Crystallization-induced asymmetric transformations (CIAT): stereoconvergent acid-catalyzed lactonization of substituted 2-amino-4-aryl-4-hydroxybutanoic acids

Berkeš, Dušan; Kolarovič, Andrej; Manduch, Robert; Baran, Peter; Považanec, František

doi:10.1016/j.tetasy.2005.04.024

Cited by 36 publications

(22 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If the first, rate-determining step is the conjugate addition, by analogy with the findings of David or Berkes, the aza-Michael reaction should occur regioselectively at position C-2 to afford pyrrolidin-3-one 5 as the result of subsequent cyclisation. [18,19] In our hands this same C-2 selectivity was confirmed by the regioselective reaction of benzylamine with ethyl 3-acetylacrylate (2a). From this observation, path a (Scheme 4) implying C-3 regioselectivity can therefore be discarded.…”

Section: Resultssupporting

confidence: 59%

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

2006

View full text Add to dashboard Cite

We report a one-pot methodology for the synthesis of N-alkylated 2-substituted azetidin-3-ones based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates, obtained in turn in three steps from levulinic acid. IntroductionSince the azetidin-3-one core has been used as a precursor for the synthesis of the natural sphingosine-type alkaloids penaresidines A and B and penazetidin A, [1] or as an intermediate in the synthesis of polyoxin antibiotics, [2,3] a number of different methodologies to obtain these fourmembered heterocycles have previously been described. [4] Cyclisation based on rhodium carbenoid intramolecular NH insertion has been developed by Seebach for the preparation of some azetidine-containing amino alcohol and amino acid derivatives [5] and by Vederas et al. for the synthesis of keto-glutamine analogues, [6] while De Kimpe has recently reported the synthesis of 4-alkyl-1-benzhydryl-2-(methoxymethyl)azetidin-3-ol as the result of stereoselective alkylation at the C-4 position of the corresponding azetidin-3-one obtained through a high-temperature reaction of an N-(diphenylmethylidene)-3-bromoamine precursor. [7] Azetidin-3-ones could also be obtained from the corresponding azetidin-3-ol precursors by use of pyridinium dichromate or Swern-type oxidation conditions. [8] As part of a recently started program aiming at the transformation of non-food/non-feed agricultural products, byproducts and waste materials into commodity chemicals we were interested in fine chemistry application of polyfunctionalised building blocks. One such derivative is 4-oxopentanoic acid or levulinic acid (LA; 1), traditionally obtained through the controlled degradation of hexose sugars by mineral acids.[9] The increasing number of patents directed towards the production of levulinic acid demonstrates its potential as an important basic chemical that could now be cost-efficiently produced from raw materials such as wood, [a] 2440A mechanistic interpretation of these reactions and an attempted enantioselective approach are also described. Germany, 2006) starch, cellulose-containing waste materials, recycled paper, or agricultural residues.[10]Beside its conversion into methyltetrahydrofuran, a fuel extender, or into δ-aminolevulinic acid, a biodegradable broad spectrum herbicide, [11] levulinic acid (1) also offers a great number of other synthetic transformations, [12] such as the synthesis of fused heterocycles prepared from norbornane amino acids and diamines [13] or the synthesis of the antibiotic lissoclinolide. [14] For a recent synthetic endeavour we needed ethyl 5-bromo-4-oxopent-2-enoate (3a) as key intermediate. This levulinic acid derivative appeared to be an even more versatile intermediate for further transformations such as Diels-Alder reactions, coupling reactions, nucleophilic substitutions and conjugate additions, and it was speculated that nucleophilic substitution combined with intramolecular Michael reaction should ope...

show abstract

Section: Resultssupporting

confidence: 59%

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

2006

View full text Add to dashboard Cite

show abstract

“…20 From the same oxoaminoacids 3 and ent-3, the acidcatalysed lactonisation of the mixture of syn-and anti-c-aryl-chydroxy-a-amino acids, via a second CIAT process (step c), Scheme 2), produced cis-butano-4-lactones 5 and ent-5 in high yield and diastereoselectivity. 21 Both lactones were converted to the syn-and anti-HPA-12 derivatives via lactone reduction, Ndebenzylation and acylation (steps d-f), Scheme 2). 14a Overall, starting from 7 g of (E)-4-oxo-4-phenylbut-2-enoic acid (2), yielding 10 g of the corresponding oxoamino acids 3 (3 and ent-3), the stereodivergent synthesis of both syn-and anti-HPA-12 and their enantiomers produced ca.…”

Section: Resultsmentioning

confidence: 99%

The CERT antagonist HPA-12: First practical synthesis and individual binding evaluation of the four stereoisomers

Santos

Fleury

Rodriguez

et al. 2015

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

“…aza-Michael addition to aroyl-and heteroaroyl acrylic acids [6,7,15,22,23,25]. In all experiments the experimental claim that the major diastereomer of (S)-PEA addition elutes first under the respective HPLC conditions and the major diastereomer from (R)-phenylglycinol addition elutes the second one was confirmed.…”

Section: Aza-michael Addition Synthesis Of Oxoaminoacids 5-8mentioning

confidence: 56%

“…Several naturally occurring acylacrylic acids show notable antibiotic activity [4,5]. Moreover as we have demonstrated in our recent papers the aroyl- [6] or heteroaroylacrylic [7] acids are a useful synthons for the preparation of γ-oxo-and γ-hydroxysubstituted α-amino acids and acylacrylic subunit appears to have a broad potential as a crystallization-induced asymmetric transformation (CIAT) template [8,9].…”

Section: Introductionmentioning

confidence: 99%

Indolyl substituted 4-oxobut-2-enoic acids. Synthesis and aza-Michael additions

et al. 2007

Self Cite

View full text Add to dashboard Cite

Abstract:The synthesis of three new substituted 4-hetereoaryl-4-oxobut-2-enoic acids with indole ring substitutedin positions 3-, 5-and 7-is described. The addition of these Michael acceptors to 4-(1-phenylsulphonylpyrrol-3-yl)-4-oxobut-2-enoic acid in conjugate addition was explored using both racemic and chiral amines. In tandem with the crystallization-induced asymmetric transformation (CIAT) protocol the effective methodology for the synthesis of enantiomerically highly enriched substituted 2-amino-4-heteroaryl-4-oxobutanoic acids as multifunctional homotryptophan analogues was developed.

show abstract

Crystallization-induced asymmetric transformations (CIAT): stereoconvergent acid-catalyzed lactonization of substituted 2-amino-4-aryl-4-hydroxybutanoic acids

Cited by 36 publications

References 28 publications

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

The CERT antagonist HPA-12: First practical synthesis and individual binding evaluation of the four stereoisomers

Indolyl substituted 4-oxobut-2-enoic acids. Synthesis and aza-Michael additions

Contact Info

Product

Resources

About