), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>).

Three necked RBF (<NUM>) was equipped with Dean-Stark apparatus and reflux condenser, was charged with <NUM> (<NUM>, <NUM> mol), toluene (<NUM>), ethylene glycol (<NUM>, <NUM> mol) and catalytic amount of p-toluene sulphonic acid. The reaction flask was immersed in oil bath and heated (<NUM>-<NUM>) under reflux for <NUM> (till all the water removed). After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was allowed to cool to room temperature, neutralized by sodium bicarbonate solution and extracted with ethyl acetate (<NUM> x <NUM>). All the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid. <NUM>H-NMR (<NUM>, CDCl3): δ = <NUM><NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM>(s, <NUM>), <NUM> (t, <NUM>, J = <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>).

To a flame dried three necked RBF (<NUM>) were added <NUM> (<NUM>, <NUM> mole) and anhydrous THF (<NUM>) under nitrogen atmosphere. The flask was cooling to -<NUM> in dry ice-acetone bath, n-BuLi (<NUM>, <NUM> mol) was added dropwise with stirring at -<NUM> and stirred for <NUM>. A separate flame dried flask was charged with piperonal (<NUM>, <NUM> mol) and dry THF (<NUM>). The piperonal solution was cannulated to the reaction mixture during <NUM> and after the addition; reaction mixture was slowly warmed to room temperature and further stirred for <NUM>. After the consumption of all bromo compound, as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was quenched by the addition of saturated ammonium chloride solution and extracted with ethyl acetate (<NUM> x <NUM>). All the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by titration with heptane and <NUM> is sufficiently pure to proceed to next step.

<NUM>H-NMR (<NUM>, CDCl3): δ = <NUM> (s, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM><NUM> (s, <NUM> ), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM> ). 13C-NMR (<NUM>, CDCl<NUM>): δ = <NUM>, <NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM><NUM>, <NUM><NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>.

Sealed tube was charged with <NUM> (<NUM>, <NUM> mmol), diethyl acetylinedicarboxylate (<NUM>, <NUM> mol), dichloromethane (<NUM>) and glacial acetic acid (<NUM>) and mixture was heated at <NUM> for <NUM>. After completion of reaction as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was cooled to room temperature, diluted with dichloromethane (<NUM>), washed with <NUM> % sodium bicarbonate solution (<NUM> x <NUM>), organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude reaction mass was purified by flash column chromatography over silica gel using EtOAc: Hexane (<NUM>:<NUM>) to afford <NUM> as white solid.

<NUM>H-NMR (<NUM>, CDCl<NUM>): δ = <NUM> (s,<NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (q, <NUM>, J= <NUM>), <NUM> (q, <NUM>, J =<NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (t, <NUM>, J= <NUM>). 13C-NMR (<NUM>, CDCl<NUM>): δ = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM><NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>.

Two necked RBF (<NUM>) was charged with LAH (<NUM>, <NUM> mmol) and anhydrous THF (<NUM>) and the mixture was cooled to <NUM> with stirring. To this suspension, a solution of <NUM> (<NUM>, <NUM> mmol) in THF (<NUM>) was added dropwise at <NUM> and stirring was continued for <NUM> at same temperature. After completion of reaction as judged by TLC (<NUM>:<NUM>, MeOH: DCM), reaction mixture was quenched with saturated sodium sulfate solution and extracted with t-butanol (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel to give yellow solid <NUM>.

<NUM>H-NMR (<NUM>, DMSOd6) δ = <NUM> (s, <NUM>), <NUM> (s, I H), <NUM> (d, <NUM>, J= <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (dd, <NUM> J= <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). 13C-NMR (<NUM>, DMSOd6): δ = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM><NUM>, <NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>.

To a <NUM> RBF, <NUM> (<NUM> eq. ), corresponding carboxylic acid (<NUM> eq. ), DMAP (<NUM> eq. ) in <NUM> of DCM was cooled (at <NUM>). The reaction mixture was stirred for <NUM>. and then DCC (<NUM> eq. dissolved in cold DCM) was added dropwise.

