The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: ##STR00001##
where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification. The present disclosure provides a more efficient route for preparing a crystalline form of a β-turn cyclic peptidomimetic compounds and salts thereof.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: ##STR00001##
where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification. The present disclosure provides a more efficient route for preparing a crystalline form of a β-turn cyclic peptidomimetic compounds and salts thereof.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I:

##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification.

The present disclosure provides a more efficient route for preparing a crystalline form of a β-turn cyclic peptidomimetic compounds and salts thereof.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I:

##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification.

The present disclosure provides a more efficient route for preparing a crystalline form of a β-turn cyclic peptidomimetic compounds and salts thereof.

An objective of the present invention is to provide methods of producing a cyclic organic compound using a continuous stirred tank reactor(s) (CSTR), the methods being capable of achieving excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such. The present inventors conducted studies on cyclization reactions using a CSTR(s), which had not been conventionally used for cyclization reactions for cyclic compounds. As a result, the inventors have found that the present methods can achieve excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such, as compared with conventional cyclization methods. Furthermore, the present inventors have also found that the above-mentioned improvement effects can efficiently be achieved even in the production of cyclic peptides and heterocyclic compounds by applying simulation methods that had been conventionally used mainly at the fine chemicals plant level to the cyclization reactions of the present invention, thereby experimentally predicting the reaction rate of a cyclization reaction, and setting the flow volume (residence time), the concentrations of precursor and cyclic organic compound, and the temperature for the cyclization reaction and such which affect these conditions, in the cyclization reaction using a CSTR(s).

An objective of the present invention is to provide methods of producing a cyclic organic compound using a continuous stirred tank reactor(s) (CSTR), the methods being capable of achieving excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such. The present inventors conducted studies on cyclization reactions using a CSTR(s), which had not been conventionally used for cyclization reactions for cyclic compounds. As a result, the inventors have found that the present methods can achieve excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such, as compared with conventional cyclization methods. Furthermore, the present inventors have also found that the above-mentioned improvement effects can efficiently be achieved even in the production of cyclic peptides and heterocyclic compounds by applying simulation methods that had been conventionally used mainly at the fine chemicals plant level to the cyclization reactions of the present invention, thereby experimentally predicting the reaction rate of a cyclization reaction, and setting the flow volume (residence time), the concentrations of precursor and cyclic organic compound, and the temperature for the cyclization reaction and such which affect these conditions, in the cyclization reaction using a CSTR(s).

The present invention relates to a novel synthesis method to form particular molecules. These molecules have multiple uses, most notably in the field of protecting groups used throughout organic and synthetic chemistry. The disclosed method is safer, more cost- and time-effective, and more amenable to large scale production than those currently known in the art. The protecting groups synthesized are useful in GAP peptide synthesis.

The present invention relates to a novel synthesis method to form particular molecules. These molecules have multiple uses, most notably in the field of protecting groups used throughout organic and synthetic chemistry. The disclosed method is safer, more cost- and time-effective, and more amenable to large scale production than those currently known in the art. The protecting groups synthesized are useful in GAP peptide synthesis.

Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X.sup.1—S(O)(X.sup.2)F).sub.m groups attached thereto, wherein Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2; m can be 1 or 2 depending on the identity of Z; and X.sup.2 is O or NR. In some embodiments, the core group is an amino acid or a protein. In some embodiments the core group is a compound that has therapeutic activity toward a therapeutic target.

Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X.sup.1—S(O)(X.sup.2)F).sub.m groups attached thereto, wherein Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2; m can be 1 or 2 depending on the identity of Z; and X.sup.2 is O or NR. In some embodiments, the core group is an amino acid or a protein. In some embodiments the core group is a compound that has therapeutic activity toward a therapeutic target.