Abstract: The present invention provides a method for synthesizing etelcalcetide or salts thereof, comprising the steps of: (a) synthesizing the D-amino acids in the formula (I) sequentially by Fmoc solid-phase synthesis, using a solid support as a starting material in solid phase peptide synthesis and sequentially synthesizing a D-form amino acid of formula (I) by Fmoc chemistry; deprotecting Fmoc group and acetylating the amino group to obtain a sequence A comprising protecting groups (PG) in the side chain of D-Cys and D-Arg; (b) removing the protecting group in the side-chain of D-Cys of the sequence A to form a sequence B; (c) disulfide formation at D-Cys of the sequence B by (PG)-L-Cys-OH to obtain a sequence C; (d) using a cleavage solution to remove the protecting groups of the sequence C to give etelcalcetide as formula (I). The present invention can shorten the steps and time for preparing Etelcalcetide.

Abstract: The present invention provides a method for synthesizing etelcalcetide or salts thereof, comprising the steps of: (a) synthesizing the D-amino acids in the formula (I) sequentially by Fmoc solid-phase synthesis, using a solid support as a starting material in solid phase peptide synthesis and sequentially synthesizing a D-form amino acid of formula (I) by Fmoc chemistry; deprotecting Fmoc group and acetylating the amino group to obtain a sequence A comprising protecting groups (PG) in the side chain of D-Cys and D-Arg; (b) removing the protecting group in the side-chain of D-Cys of the sequence A to form a sequence B; (c) disulfide formation at D-Cys of the sequence B by (PG)-L-Cys-OH to obtain a sequence C; (d) using a cleavage solution to remove the protecting groups of the sequence C to give etelcalcetide as formula (I). The present invention can shorten the steps and time for preparing Etelcalcetide.

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 caspofungin acetate comprising the steps of: A. selectively dehydrating pneumocandin Bo to obtain a nitrile; B. reducing the nitrile to primary amine; C. reacting the primary amine with an arylthiol in a suitable solvent to obtain a thioether; and D.

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: A process for making mycophenolate mofetil comprising: conducting a catalytic transesterification by reacting a low-carbon alkyl ester of mycophenolic acid with 2-morpholinoethanol [also named as 4-(2-hydroxyethyl) morpholine] to obtain a crude product of mycophenolate mofetil, which is then isolated and purified.

Abstract: A process for making mycophenolate mofetil comprising: conducting a catalytic transesterification by reacting a low-carbon alkyl ester of mycophenolic acid with 2-morpholinoethanol [also named as 4-(2-hydroxyethyl) morpholine] to obtain a crude product of mycophenolate mofetil, which is then isolated and purified.