Carbocyclic Ribosylamines:  Synthesis of 5-Substituted Carbocyclic β-Ribofuranosylamines

Slama, James T.; Mehta, Nimish; Skrzypczak‐Jankun, Ewa

doi:10.1021/jo060920l

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…The resolution of the (±)-γ-lactam 4 was carried out with savinase in 50% THF–phosphate buffer solution (pH 8.0) for 2 days, selectively producing only the optically pure γ-lactam (−)- 4 in 84% yield with an enantiomeric excess (ee) of more than 99%. It has been reported that the stereochemistry of OsO 4 -catalyzed hydroxylation of (−)-2-azabicyclo[2.2.1]hept-5-en-3-one (γ-lactam 3 ) can be controlled through the N–H protecting group of the lactam. , A large group sterically directs the hydroxylation to the exo face of an olefin, yielding a hydroxylation product that can be converted into an analogue of carbocyclic riboside, as the exo isomer was desired for our synthesis. Thus, a bulkier Boc protecting group would prevent the OsO 4 oxidation from the β-face of the olefin and favor the production of the α-diol.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam

et al. 2014

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2'-Fluoro-6'-methylene carbocyclic adenosine (FMCA) is a potent and selective inhibitor of wild type as well as drug-resistant hepatitis B virus (HBV) mutants. FMCA demonstrated excellent anti-HBV activity against both adefovir-resistant and lamivudine-resistant double (rtL180M/rtM204V) mutants as well as in lamivudine/entecavir triple mutants (L180M+S202G+M204V) in vitro. Its monophosphate prodrug (FMCAP) demonstrated a greater than 12-fold increase of anti-HBV activity in comparison to that of the nucleoside without elevation of cellular toxicity. In the preliminary in vivo study in chimeric mice harboring the lamivudine/entecavir triple mutant, FMCAP effectively reduced HBV viral load, while entecavir was not effective. Therefore, it was of great interest to develop an efficient synthetic procedure to support the preclinical investigation. In this article, a new approach for the synthesis of FMCA from a readily available starting material (Vince lactam) in 16 steps is described. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, D-2'-fluoro-6'-methylene cyclopentanol 14, has been developed from diazotization, elimination, stereoselective epoxidation, fluorination, and oxidation-reduction sequence of the Vince lactam in 14 steps. The utility of D-2'-fluoro-6'-methylene cyclopentanol 14 is demonstrated in the preparation of FMCA using the Mitsunobu coupling to introduce the adenine base to synthesize the final nucleoside.

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Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam

et al. 2014

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“…Slama et al studied the effects of steric bulk at the nitrogen of the Vince lactam in the hydroxylation reaction. The goals of the study included preparation of carbocyclic β-ribofuranosylamines . Since presence of bulky groups on the nitrogen exerts a profound effect in formation of exo-hydroxylation products, the authors considered studying the stereochemical effect of the approach of hydroxylating agent from the least hindered side of N-protected Vince lactam.…”

Section: Reactivity Profile Of Vince Lactammentioning

confidence: 99%

“…The goals of the study included preparation of carbocyclic β-ribofuranosylamines. 214 Since presence of bulky groups on the nitrogen exerts a profound effect in formation of exo-hydroxylation products, the authors considered studying the stereochemical effect of the approach of hydroxylating agent from the least hindered side of Nprotected Vince lactam. OsO 4 catalyzed cis-hydroxylation validated the hypothesis.…”

Section: Hydroxylation Of Vince Lactammentioning

confidence: 99%

2-Azabicyclo[2.2.1]hept-5-en-3-one: Chemical Profile of a Versatile Synthetic Building Block and its Impact on the Development of Therapeutics

2012

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| Chem. Rev. 2012, 112, 4642−4686 4.4.3. Enantioselective Synthesis of Various Heterocyclic Compounds via ROM-RCM Domino Metathesis of Ring-Opened Vince Lactam Derivatives 4669 4.5. Use of Vince Lactam as a Standard in Chemical Analysis of Compounds and Optical Activity of Stereoisomers 4669 5. Conclusions 4669 Author Information 4669 Corresponding Author 4669 Notes 4669 Biographies 4670 Acknowledgments 4670 Abbreviations 4670 References 4671V). The well-known preference of the hydrolase enzymes to attack a substrate from si face rather than re face was studied in the system via molecular modeling of the two tetrahedral intermediates. These studies revealed that the complexes modeled on re face for both the isomers of the racemate were highly unfavorable. Furthermore, the unpropitious steric Scheme 12. Biocatalytic Resolution of Vince Lactam Followed by Various Chemical Transformations to Obtain the Desired Stereoisomers of Synthetic Intermediates Scheme 13. Proposed Mechanistic Pathway for the Biocatalytic Hydrolysis of Vince Lactam Chemical Reviews Review dx.

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Total Synthesis of the Antiviral Natural Product Houttuynoid B

Kerl

Berger

Schmalz

2016

Chemistry A European J

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The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker-Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5-endo-dig cyclization and converted into a stable 1-hydroxybenzotriazole-derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.

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Carbocyclic Ribosylamines: Synthesis of 5-Substituted Carbocyclic β-Ribofuranosylamines

Cited by 6 publications

References 26 publications

Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam

Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam

2-Azabicyclo[2.2.1]hept-5-en-3-one: Chemical Profile of a Versatile Synthetic Building Block and its Impact on the Development of Therapeutics

Total Synthesis of the Antiviral Natural Product Houttuynoid B

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