The reaction was stirred at RT overnight. The reaction was monitored using TLC (<NUM>:<NUM>, MeOH: DCM). After completion, the solid obtained was filtered off and the filtrate was diluted with DCM and washed with water twice. The combined organic layer was dried over Na<NUM>SO<NUM> and concentrated under reduced pressure.

The obtained solid was purified by column chromatography (DCM: MeOH, <NUM>:<NUM>).

Reagents and conditions: a) <NUM>-methyl-<NUM>-pyrrolecarboxylic acid, DMAP (<NUM>-Dimethylaminopyridine), DCC (N,N'-Dicyclohexylcarbodiimide), DCM (Dichloromethane), <NUM> overnight.

To a <NUM> RBF, Diphyllin (<NUM>, <NUM> mmol), <NUM>-methyl-<NUM>-pyrrole-<NUM>-carboxylic acid (<NUM>, <NUM> mmol), DMAP (<NUM>, <NUM> mmol) in <NUM> of DCM was cooled (at <NUM>). The reaction mixture was stirred for <NUM>. and then DCC (<NUM>, <NUM> mmol dissolved in cold DCM) was added dropwise.

The reaction was stirred at RT overnight. The reaction was monitored using TLC (<NUM>:<NUM>, DCM:MeOH). After completion, the solid obtained was filtered off and the filtrate was diluted with DCM and washed with water twice. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure.

The obtained solid was purified by column chromatography (DCM:MeOH, <NUM>:<NUM>). % Purity: <NUM>%; LC-MS (ESI) m/z: <NUM> [M+H]+.

<NUM>H-NMR (<NUM>, CDCl3): δ = <NUM> - <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>).

Reagents and conditions: a) α-phenylcyclopentaneacetic acid, DMAP (<NUM>-Dimethylaminopyridine), DCC (N,N'-Dicyclohexylcarbodiimide), DCM (Dichloromethane), <NUM> overnight.

To a <NUM> RBF, Diphyllin (<NUM>, <NUM> mmol), <NUM>-cyclopentyl-<NUM>-phenylacetic acid (<NUM>, <NUM> mmol), DMAP (<NUM>, <NUM> mmol) in <NUM> of DCM was cooled (at <NUM>). The reaction mixture was stirred for <NUM>. and then DCC (<NUM>, <NUM> mmol dissolved in cold DCM) was added dropwise. The reaction was stirred at RT overnight. The reaction was monitored using TLC (<NUM>:<NUM>, DCM:MeOH). After completion, the solid obtained was filtered off and the filtrate was diluted with DCM and washed with water twice. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained solid was purified by column chromatography (DCM:MeOH, <NUM>:<NUM>). % Purity: <NUM>%; LC-MS (ESI) m/z: <NUM> [M+H]+.

<NUM>H-NMR (<NUM>, CDCl3): δ = <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>).

To a <NUM> RBF, <NUM> (<NUM>, <NUM> mmol), <NUM>-methyl-<NUM>-pyrrole-<NUM>-carboxylic acid (<NUM>, <NUM> mmol), DMAP (<NUM>, <NUM> mmol) in <NUM> of DCM was cooled (at <NUM>). The reaction mixture was stirred for <NUM>. and then DCC (<NUM>, <NUM> mmol, dissolved in cold DCM) was added dropwise. The reaction was stirred at RT overnight. The reaction was monitored using TLC (<NUM>:<NUM>, DCM:MeOH). After completion, the solid obtained was filtered off and the filtrate was diluted with DCM and washed with water twice. The combined organic layer was dried over Na<NUM>SO<NUM> and concentrated under reduced pressure.

<NUM>H NMR (<NUM>, CDCl3) δ: <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>).

Reagents and conditions: a) <NUM>-methyl-<NUM>-pyrrolecarboxylic acid, DMAP, DCC, DCM, <NUM> overnight.

