M/s. Hemmo Pharmaceuticals Pvt. Ltd.
1. Manufacturing process of Leuprorelin
Boc- Pro- Merrifield Resin
Coupling of Boc-Arg(HCL)-OH
Boc-Arg-Pro-M. Resin Resin
Coupling of Fmoc-Leu-OH
Fmoc-Leu-Arg-Pro-M.Resin
Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-D-Leu-Arg-Pro-M.Resin Resin
Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Tyr(tBu)-D-Leu-Arg-Pro-M.Resin
Coupling of Fmoc-Trp-OH
Fmoc-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg-Pro-M. Resin
Coupling of Fmoc-His(trt)-OH
Fmoc-Trp-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg-Pro-M.Resin
Coupling of p-Glu-OH Fmoc-His(trt)-Trp-Ser(tBu)-Tyr(tRu)-D-Leu-Leu-Arg-Pro-M.Resin
Clevage p-Glu-His(trt)-Trp-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg-Pro-NH2
Deprotection
p-Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NH2
Purification Concentration and Freeze Drying
LEUPRORELIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
2. Manufacturing process of Desmopressin
Boc- Gly-Merrifield Resin
Coupling of Boc-D-Arg(HCL)-OH
Boc-D-Arg-Gly-M.Resin
Coupling of Fmoc-Pro-OH
Fmoc-Pro-D-Arg-Gly-M.Resin
Coupling of Fmoc-Cys(trt)-OH
Fmoc-Cys(trt)-Pro-D-Arg-Gly-M.Resin
Coupling of Fmoc-Asn-OH
Fmoc-Asn-Cys(trt)-Pro-D-Arg-Gly-M.Resin
Coupling of Fmoc-Phc-OH
Fmoc-PHe-Gln-Asn-Cys(trt)-Pro-D-Arg-Gly-M.Resin
Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-Phe-Gln-Asn-Cys(trt)-Pro-D-Arg-Gly-M.Resin
Clevage
Mpa(trt)-Tyr(tBu)-Phe-Gln-Asn-Cys(trt)-Pro-D-Arg-Gly-NH2
Deprotection
Mpa-Tyr-Phe-Gln-Asn-Cys-pro-D-Arg-Gly-NH2
Oxidation Purification Concentration And freeze drying
DESMOPRESSIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
3. Manufacturing process of Somatostatin
Cl-Trityl Resin
Coupling of Fmoc-Cys(trt)-OH
Fmoc-Cys(trt)-Resin
Coupling of Fmoc-Scr(tBu)-OH
Fmoc-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Thr(tBu)-OH
Fmoc-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Phe-OH
Fmoc-Tyr(tBu)-D-Leu-Arg-Pro-M.Resin
Coupling of Fmoc-Thr(tBu)-OH
Fmoc-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Lys(Boc)-OH
Fmoc-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Lys(Boc)-OH
Fmoc-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Trp-OH
Fmoc-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Phe-OH
Fmoc-Phe-Trp-Lys(Boc)-thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Phe-OH Fmoc-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe0Thr(tBu) -Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Asn-OH
LEUPRORELIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Fmoc-Asn-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr-tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Lys(Boc)-OH
Fmoc-Lys(Boc)-Asn-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Cys(trt)-OH
Fmoc-Cys(trt)-Lys(Boc)-Asn-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-cys(trt)-Resin
Coupling of Fmoc-Gly-OH
Fmoc-Gly-Cys(trt)Lys(Boc)-Asn-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Ala-OH
Fmoc-Gly-Cys(trt)-Lys(Boc)-Asn-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Ala-OH
H-Ala-Gly-Cys(trt)-Lys(Boc)-Asn-Phe-Phe-Trp-Lys(Boc)-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Cys(trt)-Resin
