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

A three-step one-pot synthesis of various target compounds (IV), (VI), (VIII), (X), (XII), and (XIV) is presented.

Transformations of Enaminones. A Simple One-Pot Synthesis of Imidazolone Derivatives.

A library of twelve N(4′)-substituted di-tert-butyl (2S,4E)-4-arylaminomethylidene-5-oxopyrrolidine-1,2-dicarboxylates 6/6′a – l were prepared in 47 – 90 % yield by parallel acid-catalysed treatment of di-tert-butyl (2S,4E)-4-[(dimethylamino)methylidene]-5-oxopyrrolidine-1,2-dicarboxylate (4) with anilines 5a – j, ethyl glycinate (5k), and ethyl β -alaninate (3l). Acidolytic deprotection of compounds 6a – c, e – j afforded the corresponding (2S,4E)-4-arylaminomethylidene-5-oxopyrrolidine-2-carboxylic acids 7a – c, e – j in 39 – 99 % yield. The configuration around the C=C double bond in the enaminones 6 and 7 was determined by NMR spectroscopy.

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Parallel Solution-phase Synthesis of (2S,4E)-4-(Arylaminomethylidene)pyroglutamic Acids

Azatryptophane homologues, 4-(imidazo[1,2-a]pyridinyl-3)- 9a-9f and 4-(imidazo[1,2-a]pyrimidinyl-3)-4-oxohomoalanine derivatives 9g-91, were prepared from N,N-dimethyl-N′-(pyridinyl-2)- 6a-6f and N,N-dimethyl-N-(pyriniidinyl-2)formamidines 6g-6i, and (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester (2) and its (R,S)-isomer.

The Synthesis of Azahomotryptophane Derivatives. The Transformation of N-Trifluoroacetyl-5-bromo-4-oxonorvaline Methyl Ester into 4-(Imidazo[1,2-a]azinyl-3)-4-oxohomoalanine Derivatives.

The transformations of imidazolidinedione derivatives (I) and (VIII) with dicarbonyl compounds like (II) and (IX) into pyrano[2,3-d]pyrimidine (V) and chromene (X) derivatives are described.

Transformations of dimethyl (2E,3E)-2-〔(dimethylamino)methylene〕-3-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate with C-nucleophiles

Pyrrole is an important heterocycle because its structure is incorporated in a variety of biologically important compounds, such as heme, chlorophyll, vitamin B12, and bile pigments. Besides, pyrrole and pyrrolidine partial structures occur in numerous natural products and synthetically important compounds [1]. Among numerous syntheses of pyrroles reported so far in the literature, three general methods have to be outlined: a) the Paal-Knorr synthesis of pyrroles from 1,4-dicarbonyl compounds and primary amines (5+1 cyclocondensation approach), b) the Knorr pyrrole synthesis from α-amino ketones and 1,3-dicarbonyl compounds (3+2 cyclocondensation approach), and c) the van Leusen synthesis of pyrroles from tosylmethyl isocyanide (Tosmic) and α ,β -unsaturated carbonyl compounds (3+2 cycloaddition approach) [1]. 2-Substituted alkyl 3-(dimethylamino)prop-2enoates and related enaminones are a group of enamino-masked alkyl α-formylacetates, which are easily available and are versatile reagents in heterocyclic synthesis [2]. In addition to their extensive use in the synthesis of various heterocyclic systems, recent applications of enaminones are mostly oriented towards the preparation of functionalised heterocyclic compounds including natural product analogues [2 – 4] and in combinatorial synthesis of functionalized heterocycles [5]. In this context, pyrrole derivatives have been prepared by intramolecular cyclisation of 2-(2-cyano-vinyl)amino-3-(dimethylamino)

Branko Stanovnik

Papers

Transformations of Enaminones. A Simple One-Pot Synthesis of Imidazolone Derivatives.

Parallel Solution-phase Synthesis of (2S,4E)-4-(Arylaminomethylidene)pyroglutamic Acids

The Synthesis of Azahomotryptophane Derivatives. The Transformation of N-Trifluoroacetyl-5-bromo-4-oxonorvaline Methyl Ester into 4-(Imidazo[1,2-a]azinyl-3)-4-oxohomoalanine Derivatives.

Transformations of dimethyl (2E,3E)-2-〔(dimethylamino)methylene〕-3-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)succinate with C-nucleophiles

A Simple Synthesis of 1‐Substituted Diethyl Pyrrole‐3,4‐dicarboxylates.