An object of the present invention is to provide a lactone compound having excellent water stability.

Provided is a lactone compound represented by Formula (I).

##STR00001##

In Formula (I), R.sup.1 and R.sup.2 each independently represent a substituent which does not have a dissociative proton and has a Hammett's substituent constant σp value of −0.90 or more and −0.03 or less. R.sup.3 represents a substituent which does not have a dissociative proton and has a Hammett's substituent constant σp value of −0.90 or more and −0.03 or less, or a hydrogen atom. Y represents a substituent and n represents an integer of 1 to 4. In a case where n is an integer of 2 to 4, a plurality of Y's may be the same substituent or substituents different from each other.

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): ##STR00001##
or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q.sub.1, Q.sub.2, Z, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.

The present disclosure pertains to a new synthetic method for the preparation of 3,6-dimethylhexahydrobenzofuran-2-one, a derivative of mint lactone, and an important organoleptic compound which finds use in the flavor and fragrance industries. Applicants' novel synthetic route is also applicable to other alkene compounds.

The present disclosure pertains to a new synthetic method for the preparation of 3,6-dimethylhexahydrobenzofuran-2-one, a derivative of mint lactone, and an important organoleptic compound which finds use in the flavor and fragrance industries. Applicants' novel synthetic route is also applicable to other alkene compounds.

A monomer represented by Chemical Formula 1:

##STR00001##

wherein, in Chemical Formula 1, R.sup.1, R.sup.2, A.sup.1, A.sup.2, L.sup.1, L.sup.2, o, p, q, and r are the same as defined in the detailed description.

Provided is a method for purifying waste N-methyl-2-pyrrolidone, the method comprising the steps of: reacting the waste N-methyl-2-pyrrolidone containing an amine compound with an acid anhydride; converting the amine compound into an amide compound; and removing the amide compound by distillation, thereby manufacturing high-purity N-methyl-2-pyrrolidone that can be reused.

Provided is a method for purifying waste N-methyl-2-pyrrolidone, the method comprising the steps of: reacting the waste N-methyl-2-pyrrolidone containing an amine compound with an acid anhydride; converting the amine compound into an amide compound; and removing the amide compound by distillation, thereby manufacturing high-purity N-methyl-2-pyrrolidone that can be reused.

A process for the synthesis of trans-fused γ-lactones having Formula (IV) from substituted cyclic ketones having Formula (I). A diastereoselective synthesis of (±)-epianastrephin (1) (wherein: R.sup.1 is ethenyl, R.sup.2 and R.sup.3 is methyl, and n is 1), (±)-anastrephin (2) (wherein: R.sup.2 is ethenyl, R.sup.1 and R.sup.3 is methyl and n is 1), and analogs thereof (wherein: R.sup.1 is H, C.sub.1-5 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, R.sup.2 is H, C.sub.1-5 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, R.sup.1 and R.sup.2 together with the carbon atom they are attached form a C.sub.3-6 cycloalkyl ring, R.sup.3 is C.sub.1-5 alkyl and n is 0-2):

##STR00001##

A process for the synthesis of trans-fused γ-lactones having Formula (IV) from substituted cyclic ketones having Formula (I). A diastereoselective synthesis of (±)-epianastrephin (1) (wherein: R.sup.1 is ethenyl, R.sup.2 and R.sup.3 is methyl, and n is 1), (±)-anastrephin (2) (wherein: R.sup.2 is ethenyl, R.sup.1 and R.sup.3 is methyl and n is 1), and analogs thereof (wherein: R.sup.1 is H, C.sub.1-5 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, R.sup.2 is H, C.sub.1-5 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, R.sup.1 and R.sup.2 together with the carbon atom they are attached form a C.sub.3-6 cycloalkyl ring, R.sup.3 is C.sub.1-5 alkyl and n is 0-2):

##STR00001##

Compounds of formula (I) ##STR00001##
and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein R.sup.1, Z.sup.1, Z.sup.2, and n are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by Tropomysin receptor kinases (Trk). Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.