Coupling of Fmoc-Phe-OH
H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe -Thr-Scr-Cys-OH
Oxidation Purification Concentration And Freeze Drying SOMATOSTATIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
4. Manufacturing Process of GonaDorelin Acetate
Boc-Pro-O-Merrifield Resin
Deprotection of Fmoc Coupling of Boc-Pro-OH
Boc-Pro-Gly -O-Resin
Deprotection of Fmoc Coulping of Fmoc-Arg(Pbf)- OH Fmoc-Arg-(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of FMoc-Tyr(tBu)-OH Fmoc-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of Fmoc-Gly-OH Fmoc-Gly-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Tyr(tBu)-Gly-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Ser(tBu)-Tyr(tBu)-Gly-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of FMoc-Trp-OH
Fmoc-Trp-Ser(tBu)-Tyr(tBu)-Gly-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of Fmoc-His(Trp)-OH
Fmoc-His(Trt)-Trp-Ser(tBu)-Gly-Leu-Arg(Pbf)Pro-Gly-O-Resin
Deprotection of Fmoc Coupling of p-Glu-OH
p-Glu-His(trt)-Trp-Ser(tBu)-Tyr(tBu)-Gly-Leu-Arg(Pbf)-Pro-Gly-O-Resin
Cleavage from Resin
p-Glu-His(Trt)-Trp-Ser(tBu)-Tyr(tBu)-Gly-Leu-Srg(Pbf)-Pro-Gly-NH2
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Deprotecation of side chains
Crude Gonadorelin
Preperative HPLC Purification
Purified Gonadorelin Phosphate
Desalting and purification by preparative HPLC
Gonadorelin Acetate
Concentration by Diaion and freeze drying
GONADORELIN ACETATE POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
5. Manufacturing process of Salmon calcitonin
Rink Amide MBHA Resin
Coupling of Fmoc-ProOH
This is repetead for 31 times(each time with the amino acid derivative
correspondence to the position in the chain) and at the end of step 31 the peptide resin is complete and has the following sequence:
Fmoc-Cys(Trt)-Ser(tBu)-Asn-Leu-Ser(tBu)-Thr(tBu)-Cys(Trt)-Val-Leu-Gly-Lys(Boc)-Leu- Ser(Yma, Mepro)-Glen-Glu(tBu)-Leu-His(Trt) -Lys(Boc)-Leu-Gln-Thr(tBu)-Tyr(tBu)-Pro- Arg(Pbf)Thr(tBu)-Asn-Thr(tBu)-Gly-Ser(tBu)-Gly-Thr(tBu)-Po-MBHA resin
XXXII. Clevage of peptide from resin and side chain Deprotection H-Cys(Trt)-Ser(tBu)-Asn-Leu-Ser(tBu)-Thr(tBu) -Cys(Trt)-Val-Leu-Gly-Lys(Boc)-Leu- Ser(Yme,Mepro),Gln-Glu(tBu)-Leu-=His(Trt) -Lys(Boc)-Leu-Gln-Thr(tBu)-Tyr(tBu)- Pro-Arg(Pbf)Thr(tbu)-Gly-Ser(tBu)-Gly-Thr(tBu0-Pro-NH2
XXXII. Oxidation
Oxidised Salmon Calcitonin
XXXIV Concentration by preparative HPLC
Crude Salmon Calcitonin
XXXV Purification of crude by preparative HPLC
Purified Salmon Calcitonin
XXXVI Desalting & Concentration by Preparative HPLC
Desalted Salmon Calcitonin
XXXV Dowex ion Exchange Chromatography
SALMON CALCITONIN
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
6. Manufacturing Process Terlipressin
Rink amide Resin
Deprotection of Fmoc Coupling of Fmoc-G(ly)-Oh
Fmoc-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Lys(Boc)-OH
Fmoc-Lys(Boc)-Gly0Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Pro-OH
Fmoc-Pro-(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Cys(Tri)-OH
Fmoc-Cys(Trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Asn-OH
Fmoc-Gln-Asn-Cys(trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Gln-OH
