Stereocontrolled Synthesis of a Sphingomyelin Methylene Analogue as a Sphingomyelinase Inhibitor

Hakogi, Toshikazu; Monden, Yoshiko; Iwama, Seiji; Katsumura, Shigeo

doi:10.1021/ol006147c

Cited by 37 publications

(10 citation statements)

References 18 publications

(13 reference statements)

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“…Some synthetic substrate analogues can also be used as SMase inhibitors, e.g. a sphingomyelin methylene analogue [94], or a difluoromethylene analogue [95]. Arenz and Giannis [96] have produced the first synthetic irreversible inhibitor of nSMase.…”

Section: Sphingomyelinasesmentioning

confidence: 99%

Sphingomyelinases: enzymology and membrane activity

2002

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This paper reviews our present knowledge of sphingomyelinases as enzymes, and as enzymes acting on a membrane constituent lipid, sphingomyelin. Six types of sphingomyelinases are considered, namely acidic, secretory, Mg 2+ -dependent neutral, Mg 2+ -independent neutral, alkaline, and bacterial enzymes with both phospholipase C and sphingomyelinase activity. Sphingomyelinase assay methods and speci¢c inhibitors are reviewed. Kinetic and mechanistic studies are summarized, a kinetic model and a general-base catalytic mechanism are proposed. Sphingomyelinase^membrane interactions are considered from the point of view of the in£uence of lipids on the enzyme activity. Moreover, e¡ects of sphingomyelinase activity on membrane architecture (increased membrane permeability, membrane aggregation and fusion) are described. Finally, a number of open questions on the above topics are enunciated.

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Section: Sphingomyelinasesmentioning

confidence: 99%

Sphingomyelinases: enzymology and membrane activity

2002

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“…While the classical protocol using alkaline hypohalites is still the method of choice for simple substrates, 3,4 it often suffers from low yields, intolerance to many functional groups and side products, particularly symmetrical acyclic ureas and N-acylureas. 2 The scope of the reaction has been significantly expanded by introducing a number of more selective and efficient reagents, particularly N-bromosuccinimide (NBS), [5][6][7] 1,3-dibromo-5,5-dimethylhydantoin, 8 TsNBr 2 9 and trichloroisocyanuric acid. 10 The reaction is usually performed in alcohols, producing carbamates rather than the free amines.…”

mentioning

confidence: 99%

Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide

et al. 2016

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An efficient, one-pot procedure for the Hofmann rearrangement of aromatic and aliphatic amides has been developed. Methyl and benzyl carbamates are produced with N-bromoacetamide in the presence of lithium hydroxide or lithium methoxide, in high yields. β-Phenylamino amides gave five-membered cyclic ureas stereospecifically. Side products of aryl or benzyl bromination were minimized. This procedure offers an easy access to various protected amines or diamines, which represent important synthetic precursors.

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“…An irreversible specific inhibitor of N-SMase is manumycin A [39] whereas competitive inhibitors have been extracted from Abies nephrolepis, Acer tegmentosum, and Ginkgo biloba [40]. A SM methylene analog, synthesized by Hofmann rearrangement of the alpha-hydroxyethyl-betahydroxy amide 4 followed by the intramolecular oxazolidinone ring formation as the key steps, has been designed as a N-SMase inhibitor [41]. Also SM nitrogen analog 1 synthesized by continuous Hofmann and Crutius rearrangement as key steps in constructing the 3-hydroxy-1,2-diamine structure in the backbone of 1 has SMase inhibitor effect [42].…”

Section: Inhibitors Of Sphingomyelin Utilizationmentioning

confidence: 99%

Sphingolipid Metabolism Inhibitors and Cell Function

Albi¹,

Magni²

2008

TOEIJ

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It has been widely shown that ceramide, ceramide phosphate, sphingosine and sphingosine-1-phosphate are molecules involved in cell proliferation, differentiation and apoptosis. The regulation of the enzymes that control their metabolism has an important role for cellular fate. Many studies in the field have shed light on sphingolipid metabolism inhibition and on its role in cell processes such as gene expression, DNA duplication and RNA transcription. The aim of this review is to collect, in a systematic way, the recent advances in the field of sphingolipid metabolism inhibitors, with special emphasis on their effects on cell function.

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Stereocontrolled Synthesis of a Sphingomyelin Methylene Analogue as a Sphingomyelinase Inhibitor

Cited by 37 publications

References 18 publications

Sphingomyelinases: enzymology and membrane activity

Sphingomyelinases: enzymology and membrane activity

Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide

Sphingolipid Metabolism Inhibitors and Cell Function

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Stereocontrolled Synthesis of a Sphingomyelin Methylene Analogue as a Sphingomyelinase Inhibitor

Cited by 37 publications

References 18 publications

Sphingomyelinases: enzymology and membrane activity

Sphingomyelinases: enzymology and membrane activity

Hofmann Rearrangement of Carboxamides Mediated by N-Bromo­acetamide

Sphingolipid Metabolism Inhibitors and Cell Function

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Product

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Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide