Abstract: The present invention relates to a method for purifying polyunsaturated fatty acid using a continuous reactor, and the method comprises: (a) complexing step, (b) cleaning step, (c) extracting step, and (d) concentrating and drying step. The method of the present invention reacts a polyunsaturated fatty acid and a silver salt aqueous solution in a continuous reactor to form a complex of the polyunsaturated fatty acid and silver, and then cleans the complex with a first organic solvent to improve the purity of the complex; afterwards, a second organic solvent is used to extract the purified polyunsaturated fatty acid. The method of the present invention can continuously produce polyunsaturated fatty acids with high yield and high purity.

Abstract: A method for preparing 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) is provided, which has advantages of high conversion rate and no 31,42-bis(dimethyl phosphinate) Rapamycin (III) generated. In the method of the present invention, Rapamycin (II) is firstly reacted with triethyl chlorosilane in a base condition to form 31,42-bis(triethylsilylether) Rapamycin (IV-b), followed by a selective deprotection process to obtain 31-triethylsilylether Rapamycin (V-b). Next, a phosphorylation reaction is performed by using dimethylphosphinic chloride under a base solution to obtain a crude product. Finally, a deprotection reaction is performed in a diluted sulfuric acid solution to obtain a crude product of Ridaforolimus (I). Since the conversion rate of each step of the method of the present invention is higher than 98%, it indicates that the method of the present invention is suitable for industrial production.

Abstract: A method for preparing 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) is provided, which has advantages of high conversion rate and no 31,42-bis(dimethyl phosphinate) Rapamycin (III) generated. In the method of the present invention, Rapamycin (II) is firstly reacted with triethyl chlorosilane in a base condition to form 31,42-bis(triethylsilylether) Rapamycin (IV-b), followed by a selective deprotection process to obtain 31-triethylsilylether Rapamycin (V-b). Next, a phosphorylation reaction is performed by using dimethylphosphinic chloride under a base solution to obtain a crude product. Finally, a deprotection reaction is performed in a diluted sulfuric acid solution to obtain a crude product of Ridaforolimus (I). Since the conversion rate of each step of the method of the present invention is higher than 98%, it indicates that the method of the present invention is suitable for industrial production.

Abstract: The present invention provides two synthetic routes for the preparation of Temsirolimus (compound 1b and analog of Temsirolimus 1a). The first route includes the synthesis of CCI-779 by directly reacting rapamycin (4b) or Prolyl-rapamycin (4a) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base, followed by deprotection to give CCI-779 or Proline CCI-779. The second route includes a process involving a reaction of rapamycin-OH-31-sily ether (4d) or Prolyl-rapamycin-OH-31-sily ether (4c) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base and followed by subsequent hydrolysis step to obtain the desired CCI-779 or Proline CCI-779. Compound 11, as described in this invention, is stable at room temperature, cost effective and ease of processing.

Abstract: A process for making Biolimus A9 comprises reacting sirolimus (or rapamycin) with alkyl benzene sulfonate under the catalyzing of organic base and in the presence of organic solvent to undergo a nucleophilic substitution reaction to obtain the Biolimus A9 with high yield, not only for small-scale laboratory experiment, but also for rendering reproducibility of high yield even after process amplification.

Abstract: The present invention provides two synthetic routes for the preparation of Temsirolimus (compound 1b and analog of Temsirolimus 1a). The first route includes the synthesis of CCI-779 by directly reacting rapamycin (4b) or Prolyl-rapamycin (4a) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base, followed by deprotection to give CCI-779 or Proline CCI-779. The second route includes a process involving a reaction of rapamycin-OH-31-sily ether (4d) or Prolyl-rapamycin-OH-31-sily ether (4c) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base and followed by subsequent hydrolysis step to obtain the desired CCI-779 or Proline CCI-779. Compound 11, as described in this invention, is stable at room temperature, cost effective and ease of processing.

Abstract: A process for making Biolimus A9 comprises reacting sirolimus (or rapamycin) with alkyl benzene sulfonate under the catalyzing of organic base and in the presence of organic solvent to undergo a nucleophilic substitution reaction to obtain the Biolimus A9 with high yield, not only for small-scale laboratory experiment, but also for rendering reproducibility of high yield even after process amplification.