Fmoc-Gln-Asn-Cys(trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Phe-OH
Fmoc-Phe-Gln-Asn-Cys(trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-Phe-Gln-Asn-Cys(Trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-Cys(Trt)-OH Fmoc-Gln-Asn-Cys(trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Fmoc-Cys(Trt)-Tyr(tBu)-Ohe-Gln-Asn-Cys(Trt)-Pro-Lys(Boc)Coupling of Fmoc-Gly-Gln-OH -Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-(Gly)-OH
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Fmoc-Gly-Cys(Trt)-Tyr(tBu)-Phe-Gln-Asn-Cys(Trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-(Gly)-OH
Fmoc-Gly-Gly-Cys(trt)-Tyr(tBu)-Phe-Gln-Asn-Cys(Trt)-Pro-Lys(Boc)-Gly-Rink Amide Resin
Deprotection of Fmoc Coupling of Fmoc-(Gly)-OH
Boc-Gly-Gly-Gly-Cys(Trt)-Tyr(tBu)-Phe-Gln-Asn-Cys(Trt)-Pro-Lys(Boc)Gly-Rink Amide Resin
Clevage of peptide from resin and side chains deprotection
H-Gly-Gly-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2
Oxidation of Terlipressin Bis-SH
Concentration of pre-filterate oxidized Terlipressin by dizion
Purification of crude terlipressin by Preparative HPLC purification
Dowex Ion Exchange of Terlipressin
TERLIPRESSIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
7. Manufacturing process of Octreotide
H-Thr(tBu)Ol-2ClTrt-Resin
1. Coupling of Fmoc –Thr(tBu)-OH
H-Cys(trt)-Thr(tBu)Ol-2ClTrt-Resin
II. Coupling of Fmoc –Thr(tBu)-OH
H-Thr(tBu)-Cys(trt)-Cys(trt)-Thr(tBu)Ol-2CITrt-Resin
III. Coupling of Fmoc-Lys(tBu)-OH
H-Lys(Boc)-Thr(tBu)-Cys(trt)-Thr(tBu)Ol-2CITrt-Resin
IV. Coupling of Fmoc-D-Trp-OH
H-D-Trp-Lys(Boc)-Thr(tBu)-Cys(trt)-Thr(tBu)Ol-2ClTrt-Resin
V. Coupling of Fmoc-Phe-OH
H-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(trt)-Thr(tBu)Ol-2ClTrt-Resin
VI. Coupling of Fmoc-Cys(Trt)-OH
H-Cys(trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(trt)-Thr(tBu)Ol-2ClTrt-Resin
VII. Coupling of Boc-D-Phe-OH
Boc-D-Phe-Cys(trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(trt)-Thr(tBu)Ol-2ClTrt-Resin
1) VIII. Deprotection of side chains and
Octreotide Bis-SH Trifluoroacetate
IX. Oxidation
Oxidised Octreotide Trifluoroacetate
X. Concentration by Diaion and
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Crude Octreotide Trifluoroacetate
X. Concentration of Diaion and
Puriified Octreotide Trifluoroacetate
XII. Qowex Ion Exchange
OCTREOTIDE ACETATE
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
8. Manufacturing process of Buserelin
Boc-Pro-O-Resin
I.Coupling of Boc-Srg(HCL)-OH
Boc-Arg(HCL)-Pro-O-Resin
II.Coupling of Fmoc-Leu-OH
Fmoc-Leu-(HCL)-Pro-O-Resin
III. Coupling of Fmoc-Lys(tBu)-OH
Fmoc-D-Ser(tBu)-Leu-Arg(HCL)-Pro-O-Resin
IV. Coupling of Fmoc-Tyr(Clt)-OH
Fmoc-Tyr(Clt)-D-Ser(tBu)-Leu-Arg(HCL)-Pro-O-Resin
V. Coupling of Fmoc-Ser(Trt)-OH
Fmoc-Ser(Trt)-Tyr(Clt)-D-Ser(tBu)-Leu-Arg(HCL)-Pro-O-Resin
VI. Coupling of Fmoc-Trp-OH
Fmoc-Trp-Ser(Trt)-Tyr(Clt)-D-Ser(tBt)-Leu-Arg(HCL)-Pro-O-Resin
VII. Coupling of Fmoc-His(Mmt)-OH
Fmoc-His(Mmt)-Trp-Ser(Trt)-Tyr(Clt)-D-Ser(trt)-Leu-Arg(HCL)-Pro-O-Resin
VIII.Coupling of p-Glu-OH
P-Glu-His(Mmt)-Trp-Ser(Trt)-Tyr(Clt)-D-Ser(trt)-Leu-Arg(HCL)-Pro-O-Resin
IX.Cleavage by ethyl Amine
P-Glu-His(Mmt)-Trp-Ser(Trt)-Tyr(Clt)-D-Ser(tBu)-Leu-Arg(HCL)-Pro-NHEt
