Bicyclic guanidino ketones

Houghten, Richard A.; Simpson, R.; Hanson, Robert N.; Rapoport, Henry

doi:10.1021/jo00393a017

Cited by 17 publications

(8 citation statements)

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“…The absorbance of the guanidino-sugars was measured at 231 nm as a function of pH. The absorbance of cyclic guanidine compounds such as 2-iminoimidazolidine has been determined (pH 12.0, λ max = 213 nm, ε = 4250) . At low pH, the spectrum exhibited a minimum at 231 nm.…”

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confidence: 99%

Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

et al. 1996

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Cyclic guanidino-sugars with different pK a values are designed and synthesized as transition-state analog inhibitors of galactosidases. Characterization of these structures (7, 10, 12) reveals that 7 and 10 are in a pHdependent equilibrium between a furanose form and a mixture of neutral and protonated tetrahydropyrimidine forms. In contrast, the O-linked guanidino-sugar 12 exists as the tetrahydropyrimidine forms above pH 5. The furanosetetrahydropyrimidine equilibrium can thus be modulated with the appropriate N-substituent which affects the guanidinosugar pK a value. Enzymatic inhibition by 7, 10, and 12 is also pH-dependent, indicating that the enzymes recognize the tetrahydropyrimidine form. Evidence is presented to support a dominant role for the uncharged form of the six-membered cyclic guanidino-sugar in the inhibition of galactosidases. Though the inhibition potency is moderate (K i range 4-50 µM), the use of cyclic guanidino-sugars in the study provides new insights into the mechanism of inhibition of glycosidases.Oligosaccharide biosynthesis and degradation pathways are crucial to such diverse processes as HIV-1 replication, inflammation, blood clotting, cell differentiation, tumor development, cell routing, diabetes, and other metabolic disorders. Mechanistic understanding 1 and inhibition 2-5 of the enzymes that direct these reactions (glycosidases, glycosyltransferases) are areas of considerable interest. Both classes of enzymes are thought to proceed through a flattened half-chair (or twist-boat) conforma-X

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confidence: 99%

Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

et al. 1996

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“…The gauge-including atomic orbital (GIAO) NMR chemical shift calculation of C-2 for 3 using EDF2/6-31G*//EDF2/6-31G* indicated δ C 169.2 (Δ0.1) (Figure ). Rapoport et al reported a guanidino carbon signal at δ C 165.3 in a synthetic bicyclic [3.3.1] guanidine (Calcd δ C 165.5 (Δ0.2), Figure S7). The relative configurations of C-4a, C-6, and C-8a could be determined due to the fixed bridged structure of 3 .…”

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confidence: 74%

Identification of Tricyclic Guanidino Compounds from the Tetrodotoxin-Bearing Newt Taricha granulosa

2021

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The biosynthesis of the potent neurotoxin tetrodotoxin (TTX, 1) is still unresolved. We used MS-guided screening and nuclear magnetic resonance analyses including long-range HSQMBC to characterize two novel skeletal tricyclic guanidino compounds, Tgr-288 (2a and 2b) and Tgr-210 (3), from the TTX-bearing newt, Taricha granulosa. The presence of these compounds in toxic newts is congruent with a previously proposed pathway for TTX biosynthesis in terrestrial organisms that includes a monoterpene precursor and the production of structurally diversified guanidino compounds.

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“…Particularly, they have been featured in the synthesis of natural products such as DL-capreomycidine (eq 13), 14 and in Rappoport's bicyclic guanidines with a bridgehead nitrogen atom (eq 14). 15 All these studies were carried out using racemic diamines.…”

Section: Synthesis Of Guanidine Derivativesmentioning

confidence: 99%

N-[Bis(methylthio)methylene]-p-toluenesulfonamide

Liu

Hsung

2004

Encyclopedia of Reagents for Organic Synthesis

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Bicyclic guanidino ketones

Cited by 17 publications

References 2 publications

Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

Identification of Tricyclic Guanidino Compounds from the Tetrodotoxin-Bearing Newt Taricha granulosa

N-[Bis(methylthio)methylene]-p-toluenesulfonamide

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Bicyclic guanidino ketones

Cited by 17 publications

References 2 publications

Cyclic Guanidino-Sugars with Low pKa as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

Cyclic Guanidino-Sugars with Low pKa as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

Identification of Tricyclic Guanidino Compounds from the Tetrodotoxin-Bearing Newt Taricha granulosa

N-[Bis(methylthio)methylene]-p-toluenesulfonamide

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Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms

Cyclic Guanidino-Sugars with Low pK_a as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species Are the Active Forms