Usv Private Limited

Nilesh Dagdu Patil

Divya Lal Saksena

Chandrakesan Muralidharan

Nikhil Umesh Mohe

Lester John Lobo

Digamber Shripati Pawar

Rakesh Shekhawat

Shrikant Mishra

Sagar Satyanarayan Zawar

Radhakrishnan Venkatasubramanian Tarur

Dinesh Kumar Paliwal

Mandar Ravindra Maduskar

Radharkrishnan Venkatsubramanian Tarur

Aruna Khare

Pankaj Prabhakar Malpure

Dilip Kumar Rana

This invention relates a process for preparing octreotide and derivatives thereof. The starting material, Cys(Trt)-2-Chlorotrityl resin is coupled with various amino acids to obtain a protected heptapeptide of formula (2): Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-2-Chlorotrityl resin. The linear protected peptide of formula (2) is cleaved from the support using TFA5TIS and water to yield linear protected peptide of formula (3) Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-OH Linear protected heptapeptide of formula (3) is deprotected to yield heptapeptide of formula (6): D-Phe-Cys-Phe-D-Tip-Lys-Thr-Cys-OH; which is cyclized using hydrogen peroxide and to the cyclic peptide of formula (7) D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-OH; threoninol is coupled at C terminal to yield octreotide. Alternatively threoninol is coupled to the heptapeptide of formula (3) to yield protected octapeptide of formula (4) Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-Thr-OL which is subsequently deprotected to yield linear octapeptide of formula (5) D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OL and cyclized with hydrogen peroxide to yield cyclic octreotide with a yield of &#x3e;95%. 

Process for synthesis of cyclic octapeptide

The present invention relates to an improved process for the preparation of N-(aminoiminomethyl)-N-(3-mercapto-1-oxopropyl)-L-lysylglycyl-L-&#x3b1;-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic(1&#x2192;6)-disulfide of formula (1), which involves assembling a peptide chain comprising of six amino acids and a thioalkyl carboxylic acid in a required sequence on a solid support to obtain a peptide bound resin of formula (2), capping the free amino groups after each coupling, cleaving Dde group in the peptide of formula (2) from the solid support to obtain peptide-solid support of formula (3), guanylating the peptide of formula (3) at &#x3b5;-lysine-NHin an organic solvent to obtain peptide-solid support of formula (4), cleaving and deprotecting all groups in the peptide of formula (4) from the solid support to obtain peptide-amide formula (5), oxidizing the SH-peptide of formula (5) with an appropriate oxidizing agent to obtain the crude peptide-amide of formula (1) and purifying the crude peptide-amide of formula (1) by chromatographic technique. The solid support is either resin or a cellulose support like cotton, gauze, fabric, paper and perloza beads. The described process is simple, easy, environment friendly, takes lesser time and more cost effective.

Solid phase Fmoc chemistry process to prepare peptides

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Mumbai, India

Nilesh Dagdu Patil