X. Deprotection of Side Chain
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Buserelin Phosphate
XI.Desaltation and purification to obtain Buserlin Acetate Buserelin Acetate
XIII.Dowex Ion Exchange
BUSERELIN EP POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
9. Manufacturing process of Decapeptide
Rink Acetate Resin
I.Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-® [=®denotes the resin]
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Trp-OH Fmoc-Trp-Tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Ser(tBu)-Trp-Tyr(tBu)- ®
1.Deprotection of Fmoc 2.-Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Ser(tBu)-Ser-Trp-Tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-Ser(tBu)-Trp-Tyr(tBu)- ®
1.-Deprptection of Fmoc 2.-0Coupling of Fmoc-Lys(Boc)-OH
Fmoc-Lys(Boc)-Tyr(tBu)-Ser(tBu)-Ser(tBu) -Trp-Tyr(tBu)
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Arg(Pbf)-OH
Fmoc-Arg(Pbf)-Lys(Boc)-Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp-Tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Ser(tBu)-Arg(Pbf)-Lys(Boc)-Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp-Tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Couipling of Arg(Pbf)-OH
Fmoc(Pbf)-Ser(tBu)-Arg(Pbf)-Lys(Boc)-Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp-tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Tyr(tBu)- ® M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Fmoc-Arg(Pbf)-Ser(tBu)-Arg(Pbf)-Lys(Boc)-Tyr(tBu)-Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp-Tyr(tBu)- ®
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-Arg(Pbf)-Ser(tBu)-Arg(Pbf)-Lys(Boc)-Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp-Tyr(tBu)- ®
1.-Deprptection of Fmoc 2.-0Coupling of Parahydroxyphenyl Propionic acid PHPP-Tyr(tBu)-Arg(Pbf)-Ser(tBu)-Arg(Pbf)-Lys(Boc) -Tyr(tBu)-Ser(tBu)-Ser(tBu)-Trp
t- Cleavage and side chain Deprotection with TFA
PHPP-Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr-NH2
Crude Decapeptide 1.-Purification by preparative HPLC 2.-Final freeze drying PHPP-Tyr-Arg -Ser-Arg -Lys-Tyr -Ser-Ser -Trp-Tyr-NH2
DECAPEPTIDE TRIFLUOROACETATE
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
10. Manufacturing process of Cetrorelix
Boc-D-Ala-O-Merrifield Resin
I.Coupling of Boc-Pro-OH
Boc-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Boc 2.-Coupling of Fmoc-Arg(HCL)-OH
Boc-Arg-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Boc 2.-coupling of Fmoc-Leu-OH
Fmoc-Leu-Arg-Pro-D-Ala-O-Merrifield Resin
1.Deprotection of Fmoc 2.-Coupling of Fmoc-D-Cit-OH
Fmoc-D-Cit-Leu-Arg-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Tyr(tBu)-D-Cit-Leu-Arg-Pro-D-Ala-O-Merrifield Resin
1.-Deprptection of Fmoc 2.-0Coupling of Fmoc-Ser(tBu)-OH
Fmoc-Ser(tBu)-Tyr(tBu)-D-Cit-Leu-D- Ala-O-Merrifield Resin
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-D-Pal(3)-OH
Fmoc-D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-Cit-Leu-Arg-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Fmoc 2.-Coupling of Fmoc-D-Phe(4-Cl)-OH
Fmoc-D-Phe(4-Cl)-D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-Cit-Leu-Arg-Pro-D-Ala-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Fmoc 2.-Couipling of Arg(Pbf)-OH