Synthesis <NUM>-(benzo[d][<NUM>,<NUM>]dioxol-<NUM>-yl)naphthalen-<NUM>-yl <NUM>-methyl-<NUM>-pyrrole-<NUM>-carboxylate ( <NUM>): To a <NUM> RBF, <NUM> (<NUM>, <NUM> mmol), <NUM>-cyclopentyl-<NUM>-phenylacetic acid (<NUM>, <NUM> mmol), DMAP (<NUM>, <NUM> mmol) in <NUM> of DCM was cooled (at <NUM>). The reaction mixture was stirred for <NUM>. and then DCC (<NUM>, <NUM> mmol, dissolved in cold DCM) was added dropwise. The reaction was stirred at RT overnight. The reaction was monitored using TLC (<NUM>:<NUM>, DCM:MeOH). After completion, the solid obtained was filtered off and the filtrate was diluted with DCM and washed with water twice. The combined organic layer was dried over Na<NUM>SO<NUM> and concentrated under reduced pressure. The obtained solid was purified by column chromatography (DCM:MeOH, <NUM>:<NUM>).

<NUM>H NMR (<NUM>, CDCl<NUM>) δ: <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). % Purity: <NUM>%; LC-MS (ESI) m/z: <NUM> [M+H]+.

To a <NUM>-mL three-neck RBF equipped with guard-tube and stopper, were added <NUM> (<NUM>, <NUM> mol), pyridine (<NUM>) and cooled it at <NUM>. Acetic anhydride (<NUM>) was added dropwise to the above mixture at <NUM>. The resulting reaction mixture was stirred at <NUM> for <NUM> After consumption of starting materials, as judged by TLC (<NUM>:<NUM>, EtOAc: Hexane), reaction mixture was poured into ice water (<NUM>) and ether was added (<NUM>). Organic layer was separated and aqueous layer was extracted with ether (<NUM> x <NUM>).

Organic layers were combined and washed with saturated cupric salt solution till free from pyridine. The organic layer was dried over anhydrous sodium sulfate,.

filtered and concentrated to give sticky solid compound <NUM>.

<NUM>H-NMR (<NUM>, CDCl3): δ = <NUM> (d, <NUM>, J = <NUM>), <NUM> (t, <NUM>, J = <NUM>), <NUM> (m, <NUM>), <NUM> (dd, <NUM>, J =<NUM>, <NUM><NUM>), <NUM> (t, <NUM>, J = <NUM><NUM>), <NUM> (s, <NUM>), <NUM>(s, <NUM>), <NUM> (s, <NUM>).

Reagents and conditions: a) Bu<NUM>NBr, <NUM> NaOH, DCM (Dichloromethane), RT; b) K<NUM>CO<NUM> MeOH, RT.

To a <NUM> RBF, <NUM> (<NUM>, <NUM> mmol), <NUM> (<NUM>, <NUM> mmol) and tetrabutyl ammonium bromide (<NUM>, <NUM> mmol) were taken in dichloromethane (<NUM>) with stirring. To this suspension was added <NUM> NaOH (<NUM>) solution and stirring was continued for <NUM> at room temperature. After the completion of reaction as judged by TLC (<NUM> : <NUM>, EtOAc: Hexane), the reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). The combined organic layer washed with <NUM>% NaOH solution (<NUM> x <NUM>) followed by water (<NUM> x <NUM>) and dried over anhydrous sodium sulfate. Inorganic salts were filtered off; filtrate was concentrated under reduced pressure and crude mass which was purified by column chromatography using EtOAc: Hexane (<NUM>:<NUM>) as eluent to <NUM> as white solid.

To a solution of <NUM> (<NUM>, <NUM> mmol) in methanol (<NUM>) was added solid anhydrous K<NUM>CO<NUM> (<NUM> <NUM> mmol) and reaction mixture was stirred at room temperature for <NUM>. After completion of reaction as judged by TLC (<NUM>:<NUM>, MeOH : EtOAc), methanol was removed under reduced pressure, water was added and extracted with CH<NUM>Cl<NUM> (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to get <NUM> as white fluffy solid.

<NUM>H-NMR (<NUM>, CDCl3): δ = <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (d, <NUM>, J = <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>).

Reagents and conditions: a) NBS, DCM, <NUM>, 1hr; b) Tetrakis palladium (<NUM>), Na<NUM>CO<NUM>, H<NUM>O, DME (Dimethoxyethane), reflux, <NUM> hrs; c) furan-<NUM>-carbonyl chloride, Triethylamine, DCM, rt, <NUM> hrs.

