Reduction of (-)-R-carvone (I) with LiAlH4 in Et2O at -78 C gave alcohol (II). Inversion of the hydroxyl group was then achieved by Mitsunobu reaction with 4-nitrobenzoic acid (III), followed by hydrolysis of the resulting 4-nitrobenzoate ester (IV) to give (V). Treatment of alcohol (V) with ethyl vinyl ether (VI) and N-bromosuccinimide produced the bromoacetal (VII). Subsequent intermolecular radical cyclization of (VII) with NaBH4 in the presence of a catalytic amount of Bu3SnCl and AIBN yielded cyclic acetal (VIII). Acidic hydrolysis of (VIII) followed by reduction of the resulting aldehyde (IX) with LiAlH4 provided diol (X). Protection of the primary alcohol group with trityl chloride in the presence of DMAP gave (XI), and subsequent oxidation of the secondary alcohol with pyridinum chlorochromate afforded ketone (XII). Further carbomethoxylation of (XII) by treatment with LDA and methyl cyanoformate yielded ketoester (XIII), which was reduced to alcohol (XIV) with NaBH4 in MeOH at 0 C. Then, alcohol (XIV) was converted to methyl ether (XV) by reaction with methyl iodide and NaH in DMF, and the ester group was reduced to alcohol (XVI) with LiAlH4 in Et2O at 0 C. Alcohol (XVI) was converted to mesylate (XVII) with methanesulfonyl chloride and Et3N.

Reaction of mesylate (XVII) with triazole sodium salt (XVIII) gave (XIX). Ozonization of olefinic double bond, followed by treatment with Me2S and K2CO3 provided ketone (XX). Then, haloform reaction with NaOBr gave acid (XXI), and reduction with LiAlH4 in cold Et2O afforded primary alcohol (XXII). Alcohol (XXII) was converted to mesylate (XXIII), and this was condensed with 4-(trifluoromethoxy)phenol (XXIV) to give ether (XXV). Deprotection of the trityl group with formic acid in EtOAc and subsequent reaction with methanesulfonyl chloride provided mesylate (XXVI), which was finally condensed with mercaptoimidazole (XXVII) to furnish the target compound.

Reduction of (-)-R-carvone (I) with LiAlH4 in Et2O at -78 C gave alcohol (II). Inversion of the hydroxyl group was then achieved by Mitsunobu reaction with 4-nitrobenzoic acid (III), followed by hydrolysis of the resulting 4-nitrobenzoate ester (IV) to give (V). Treatment of alcohol (V) with ethyl vinyl ether (VI) and N-bromosuccinimide produced the bromoacetal (VII). Subsequent intermolecular radical cyclization of (VII) with NaBH4 in the presence of a catalytic amount of Bu3SnCl and AIBN yielded cyclic acetal (VIII). Acidic hydrolysis of (VIII) followed by reduction of the resulting aldehyde (IX) with LiAlH4 provided diol (X). Protection of the primary alcohol group with trityl chloride in the presence of DMAP gave (XI), and subsequent oxidation of the secondary alcohol with pyridinum chlorochromate afforded ketone (XII). Further carbomethoxylation of (XII) by treatment with LDA and methyl cyanoformate yielded ketoester (XIII), which was reduced to alcohol (XIV) with NaBH4 in MeOH at 0 C. Then, alcohol (XIV) was converted to methyl ether (XV) by reaction with methyl iodide and NaH in DMF, and the ester group was reduced to alcohol (XVI) with LiAlH4 in Et2O at 0 C. Alcohol (XVI) was converted to mesylate (XVII) with methanesulfonyl chloride and Et3N.

Reaction of mesylate (XVII) with triazole sodium salt (XVIII) gave (XIX). Ozonization of olefinic double bond, followed by treatment with Me2S and K2CO3 provided ketone (XX). Then, haloform reaction with NaOBr gave acid (XXI), and reduction with LiAlH4 in cold Et2O afforded primary alcohol (XXII). Alcohol (XXII) was converted to mesylate (XXIII), and this was condensed with 4-(trifluoromethoxy)phenol (XXIV) to give ether (XXV). Deprotection of the trityl group with formic acid in EtOAc and subsequent reaction with methanesulfonyl chloride provided mesylate (XXVI), which was finally condensed with morpholine (XXVII) to furnish the target compound.