Fmoc-D-Phe(4-Cl)-D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-Cit-Leu-Arg-Pro-D-Ala-O-Merrifield Resin
1.-Deprotection of Fmoc 2.-Coupling of Ac-D-Ala(2-Naphthyl)-Oh
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
AC-D-Ala(2-Naphthyl)-D-Phe(4-Cl)-D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-Cit-Leu-Arg-Pro-D-Ala-O-Merrifiele Resin
1.-cleavage with ammonia
AC-D-Ala(2-Naphthyl-D-Phe(4-Cl)-D-Phe(4-Cl)D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-CitLeu-Arg-Pro-D-Ala-O-Merrifield Resin
1.Side chain deprotection
AC-D-Ala(2-Naphthyl)-D-Phe(4-Cl)-D-Pal(3)-Ser(tBu)-Tyr(tBu)-D-Leu-Arg(HCL)-Pro-D-Ala-NH2
Crude Decapeptide 1.-Purification by preparative HPLC 2.-Purification,Desalting by Preparative HPLC 3.-Concentration by preparative HPLC Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-tyr-D4.-Cit-Final-Leu filteration-Arg-Pro and -freezeD-Ala -NH2 drying
CETRORELIX ACETATE
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
11. Manufacturing process of Carbetocin
Boc-Gly-O-Merrifield Resin
Deprotection of Boc Coupling of Boc-Pro-Leu-OH
Boc-Pro-Gly-O-Merrifield Resin
1.-Deprotection of Boc 2.-Coupling of Fmoc-Cys(Bzl)-OH
Fmoc-Cys(Bzl)-Pro-Leu-Gly-O-Merrifield Resin
Deprotection of Boc Coupling of Fmoc-Asn-OH
Fmoc-Cys(Bzl)-Pro-Leu-Gly-O-Merrifield Resin
Deprotection of Fmoc Coupling of Fmoc-Gln-OH
Fmoc-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-O-Merrifield Resin
Deprotection of Fmoc Coupling of Fmoc-Gln-OH
Fmoc-1le-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-O-Merrifield Resin
Deprptection of Fmoc Coupling of Fmoc-Tyr(OMe)-OH
Fmoc-Tyr(OMe)-1le-Gln-Asn-Cys(Bzl)-Pro- Leu-Gly-O-Merrifield Resin
Deprotection of Fmoc Coupling of 4-Chloro-Butyric Acid
Cl-CH2-CH2-CH2-CO-Tyr(OMe)-1le-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-O-Merrifield Resin
Cleavage from resin & Reduction of protection groups
Cl-CH2-CH2-CH2-C)-Tyr(OMe)-1le-Gln-Asn-Cys-Pro-Leu-Gly-NH2
Oxidation (Cyclisation)
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Concentration and freeze drying of crude
Preparative HPLC Purification
PURE CARBETOCIN POWDER
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
12. Manufacturing process of Bivalirudin
2-Chloro Triyl Resin
Coupling of Fmoc-Leu-OH Deprotection of Fmoc
H-Leu-Cl-Trt-Resin
Coupling of Fmoc-Tyr(tBu)-OH Deprotection of Fmoc
H-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Glu(tBu)-OH Deprotection of Fmoc
H-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Glu(tBu)-OH Deprotection of Fmoc
H-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-1le-OH Deprotection of Fmoc
H-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-1le-OH Deprotection of Fmoc
H-1le-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu) -Leu-Cl-Trt-Resin
Coupling of Fmoc-Glu(tBu)-OH Deprotection of Fmoc
H-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Glu(tBu)-OH Deprotection of Fmoc
H-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Phe-OH Deprotection of Fmoc
H-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Asp(tBu)-OH Deprotection of Fmoc M/s. Hemmo Pharmaceuticals Pvt. Ltd.