Single neck RBF (<NUM>) equipped with magnetic stirrer and guard tube was charged with naphthylamine (<NUM>, <NUM>, <NUM> mol) and DCM (<NUM>). To this solution was added N-Bromosuccinimide (<NUM> gm, <NUM> mol) portionwise with constant stirring over half an hour at <NUM>. and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in cold water (<NUM>). The reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

Single necked RBF (<NUM>) equipped with magnetic stirrer, condenser and guard tube was charged with <NUM>-bromonaphthalen-<NUM>-amine (<NUM>, <NUM>, <NUM> mmol) and <NUM>, <NUM> (methylenedioxy) phenylboronic acid (<NUM> gm, <NUM> mmol) in DME (<NUM>). To this solution was added sodium carbonate (<NUM> gm, <NUM> mmol) dissolved in water (<NUM>). Reaction mixture was stirred at rt for <NUM> minutes and then added tetrakis palladium (<NUM>) (<NUM> gm, <NUM> mmol). Reaction mixture was refluxed for <NUM> hrs. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in water (<NUM>). The reaction mixture was extracted with ethyl acetate (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

Single neck RBF (<NUM>) equipped with magnetic stirrer and guard tube was charged with <NUM>-(benzo[d][<NUM>,<NUM>]dioxol-<NUM>-yl)naphthalen-<NUM>-amine (<NUM>, <NUM>, <NUM> mmol), trimethylamine (<NUM>, <NUM> mmol) and DCM (<NUM>). To this solution was added furan-<NUM>-carbonyl chloride (<NUM>, <NUM> mmol) dropwise with constant stirring over half an hour at <NUM>. and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in cold water (<NUM>). The reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

<NUM>H-NMR (<NUM>, DMSO): δ = <NUM> (s, <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (t, <NUM>, J= <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>).

Reagents and conditions: a) K<NUM>CO<NUM>, DMF (Dimethylformamide), RT, <NUM> hrs; b) NBS, DCM, <NUM>, 1hr; c) Tetrakis palladium (<NUM>), Na<NUM>CO<NUM>, H<NUM>O, DME (Dimethoxyethane), reflux, <NUM> hrs; d) MeOH. HCl, RT, <NUM> hrs.

Three necked RBF (<NUM>) equipped with dropping funnel, magnetic stirrer, and guard tube was charged with <NUM>-Hydroxyquinolin (<NUM>, <NUM>, <NUM> mol), potassium carbonate (<NUM> gm, <NUM> mol) and DMF (<NUM>). To this solution was added benzylbromide (<NUM>, <NUM> mol) dropwise with constant stirring over half an hour and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in cold water (<NUM>). The reaction mixture was extracted with ethyl acetate (<NUM> x <NUM>). All the organic layer combine and washed with water (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

Single necked RBF (<NUM>) equipped with magnetic stirrer, and guard tube was charged with <NUM>-benzyloxyquinolin (<NUM>, <NUM>, <NUM> mol) in DCM (<NUM>). To this solution was added N-Bromosuccinimide (<NUM> gm, <NUM> mol) portiowise with constant stirring over half an hour at <NUM> and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in cold water (<NUM>). The reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

Single necked RBF (<NUM>) equipped with magnetic stirrer, condenser and guard tube was charged with <NUM>-(benzyloxy)-<NUM>-bromoquinoline (<NUM>, <NUM>, <NUM> mol) and <NUM>, <NUM> (methylenedioxy) phenylboronic acid (<NUM> gm, <NUM> mol) in DME (<NUM>). To this solution was added sodium carbonate (<NUM> gm, <NUM> mol) dissolved in water (<NUM>). Reaction mixture was stirred at rt for <NUM> minutes and then added tetrakis palladium (<NUM>) (<NUM> gm, <NUM> mol). Reaction mixture was refluxed for <NUM> hrs. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in water (<NUM>). The reaction mixture was extracted with ethyl acetate (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

Single necked RBF (<NUM>) equipped with magnetic stirrer and guard tube was charged with <NUM>-(benzo[d][<NUM>,<NUM>]dioxol-<NUM>-yl)-<NUM>-(benzyloxy)quinoline (<NUM>, <NUM>) in dry DCM (<NUM>). To this solution was added methanolic HCl at <NUM>. Reaction mixture was stirred for <NUM> hrs at <NUM>. Reaction mixture was monitored with TLC. The reaction mixture was concentrated under reduced pressure. The crude compound was crystalized using ethyl acetate and pet ether to afford <NUM> as a white solid (Yield = <NUM> gm).

