N-substituted hydroxysuccinimides from (s)-malic acid as new reagents for asymmetric diels-alder additions to enoates

Poll, Thomas S. van der; Hady, A. F. Abdel; Karge, Reinhard; Linz, G.; Weetman, J.; Helmchen, Günter

doi:10.1016/s0040-4039(01)93808-0

Cited by 58 publications

(18 citation statements)

References 6 publications

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“…Precursor 9 was prepared according to Poll 24 and Fukaya. 25 To a solution of ethyl chloroformate (2.04 mL, 21.4 mmol) in hexane (20 mL) was added dropwise a solution of 9 (3.0 g, 21.4 mmol) and triethylamine (3.07 mL, 22 mmol) in hexane (20 mL) at 0 °C.…”

Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

et al. 2013

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CaV1.3 L-type calcium channels (LTCCs) have been a potential target for Parkinson’s disease since calcium ion influx through the channel was implicated in the generation of mitochondrial oxidative stress, causing cell death in the dopaminergic neurons. Selective inhibition of CaV1.3 over other LTCC isoforms, especially CaV1.2, is critical to minimize potential side effects. We recently identified pyrimidinetriones (PYTs) as a CaV1.3-selective scaffold; here we report the structure-activity relationship of PYTs with both CaV1.3 and CaV1.2 LTCCs. By variation of the substituents on the cyclopentyl and arylalkyl groups of PYT, SAR studies allowed characterization of the CaV1.3 and CaV1.2 LTCCs binding sites. The SAR also identified four important moieties that either retain selectivity or enhance binding affinity. Our study represents a significant enhancement of the SAR of PYTs at CaV1.3 and CaV1.2 LTCCs and highlights several advances in the lead optimization and diversification of this family of compounds for drug development.

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Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

et al. 2013

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“…The enantioselective hydrogenation 81,82 of pyrrolidine-2,3,5-triones 112 over chirally modified Pt afforded cyclic alcohols 113, very useful chiral auxiliaries for Lewis acidcatalyzed enantioselective Diels-Alder reactions of enolates 83 (Scheme 34). A series of 1-and 4-substituted pyrrolidine-2,3,5-triones was prepared via two routes 11,19 starting from racemic lactones (Scheme 3), or from corresponding acetamide derivatives (Scheme 2).…”

Section: Hydrogenation Of Pyrrolidine-235-trionesmentioning

confidence: 99%

Pyrrolidinetrione Derivatives: Synthesis And Applications in Heterocyclic Chemistry

Zaleska¹,

Lis²

2001

Synthesis

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This review article, covering the literature from 1891 to 1999, deals with the methods of preparation of pyrrolidinetrione derivatives, emphasis being placed on methods of reasonable efficiency. A general applicability of these compounds as versatile building blocks in synthesis of fused heterocyclic systems is in focus. Pyrrolidine-2,3,4-trione Derivatives in the Synthesis of Anellated Nitrogen-Containing 5,5-Ring Systems 4 Hydrogenation of Pyrrolidine-2,3,5-triones 5 Su mmary

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“…3 is an asymmetric Diels-Alder reaction catalyzed by chiral nonracemic catalysts. 3,4 Since it is very hard to get the Diels-Alder products in optically pure forms, enantiomeric enhancement such as recrystallization, etc., is usually necessary to obtain the optically pure methylnorbornene aldehyde. In 1a's case, 1a is an oil and we prepared the optically pure 1a in a three-step sequence including recrystallization of the asymmetric Diels-Alder reaction product (90% de): 1) asymmetric Diels-Alder reaction of the commercially available N-crotonyl-(4S)-isopropyl-2-oxazolidinone and cyclopentadiene according to Evans' method 1 ; 2) LiAlH 4 reduction in THF at room temperature (97%) after obtaining the optically pure amide by recrystallization; and 3) the Swern oxidation (73%) (Eq.…”

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confidence: 99%

Kinetically controlled optical resolution of racemic norbornene aldehyde derivatives

et al. 2002

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A new method for obtaining optically pure 5-norbornene 2-endo-aldehyde derivatives was developed. The reaction of a diastereomeric mixture of the ene acetals 2 and 2', derived from racemic norbornene aldehydes (+/-)-1 and chiral nonracemic (S,S)-hydrobenzoin 7, with NBS (0.5-0.6 eq.) in the presence of H(2)O proceeded in a kinetically controlled manner to give the optically pure hydroxy aldehydes 3 along with the intact ene acetals 2'. Both compounds 3 and 2' were converted into the optically pure norbornene aldehydes 1 and ent-1, respectively. This method opens the way to produce various types of 5-norbornene 2-endo-aldehydes with 3-exo- or 3-endo-substituents in optically pure forms.

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N-substituted hydroxysuccinimides from (s)-malic acid as new reagents for asymmetric diels-alder additions to enoates

Cited by 58 publications

References 6 publications

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

Pyrrolidinetrione Derivatives: Synthesis And Applications in Heterocyclic Chemistry

Kinetically controlled optical resolution of racemic norbornene aldehyde derivatives

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N-substituted hydroxysuccinimides from (s)-malic acid as new reagents for asymmetric diels-alder additions to enoates

Cited by 58 publications

References 6 publications

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as CaV1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as CaV1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

Pyrrolidinetrione Derivatives: Synthesis And Applications in Heterocyclic Chemistry

Kinetically controlled optical resolution of racemic norbornene aldehyde derivatives

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Product

Resources

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Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease

Structure–Activity Relationship of N,N′-Disubstituted Pyrimidinetriones as Ca_V1.3 Calcium Channel-Selective Antagonists for Parkinson’s Disease