Fresenius Kabi Ipsum S.r.l.

Alma Mater Studiorum-Universitá Di Bologna

Fresenius Kabl Ipsum S.r.l.

Antonio Ricci

Walter Cabri

Jacopo Zanon

Andrea Orlandin

Saswata Lahiri

Timo Nuijens

Govind Singh

Ana Toplak

Ivan Guryanov

Nitin Kumar

Fernando Formaggio

Shivaji Haribhau Shelke

Madan Singh

Barbara Biondi

Dario Visentini

Alessandra Tolomelli

Lucia Ferrazzano

Shridhar Reddy

Dominik Heckmann

Steve McIntyre

Alex Saunders

Paolo Cantelmi

Giulia Martelli

Chiara Palladino

Marco Macis

Angelo Viola

Giuseppina Maria Incisivo

Tapanjyoti Biswal

Rowin De Visser

Kerstin Wallraven

Elvira Wijker

Alice Pozzebon

Andrea Borgogno

Jurgen Mateman

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.

Process for the manufacture of degarelix and its intermediates

The invention provides a method for the cleavage of Fmoc group characterized by using a solution comprising 3-(diethylamino)propylamine. In particular, it provides a method for the preparation of peptides in solid phase wherein Fmoc protected amino acids are used and the Fmoc group is cleaved by a solution comprising 3-(diethylamino)propylamine.

Amino deprotection using 3-(diethylamino)propylamine

The present invention provides an improved process for the preparation of high purity glucagon comprising the use of Xmb-protected amino acids, wherein may Xmb include, e.g., 2,4,6-trimethoxybenzyl, 2,4-dimethoxybenzyl, or 2-hydroxy-4-methoxybenzyl. The process also comprises the use of building blocks such as pseudoprolines to avoid aggregation and obtain the product in high yield and purity.

Process for the preparation of high purity glucagon

The present invention provides a process for the manufacture of GLP-1 analogues with high yield and purity by fragment condensation on the solid phase. In particular, it describes a convergent synthesis by condensation of a C-terminal pseudoproline fragment A with a fragment B bound to a solid support, followed by deprotection and cleavage from the support and final purification to yield the desired peptide. The invention further provides intermediates useful in the manufacturing process.

Process for the manufacture of GLP-1 analogues

The present application provides an improved process for the preparation of sugammadex by reacting a salt of 3-mercapto propionic acid with 6-per-deoxy-6-per-halo-&#x3b3;-cyclodextrin in a suitable organic solvent. This application also provides crystalline form of a salt of 3-mercapto propionic acid, preferably di sodium salt of 3-mercapto propionic acid and its use for the preparation of sugammadex, whereas formula (I) shows the sodium salt of sugammadex.

Process for the preparation of sugammadex

The present application provides crystalline forms of 6-per-deoxy-6-per-chloro-&#x3b3;-cyclodextrin, and polymorphs thereof. The present application also provides methods for preparing said polymorphs by dissolving 6-per-deoxy-6-per-chloro-&#x3b3;-cyclodextrin in dimethylformamide and using an anti-solvent of a water/alcohol mixture.

Crystalline forms of per-chloro-&#x3b3;-cyclodextrines

The present application provides an improved process for the preparation of sugammadex which comprises the halogenation of &#x3b3;-cyclodextrin in a suitable organic solvent to give 6-per-deoxy-6-per-halo-&#x3b3;-cyclodextrin, wherein halo is bromo or chloro, reacting the halogenated &#x3b3;-cyclodextrin with 3-mercaptopropionic acid in the presence of alkoxide base to obtain sugammadex of formula I. This application also provides isolation of 6-per-deoxy-6-per-chloro-&#x3b3;-cyclodextrin as a crystalline compound and its use for the preparation of sugammadex of formula (I).

Process for the preparation of sugammadex and its intermediates

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Pescara, Italy

Antonio Ricci