<NUM>H-NMR (<NUM>, DMSO): δ = <NUM><NUM> (d, <NUM>, J= <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>).

Reagents and conditions: a) Triethylamine, DCM, <NUM>, 1hr, RT for <NUM> hr.

Single neck RBF (<NUM>) equipped with magnetic stirrer and guard tube was charged with <NUM>-phenylnaphthalen-<NUM>-amine (<NUM>, <NUM>, <NUM> mmol), trimethylamine (<NUM>, <NUM> mmol) and DCM (<NUM>). To this solution was added methane sulphonyl chloride (<NUM>, <NUM> mmol) dropwise with constant stirring over half an hour at <NUM>. and stirring was further continued for <NUM> at room temperature. During this time all the starting materials was consumed as confirmed by TLC (<NUM>:<NUM>, EtOAc: Hexane). Reaction mixture was added in cold water (<NUM>). The reaction mixture was extracted with dichloromethane (<NUM> x <NUM>). Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mass was purified by column chromatography over silica gel using ethyl acetate (<NUM>- <NUM>%) in hexane as eluent to afford <NUM> as a white solid (Yield = <NUM> gm).

<NUM>H-NMR (<NUM>, DMSO): δ = <NUM> (d, <NUM>, J= <NUM>), <NUM> (d, <NUM>, J= <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>).

MTT assay is a simple and sensitive assay where, metabolic reducing activity of the cells is measured. The increase of this activity in time is taken as a parameter of cell growth. If treatment with a drug impairs this increase, the action may be a consequence of growth inhibition, cell killing or both. The compounds of Formula V to XIV, standard cytotoxic drug (e.g. Cisplatin) were tested at different concentrations (<NUM>,<NUM>,<NUM>,<NUM>) using breast and prostate cancer cell lines. All cell lines were cultured in a <NUM> incubator with a <NUM>% CO<NUM> environment. Compounds were dissolved in DMSO with a concentration of <NUM> (stock solution). Cells were seeded into <NUM>-well plates at suitable plating efficiency.

The MTT procedure followed was as follows. Briefly, the cells were plated in <NUM> well plate as per predetermined plating efficiency(Table1) The plates were then incubated for <NUM> hrs in <NUM>% CO<NUM> atmosphere at <NUM>. Appropriate concentrations of the drugs were then added to the plate and further incubation was carried out for <NUM> hrs (in <NUM>% CO<NUM> atmosphere at <NUM>. The assay plate was then centrifuged twice at <NUM> rpm for <NUM> mins and supernatant was then discarded. <NUM> ul of MTT solution (<NUM>/ml) was then added to each well of the plate and it was further incubated for 4hrs (in <NUM>% CO<NUM> atmosphere at <NUM>. ) Following <NUM> hr incubation, the plate was then centrifuged twice, and supernatant was aspirated off very carefully. <NUM> ul of DMSO was then added to each well to solublize. MTT crystals and mixed well by shaking the plate. XY graph of log Percent viability was then plotted against log drug concentration. IC50 (Drug concentration inhibiting the <NUM> % of cell population) was then calculated by regression analysis.

The Soft Agar Colony-formation Assay is an anchorage-independent growth assay in soft agar, which is one of the most stringent assays for detecting malignant transformation of cells. For this assay, malignant cells are cultured with appropriate controls in soft agar medium for <NUM>-<NUM> weeks. Following this incubation period, formed colonies can either be analyzed morphologically using cell stain and quantifying the number of colonies formed. The results of the assay are comparable to those obtained after injecting tumorigenic cells into nude mice and is regarded as the "gold standard" for testing the tumorigenicity of cells in vitro (one of the important features of cancer stem cells, CSCs).

