Glycolactam compounds, process for preparation and uses thereof

A process for the synthesis of a piperidine alkaloids or an analogues thereof from a compound of formula 1, comprising:

• a) adding a solution of ruthenium (III) chloride hydrate and sodium periodate in distilled water to a solution of a glycolactam compound of formula IB in acetonitrile at a temperature ranging from 0° C. to 5° C. to form a reaction mixture;
• b) stirring the reaction mixture for a time period ranging from 30 to 40 minutes at a temperature ranging from 0° C. to 5° C. to form a dihydroxylated compound of a glycolactam compound of formula IB;
• c) adding Pd/C to said solution of said dihydroxylated glycolactain compound of formula IB in methanol/ethanol/ethyl acetate followed by stirring for a time period ranging from 14 to 16 hours at a temperature of from 30 to 35° C. under a hydrogen atmosphere to form a Mannolactam;
• d) alternatively, adding borane dimethyl sulphide to a solution of a dihydroxylated compound of a glycolactam compound of formula IB a solvent at a temperature ranging from. 0° C. to 5° C. for 1 to 2 hours followed by stirring at a temperature ranging from 30 to 35° C. for 4 to 6 hours followed by stirring at a refluxt temperature for a time period ranging from 2 to 4 hours, to obtain piperidine derivative of formula IB;
• e) adding Pd/C to a solution of said piperidine derivative of formula IB in methanol/ethanol/ethyl acetate followed by stirring for a time period ranging from 14 to 16 hours at a temperature ranging from 30 to 35° C. under hydrogen atmosphere to form a benzyl protected deoxymannojirimycin;
• f) hydrogenating of said benzyl protected product deoxymannojirimycin by a hydrogenating agent in a solvent to form a deoxynojirimycin;
• g) alternatively, adding nickel(II) chloride hexahydrate to a cooled solution of the glycolactam compound of formula IB in alcohol followed by stirring for 10 to 15 minutes at a temperature ranging from 0° C. to 5° C. to obtain a solution;
• h) adding sodium borohydride to said solution of step g at a temperature ranging from 0° C. to 5° C. for a time period ranging from 10 to 15 minutes;
• followed by stirring for 2 to 2.5 hours at a temperature ranging from 25 to 30° C. to form saturated glycolactum product;
• i) adding Lawesson's reagent to a solution of the saturated glycolactum product of step h in THF or dioxane followed by stirring said solution for a time period ranging from 4 to 12 hours to form thiolactum;
• j) stirring the solution of said thiolactam of step i and 1-bromoethyl acetate in diethylether or dichloromethane for a time period ranging from 24 to 36 hours, removing said solvent to form a thionium salt, adding triphenylphosphine to a solution of said thionium salt in acetonitrile followed by stirring for a time period ranging from 10 to 15 minutes by further adding triethyl amine to the reaction mixture followed by heating at a temperature ranging from 70 to 75° C., for a time period ranging from 26 to 27 hours and filtering the product to form an enamide;
• k) stirring the enamide of step j in a mixture of sodium carbonate and 10% palladium on carbon in ethanol or methanol under an atmosphere of hydrogen for a time period ranging from 16 to 48 hours to form a piperidine ester;
• l) alternatively, adding sodium cyanoborohydride to a solution of the enaminoester and bromocresol green in methanol, adding 5% methanolic HCl solution drop wise until a yellow color persists in solution, stirring said solution for a time ranging from 2 to 3 hours, periodically adding HCl to maintain a yellow color, diluting the mixture with CH2Cl2, washing with 10% aqueous NaHCO3 to form a piperidine ester;
• m) adding lithium aluminum hydride to a solution of the piperidine ester of step k or piperidine ester of step l in diethylether or tertrahydrofuran followed by stirring for a time ranging from 2 to 4 hours, quenching the reaction by adding water and 15% aqueous NaOH, stirring the mixture for a time ranging from 1 to 2 hours to form a piperidine alcohol;
• n) adding a solution of dimethyl sulfoxide in dieholoromethane a solution of oxalyl chloride in dicholoromethane at a temperature ranging from −70° C. to −80° C. for a time period ranging from 10 to 11 hours, adding a solution of piperidine alcohol of step m in dichoromethane to said reaction mixture, followed by stirring for 45 to 50 minutes at a temperature ranging from −65° C. to −70° C. adding trimethylamine to said solution followed by stirring for a time period ranging from 20 to 30 minutes at a temperature ranging from −65° C. to −70° C. and then warming said solution to room temperature for the time period ranging from I to 2 hours to form a piperidine aldehyde;
• o) refluxing a mixture of 2-(7-bromoheptyl)-2-ethyl-1,3-dioxolane and triphenylphosphine in toluene for a time period ranging from 40 to 50 hours, cooling the solution to room temperature, removing the solvent, adding tetrahydrofuran to said mixture and adding a solution of butyl lithium in hexane to the phoshonium salt at a temperature ranging from −78° C. to −80° C. followed by stirring for 10 to 20 minutes at −78° C. and then continuing the stirring for a time ranging from 1 to 3 hours at a temperature ranging from 25° C. to 30° C., cooling the resulting yield solution to 78° C. and adding the piperidine aldehyde of step q in tetrahydrofuran, followed by warming the mixture −45° C. over 2 to 4 hours, continuing the stirring for an additional 1 to 2 hours at −45° C., warming to 0° C. for 3 to 5 hours, and stirring an additional 2 to 4 hours at the temperature ranging from 25° C. to 30° C. to form a condensed product;
• p) adding hydrochloric acid to said solution of the above condensed product of step o in tetrahydrofuran, followed by stirring for 2 to 4 hours, adding saturated aqueous sodium bicarbonate and extracting the mixture dichloromethane, drying and concentrating the organic layers to afford residue, dissolving the residue in ethanol or methanol and adding cone. HCl, adding 10% Pd on carbon followed by stirring under H2 at 3 atm pressure for 20 to 30 hours to form (+)-Prosophylline or (+)-Prosopinine compounds.