Asymmetric 1,3-Dipolar Cycloaddition Reactions

Chem. Pharm. Bull.(オピニオン)

Recent developments in the chemistry of enaminones

Synthesis of heterocycles from alkyl 3-(dimethylamino)propenoates and related enaminones.

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: 
wherein M is N or CR 4 ; Q 1 and Q 2 are each independently selected from the group consisting of CO, SO, SO 2 , and C═NR 9 ; and each L, X, R 1 , R 2 , and R 3 are as defined herein.

Dipeptidyl peptidase inhibitors

Dimethyl 3-oxopentane-1,5-dioate (dimethyl acetone-1,3-dicarboxylate) (1) was transformed first with (hetero)arenediazonium salts 3a – j into dimethyl 2-[(hetero)arylhydrazono]pentane-1,5-dioates 4a – j followed by reaction with N,N-dimethylformamide dimethylacetal (DMFDMA) to afford, without isolation of intermediates 5a – j, dimethyl 1-(hetero)aryl-4-oxo-1,4-dihydropyridazine-3,5dicarboxylates 6a – j. An alternative method represents transformation of 1 with DMFDMA into dimethyl 2-[(dimethylamino)methylidene]-3-oxopentane-1,5-dioate (7) followed by treatment with (hetero)arenediazonium salts 3a – c, j to give pyridazine derivatives 6a – c, j.

Synthesis of Dimethyl 1-(Hetero)aryl-4-oxo-1,4-dihydropyridazine-3,5-dicarboxylates from Dimethyl 3-Oxopentane-1,5-dioates.

The opening of the pyranone ring in 2H-naphtho[1,2-b]pyran-2-one derivative (1) and 3H-naphtho[2,1-b]-pyran-3-one derivatives 8 and 20 with nucleophiles afforded 3-(naphthyl-1)- and 3-(naphthyl-2)propenoates (substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives) 7, 13, 14, 15, 24, and 35.

Transformations of Isomeric Naphthopyranones. The Synthesis of Substituted β‐Naphthyl‐α,β‐dehydro‐α‐amino Acid Derivatives.

Functionalized Enamines in the Synthesis of Some Heterocyclic Compounds.

Reaction of rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone with Aliphatic 1,3-Dicarbonyl Compounds. A ′Ring Switch′ Synthesis of rel-(2R,3R)-3-Phenyl-3-(pyrazolyl-1)alanine Esters.

Branko Stanovnik

Papers

Synthesis of Dimethyl 1-(Hetero)aryl-4-oxo-1,4-dihydropyridazine-3,5-dicarboxylates from Dimethyl 3-Oxopentane-1,5-dioates.

Transformations of Isomeric Naphthopyranones. The Synthesis of Substituted β‐Naphthyl‐α,β‐dehydro‐α‐amino Acid Derivatives.

Functionalized Enamines in the Synthesis of Some Heterocyclic Compounds.

Reaction of rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone with Aliphatic 1,3-Dicarbonyl Compounds. A ′Ring Switch′ Synthesis of rel-(2R,3R)-3-Phenyl-3-(pyrazolyl-1)alanine Esters.

Sulfur Compounds of Pyridazines