Briefly, for Soft Agar Assay a mixture of <NUM> ul of 2X medium (taken appropriately as per cell line) and <NUM> ul of <NUM>% Bacto Agar were plated on to each well of <NUM> well micro titer assay plate. <NUM> ul of cells (Of specific plating efficiency pre-standardized for respective cell line) were mixed with <NUM> ul of 2X medium and <NUM> ul of <NUM> % of Bacto Agar and <NUM> ul of drug (of appropriate concentration) in a vial and transferred to the solidified pre-layers of the assay plates. The cells were then allowed to grow and form colonies at <NUM>. and <NUM>% CO<NUM> for <NUM> week. An intermittent feeding with <NUM> ul of appropriate 2X medium was performed after <NUM> days of experimental set up. 16ul of Alamar Blue (<NUM>/ml) was then added to all the wells to quantify the developed colonies. The plates were incubated for 24hrs at <NUM>. Absorbance was then measured at <NUM>. XY graph of log Percent viability was then plotted against log drug concentration. IC50 (Drug concentration inhibiting the <NUM> % of cell population) was then calculated by regression analysis.

In Vitro Sphere-forming Assay: Sphere assay measures the ability of Cancer Stem Cellss to form spheres in specially designed serum-free medium. We have used this assay to measure the killing efficiency of the test compounds as compared to the standard chemotherapeutic drug, Cisplatin.

Materials and Reagents:50X B27 Supplement (Life Technologies, Invitrogen, Catlog No.: <NUM>-<NUM>),Fibroblast Growth Factor (FGF) (Sigma-Aldrich, Catlog No.: F029125),Epidermal Growth Factor (EGF) (Sigma-Aldrich, Catlog No.: E9644), Insulin (Sigma, Catlog No.: <NUM>), Dulbecco's Modified Eagle Medium/F12 (HiMedia Catlog No.: AL139-<NUM>), Dulbecco's Phosphate Buffered Saline (HiMedia Catlog No.: TL1006),Trypan Blue (TC193),Prostate Epithelial Media (LONZA, Catlog No.: CC-<NUM>) MEGM (LONZA, Catlog No.: CC-<NUM>),Heparin (Sigma, Catlog No.: H3393),Penstrep (HiMedia, Catlog No.: A002).

Mammosphere Media Preparation (For <NUM>): <NUM> methyl cellulose autoclaved with magnetic stirrer Plain media (MEBM), <NUM> added and dissolved under magnetic stirring. After complete dissolution, add: FGF- <NUM>µL, EGF- <NUM>µL,Penstrep- <NUM>, Heparin- <NUM>µL.

Prostosphere Media Preparation (For <NUM>):<NUM> methyl cellulose autoclaved with magnetic stirrer, Plain media (Prostate Epithelial Basal Medium), <NUM> added and dissolved, under magnetic stirring. After complete dissolution, add: Insulin- <NUM>µL, B27- <NUM>, EGF- <NUM>µL, Penstrep- <NUM>.

Procedure: -The cells were trypsinised and made into single-cell suspension by passing through cell strainers (<NUM>µl and <NUM>µl, respectively), The cells were diluted at the concentration of <NUM> cells/<NUM>µL and suspended in either Mammosphere (for breast cell lines) or Prostosphere (for prostate cell lines). <NUM>µL of this suspension was added into each well of <NUM>-well suspension plates and incubated at <NUM>, <NUM>% CO<NUM> for <NUM> hrs. Appropriate concentrations of the drugs (<NUM>µL) were added into respective wells with <NUM>µL of stem cell culture medium. Plates were incubated at <NUM>, <NUM>% CO<NUM> for <NUM> hrs. After incubation <NUM>µL of the respective drug concentration and <NUM>µL of stem cell culture medium were added into each well and the plates were further incubated at <NUM>, <NUM>% CO<NUM> for <NUM> hrs. <NUM>µL of the respective drug concentration was added with <NUM>µL of stem cell culture medium again after incubation and plates were incubated again for <NUM> hrs at <NUM>, <NUM>% CO<NUM>. Number of primary spheres formed for each concentration was counted. A comparative graph of number of spheres formed was plotted against the concentration and the growth curve was compared with the positive control.

It is very important that the sensitivity of a cytotoxic drug towards malignant and normal cells is different. In the first place, the clinical use of drugs with a preferential toxicity towards malignant cells is preferred.

In order to test the activity of cytotoxic drugs towards normal cells, we performed MTT.

