Synthesis of an isosteric phosphonate analog of cytidine 5'-monophospho-3-deoxy-D-manno-2-octulosonic acid

Norbeck, Daniel W.; Kramer, James B.; Lartey, Paul A.

doi:10.1021/jo00387a011

Cited by 79 publications

(16 citation statements)

References 1 publication

(2 reference statements)

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“…Electron-rich aromatic compounds (e.g., 19) behave as C-nucleophiles only when faced with alkynyl ketoses (11,12), although the main reaction course observed was the formation of bis-arylated open-chain derivatives (26 and 30). The formation of bis-arylated compounds (Type D, Scheme 6) can be rationalized simply by considering that the intermediate C-ketoside (B) would be prone to undergo C1ϪO bond cleavage to form a propargyl-benzyl cation (e.g., C) that could react further with 12 to generate structures of type D. It is noteworthy, however, that the ketoses 13 and 14 fail to undergo similar reactions with 19, and we ascribe this behavior to steric and stereoelectronic factors, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…As successful nucleophilic partners, we have identified allyltrimethylsilane, trimethylsilyl cyanide, trimethylsilylazide, and one silyl enol ether. 1,3,5-Trimethoxybenzene behaves as a nucleophile and yielded an open-chain bis-arylated compound upon reaction with alkynyl ketoses (11,12), whereas the phenyl and methyl ketoses (13,14) failed to yield any coupled product. The reaction of ketoses with trimethylsilyl azide permits an efficient entry into the corresponding N-ketopyranosides.…”

Section: Resultsmentioning

confidence: 99%

“…[4] On the other hand, C-ketosides [5] or bis-C,C-glycosides [6] (2) have not found similar favor, [7] although methods for the preparation of spirocyclic bis-C,C-glycosides [6,8,9] and C-glycosides of ulosonic acids [10,11] have been reported by several groups.…”

Section: Introductionmentioning

confidence: 99%

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Stereoselective Synthesis of C‐ and N‐Ketosides by Lewis Acid‐Catalyzed C‐ and N‐Glycosidation of Alkynyl, Phenyl, and Methyl Ketoses

et al. 2003

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Stereoselective Synthesis of C‐ and N‐Ketosides by Lewis Acid‐Catalyzed C‐ and N‐Glycosidation of Alkynyl, Phenyl, and Methyl Ketoses

et al. 2003

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“…Several groups have pursued inhibition of KDO metabolism as a strategy for the development of novel anti-infective agents [279]. …”

Section: Figure 82 Bioactivation Of 6-mercaptopurinementioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

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“…This bisubstrate was tested as an inhibitor for chitin synthase (an important target for antifungal agents), but showed no activity. [134][135][136][137][138][139][140][141] . The same group also synthesized several multisubstrate adducts, but none had inhibitory effect.…”

Section: -14-galactosyltransferasementioning

confidence: 99%

Multisubstrate adduct inhibitors: Drug design and biological tools

Calvez

Scott²,

Migaud

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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Synthesis of an isosteric phosphonate analog of cytidine 5'-monophospho-3-deoxy-D-manno-2-octulosonic acid

Cited by 79 publications

References 1 publication

Stereoselective Synthesis of C‐ and N‐Ketosides by Lewis Acid‐Catalyzed C‐ and N‐Glycosidation of Alkynyl, Phenyl, and Methyl Ketoses

Stereoselective Synthesis of C‐ and N‐Ketosides by Lewis Acid‐Catalyzed C‐ and N‐Glycosidation of Alkynyl, Phenyl, and Methyl Ketoses

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Multisubstrate adduct inhibitors: Drug design and biological tools

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