H-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Gly-OH Deprotection of Fmoc
H-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Tyr9tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Asn-OH Deprotection of Fmoc
H-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Gly-OH Deprotection of Fmoc
H-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Gly-OH Deprotection of Fmoc
H-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Gly-OH Deprotection of Fmoc
H-Gly-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Pro-OH Deprotection of Fmoc
h-Pro-Gly-Gly-gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu) -Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Arg(Pbf)-OH Deprotection of Fmoc
H-Arg(Pbf)-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-Tyr(tBu)-Leu-Trt- Resin
Coupling of Fmoc-Pro-OH Deprotection of FMoc
H-Pro-Arg(Pbf)-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)-Glu(tBu)-
Tyr(tBu)-Leu-Cl-Trt-Resin
Coupling of Fmoc-Pro-OH Deprotection of Fmoc
Boc -D-Phe-Pro-Arg(Pbf)-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro=Glu(tBu)-Glu(tBu)- Tyr(tBu)-Leu-Cl-Trt-Resin
Cleavage of Peptide resin
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Boc-D-Phe-Pro-Arg(Pbf)-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp(tBu)-Phe-Glu(tBu)-Glu(tBu)-Ile-Pro-Glu(tBu)- Glu(tBu)-Tyr(tBu)-Leu-OH
Deprotection of side chains
H-D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Asp-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH
Purification of preparative HPLC Final Filtration
BIVALIRUDIN TRIFLUOROACETATE
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
13. Manufacturing process of Goserelin
Boc-Pro-Merrifield Resin
1.-Deprotection of Boc 2.-Coupling of Moc-Arg-OH.HCL
Boc-Arg-Pro-Merrifield Resin
1.Deprotection of Boc 2.Coupling of Fmoc-Leu-OH
Fmoc-Leu-Arg-Pro-Merrifield Resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-D-Ser(tBu)-OH
Fmoc-D-Ser(tBu)-Leu-Arg-Pro-Merrifield resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-Tyr(Cltrt)-OH
Fmoc-Tyr(cltrt)-D-Ser(tBu)-D-Ser(tBu)-Leu-Arg-Pro-Merrifield resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-Ser(trt)-OH
Fmoc-Ser(trt)-Tyr(Cltrt)-D-Ser(tBu)-Leu-Arg-Pro-Merrifield Resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-Trp-OH
Fmoc-Trp-Ser(trt)-Tyr(Cltrt)-D-Ser(tBu)-Leu -Arg-Pro-Merrifield resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-His(Mmt)-OH
Fmoc-His(Mmt)-Trp-Ser(trt)-tyr(Cltrt)-D-Ser(tBu)-Leu-Arg-Pro-Merrifield Resin
1.Deprotection of Fmoc 2.Coupling of Fmoc-PlyGle-OH
PyGlu-His(Mmt)-Trp-Ser(trt)-Tyr(Cltrt)D-Ser(tBu)-D-Ser(tBu)-Leu-Arg-Pro-Merrifield resin
Hydrazine Hydrate cleavage of Peptide Resin
PyGlu-His(Mmt)-Trp-Ser(trt)-Tyr(Cltrt)-D-Ser(tBu)-Leu-Arg-Pro-NH-NH2
Coupling of Prot Goserelin Hydrazide with Semicurbazide Hydrochloride
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
PyGlu-His(Mmt)-Trp-Ser(trt)-Tyr(Cltrt)-D-Ser(tBu)-Leu-Arg-Pro-NH-NH-CO-NH2
2% TFA/DCM Cleavage
PyGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NH-NH-CO-NH2
1.Purification 2.Desalting
Pyglu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NH-NH-CO-NH2
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
14. Manufacturing process of Triptorelin
Rink Amide AM Resin
1.Coupling of Fmoc-Gly-OH
Fmoc-Pro-Gly-Rink Amide AM Resin