Assay for these cytotoxic drugs using lymphocytes obtained from a healthy donor.

Human lymphocytes can be readily isolated from peripheral blood. centrifuged at low speeds for 30mins. Briefly, diluted defibrinated fresh blood was overlaid gradually on HiSeP LSM1077 and centrifuged at low speed for 30mins. The lymphocyte layer (the buffy coat) (Fig)was carefully removed in a new collection tube. The buffy coat was given another wash, by the diluent buffer, to reduce the platelet contamination. The supernatant was discarded, and the pellet was resuspended in diluent buffer. The viability was checked by Haemocytometer. Cells with Viability and Purity of <NUM>% and more were considered for the assay. MTT assay was performed with these cells as described above with plating efficiency of <NUM>. 7million/ml.

Table <NUM> indicates that activity of Formula V on breast cancer cell line is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

The results indicate that activity of Formula V on prostate cancer cell line is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity exhibited by Formula V is on breast cancer cell line MDAMB231 is higher than standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula V is higher on prostate cancer cell line in soft Agar Assay.

Table <NUM> indicates Formula V is effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula V is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of Formula VI on breast cancer cell line is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM>. indicates that activity of FORMULA VI on Prostrate cancer cell line is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Results of MTT assay indicates that compound of Formula VI exhibits higher anticancer activity on breast and prostate Cancer cell lines compared to standard chemo therapeutic drug Cisplatin.

Table <NUM> indicates the anticancer activity of Formula VI is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula VI is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

The results Indicates that Formula VI exhibits higher anticancer activity on breast and prostate Cancer cell lines compared to standard chemotherapeutic drug Cisplatin in Soft Agar Assay.

Table <NUM> indicates that Formula VI is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula VI is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table15 indicates that activity of Formula VII on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula VII on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of FORMULA VII is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> results indicate the anticancer activity of Formula VII is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the that Formula VII is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula VII is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of FORMULA VIII on breast cancer cell lines is higher compared to standard therapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula VIII on prostate cancer cell lines is higher compared to standard therapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula VIII is higher on breast cancer cell line MDAMB231 compared to standard therapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula VIII is higher on prostate cancer cell line PC3 compared to standard therapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the that Formula VIII is more effective on spheres of MDAMB231 compared to standard therapeutic drug Cisplatin.

Table <NUM> indicates that Formula VIII is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of FORMULA IX on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula IX on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula IX is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula IX is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates that Formula IX is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula IX is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of Formula X on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula X on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula X is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula X is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates that Formula X is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of Formula XI on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of FORMULA XI on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula XI is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula XI is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates that activity of Formula XII on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula XII on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula XII is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula XII is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates that Formula XII is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula XII is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that activity of Formula XIII on breast cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates that activity of Formula XIII on prostate cancer cell lines is higher compared to standard chemotherapeutic drug Cisplatin in MTT assay.

Table <NUM> indicates the anticancer activity of Formula XIII is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates the anticancer activity of Formula XIII is higher on prostate cancer cell line PC3 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM> indicates that Formula XIII is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates that Formula XIII is more effective on spheres of PC3 compared to standard chemotherapeutic drug Cisplatin.

Table <NUM> indicates the anticancer activity of Formula XIV is higher on breast cancer cell line MDAMB231 compared to standard chemotherapeutic drug Cisplatin in soft Agar Assay.

Table <NUM>. indicates that Formula XIV is more effective on spheres of MDAMB231 compared to standard chemotherapeutic drug Cisplatin.

Claim 1:
A compound of Formula IV:
<CHM>
wherein R<NUM> and R<NUM> are each independently selected from -H, -OMe;
R is selected from:
<CHM>
wherein, R<NUM> is -OH;
R<NUM> is selected from -OMe, -OH;
R<NUM> is selected from -OMe, -OH;
R<NUM> is -H;
R<NUM> is -CH<NUM>;
R<NUM> and R<NUM> are each independently selected from -H, or R<NUM> and R<NUM> together form lactone, or -C(O)OC<NUM>H<NUM>;
and wherein the compound is selected from:
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>