The present invention relates to the processes for preparing glucagon-like peptide-1 (glp-1) receptor agonists and their analogs. The present invention further relates to processes for preparing liraglutide, D-liraglutide, semaglutide and D-semaglutide. The present invention specifically relates to processes for preparing glucagon-like peptide-1 (glp-1) agonist and their analogs, wherein the liraglutide, D-liraglutide, semaglutide and D-semaglutide produced are substantially pure. The present invention also relates to preparation of glucagon-like peptide-1 (glp-1) agonist and their analogs by solid and solution phase method.

In a preferred embodiment, there is provided a protecting group for protecting the thiol side chain of a cysteine residue, the protecting group comprising a Diels-Alder cycloadduct of a furan and a maleimide, and optionally, a linker interposed between the thiol side chain and the Diels-Alder cycloadduct.

Methods for preparing degarelix acetate are provided that include the steps of providing a suitable resin; deprotecting the resin with a diethylenetriamine solution; reacting sequentially the deprotected resin with different Fmoc protected amino acids; deprotecting the amino acid in each sequence with a diethylenetriamine solution in a stepwise fashion to yield a degarelix crude compound; and purifying the degarelix crude compound to yield pharmaceutically acceptable degarelix acetate. Methods of preparing degarelix acetate-mannitol premix and the resulting degarelix acetate-mannitol premix are also provided.

The present invention comprises compounds of Formula I. ##STR00001## wherein: Z.sub.4, Z.sub.7, Z.sub.9, Z.sub.11, Z.sub.22, Z.sub.23, Z.sub.26, Z.sub.30, Z.sub.34, Z.sub.35, p, m, n, q, and BRIDGE are defined in the specification. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel compounds are useful for preventing, treating or ameliorating diseases and disorders, such as obesity, type 2 diabetes, the metabolic syndrome, insulin resistance, and dyslipidemia, among others.

The present inventors found that peptide compounds/amide compounds in which the protecting groups of interest are removed and/or which are removed from resins for solid-phase synthesis can be produced without main chain damage by contacting starting peptide compounds/amide compounds with silylating agents.

The present inventors found that peptide compounds/amide compounds in which the protecting groups of interest are removed and/or which are removed from resins for solid-phase synthesis can be produced without main chain damage by contacting starting peptide compounds/amide compounds with silylating agents.

The invention relates to a method for preparing peptides comprising the step of forming a peptide bond wherein the carboxyl group of a first amino acid or first peptide is activated and an amino group of the first activated amino acid or first peptide is protected by a protecting group having a water-solubility enhancing group and the activated carboxyl group of the first amino acid or first peptide is reacted with an amino group of a second amino acid or second peptide wherein said carboxyl group of the first amino acid or first peptide is activated in the absence of the second amino acid or second peptide. The invention further relates to peptides comprising a protecting group having a water-solubility enhancing group being bound to the amino group and an activated or free carboxyl group.

There is provided an α-carbonyl alkenyl ester and a preparation method therefor, and the α-carbonyl alkenyl ester is further used to react with a primary or secondary amine to prepare an amide. The two reactions are combined to develop an amide bond and peptide bond formation method that directly use carboxylic acids and amines as starting materials and allenones as a condensing reagent. The α-carbonyl alkenyl ester corresponding to an α-amino acid serves as a peptide synthesis building block and is used in solid phase peptide synthesis. The method is carried out under mild reaction conditions, simple to operate, and has a high yield. Compared with existing amide bond condensation reagents, the allenones have the advantages of being simple to prepare, having good stability, a low molecular weight, not racemizing when activating α-chiral carboxylic acids, and is a novel amide bond and peptide bond condensing reagent.

The disclosure provides a method for preparing drug-linker MC-MMAF for antibody drug conjugates and intermediates therein. The preparation method of the present disclosure improves the reactivity of the N-terminal, thereby effectively controlling the occurrence of racemization; does not directly use the toxin MMAF, but uses fragmented peptides with lower toxicity, which minimizes the operational difficulty in scale-up production; no reverse phase is required and it is easy to prepare and operate.

A peptide having a fluoroalkyl group as its side chain and a method for producing, which comprises condensing a compound represented by the formula (6-2) or (6-4), where means that an asymmetric carbon atom has an absolute configuration of S or R, Rf is a C.sub.1-30 alkyl group which is substituted with at least two fluorine atoms, and which may further be substituted with a halogen atom other than a fluorine atom (when the C.sub.1-30 alkyl group is a C.sub.2-30 alkyl group, it may have 1 to 5 etheric oxygen atoms between carbon atoms), and R.sup.2 is a protecting group for the amino group, with a fluorinated amino acid having its carboxy group protected, an amino acid having its carboxy group protected, a fluorinated peptide having its C-terminal protected, or a peptide having its C-terminal protected.