2.Coupling of Fmoc-Pro-OH
Fmoc-Pro-Gly-Rink Amide AM Resin
3.Coupling of Fmoc-Arg(Pbf)-OH
Fmoc-Arg(Pbf)-Pro-Gly-Rink Amide AM Resin
4.Coupling of Fmoc-Leu-OH
Fmoc-Leu-Arg(Pbf)-Pro-Gly-Rink Amide AM Resin
5.Coupling of Fmoc-D-Trp-OH
Fmoc-D-Trp-Leu-Arg(Pbf)-Pro-Gly-Rink Amide AM resin
6.Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Tyr(tBu)-D-Leu-Arg(Pbf)-Pro-Gly-Rink amide AM resin
7.Coupling of Fmoc-Tyr(tBu)-OH
Fmoc-Ser(tBu)-Tyr(tBu)-D-Trp-Leu-Arg(Pbf)-Pro-Gly-Rink Amide AM resin
8.Coupling of Fmoc-Trp-OH
Fmoc-Trp-Ser(tBu)-Tyr(tBu)-D-Trp-Leu-Arg(Pbf)-Pro-Gly-Rink amide AM Resin 9.coupling of Fmoc-His(Trt)-OH
Fmoc-His(Trt)-Trp-Ser(tBu)-Tyr(tBu)-D-Trp-Leu-Arg(Pbf)-Pro-Gly-Rink amide AM resin
10.Coupling of p-Glu-OH
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
p-Glu-His(Trt)-Trp-Ser(tBu)-Tyr(tBu)-D-Trp-Leuu-Arg(Pbf)-Pro-Gly-NH2
11.Deprotection of side chains from Protected Triptorelin
Crude Triptorelin
12.Purification
Triptorelin phosphate
13.Desalting and purification
Triptorelin Acetate
14.Final filtration and freeze drying
p-Glu-His-Trp-ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2
(Triptorelin)
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
15. Manufacturing Process of Other Proposed Peptide
Peptide Synthesis is done by coupling of protected amino acids, forming peptide chain on Resin
Clevage/ TFA Clevage of synthesized Peptide from Resin
Crude Peptide is obtained that needs Purification
Purification of crude peptide by HPLC
Concentration of purified peptide by reverse osmosis/Rotary evaporator followed by filtration for freeze drying
Freeze drying of concentration, filtered peptide to obtain final product in powder form
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
16. Manufacturing Process of Oxytocin
Benzyl Chloroformate Alkali
Leucine Protected Leucine
Protected Leucine Glycine Ethly Ester
Protected Dipeptide ester
HBr in AcOH/ether Protected Dipeptide ester Free Dipeptide Ester Or Cacalytic hydrogenated
Protected Proline Free Dipeptide Ester Protected Dipeptide ester Active ester
Methanol and Ammonia Free Dipeptide Ester Protected Dipeptide ester
Benzene Chloroformate Thio Protected Cysteine Amino & Thio Protected Alkal Cysteline
p-Nitro Phenol Protected Amino Acids Protected Amino acids Dicyclohexyl Carbodimide active esters
HBr in AcOH/ ether Protected Tripeptide amide Free Tripeptide Amide Or Catalytic hydrogenation
1 HBr in AcOH/ Protected Tetrapeptide ether Free Tetrapeptide
Free Tetrapeptide Protected Asparagine Active ester
Protected Pentapeptide
HBr in AcOH/ ether Protected Pentapeptide Free Pentapeptide
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
Free Pentapeptide Protected Pentapeptide
Protected Hexapeptide
Amino and Thio Protected Tyrosine ethyl ester
cysteine
Dicyclohexyl carbodiimide
Protected Dipeptide ester
Protected Dipeptide ester
Hydrazine Hydrate
Azide (Not isolated)
HBr in AoCH/ether Protected Hexapeptide Free Hexapeptide
Benzene Chloroformate Protected tri peptide Azide (not isolated)
hydrazine
Azide Free Hexapeptide
Protected Nonapeptide
Sodium LiquidAmmonia Protected Nonapeptide Free Nonapeptide Reduction
Free Nonapeptide
Crude Oxytocin
Oxytocin solution
Reverse Osmosis
M/s. Hemmo Pharmaceuticals Pvt. Ltd.
HPCL Purification
Freeze Drying
Oxytocin Powder
Oxytocin solution