A Simple Method for Synthesis of Spongosine, Azaspongosine, and Their Antiplatelet Effects

Ojha, L. M.; Gulati, D.; Seth, Neena; Bhakuni, D. S.; Pratap, Ramendra; Agarwal, Khushboo

doi:10.1080/15257779508010711

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…The nucleoside base was then coupled with protected ribose under Lewis acid conditions without prior base silylation to yield the 2′,3′,5′-tri-O-benzoyl 2-methylthioadenosine nucleoside in 48% yield. 31 Unfortunately, the nucleoside tri-O-benzoate was found to be unsuitable since we could not get complete removal of the benzoyl groups after threonine coupling without simultaneous t 6 A side-chain hydrolysis. Therefore, the benzoyl groups were removed from compound 2 with sodium methoxide in methanol and then the sugar hydroxyls reprotected as the acetates.…”

Section: Resultsmentioning

confidence: 99%

“…2-Methylthioadenine base 1 was synthesized in four steps starting from thiourea and malononitrile following literature procedures in 21% overall yield. , Compound 1 could also be made from commercially available 4,6-diamino-2-mercaptopyridine in three steps. The nucleoside base was then coupled with protected ribose under Lewis acid conditions without prior base silylation to yield the 2‘,3‘,5‘-tri- O -benzoyl 2-methylthioadenosine nucleoside in 48% yield . Unfortunately, the nucleoside tri- O -benzoate was found to be unsuitable since we could not get complete removal of the benzoyl groups after threonine coupling without simultaneous t 6 A side-chain hydrolysis.…”

Section: Resultsmentioning

confidence: 99%

“…1 H chemical shifts are reported relative to tetramethylsilane at 0.0 ppm and referenced to the residual proton signal of the deuterated solvents. 31 P chemical shifts are relative to external phosphoric acid at 0.0 ppm. Analytical thin-layer chromatography (TLC) was carried out on silica gel 60F-254 plates.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside

Bajji

Davis

2002

J. Org. Chem.

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The synthesis of a protected form of the hypermodified nucleoside, N-[(9-beta-D-ribofuranosyl-2-methylthiopurin-6-yl)carbamoyl]threonine, (ms2t6A) is reported. The hypermodified nucleoside was subsequently elaborated to the protected nucleoside phosphophoramidite using a protecting group strategy compatible with standard RNA oligonucleotide chemistry. The phosphoramidite reagent was then used to synthesize the 17-nucleotide RNA hairpin having the sequence of the anticodon stem-loop (ASL) domain of human tRNA(Lys,3), the primer for HIV-1 reverse transcriptase. Introduction of the modification at position 37 of the tRNA ASL modestly decreases the thermodynamic stability of the RNA hairpin as has been seen previously for the prokaryotic t6A nucleoside lacking the 2-methylthio substituent. 2D NOESY NMR spectra of the ms2t6A containing tRNA ASL indicate that the threonyl side chain adopts a conformation similar to that seen in the solution structure of the analogous t6A containing E. coli tRNA(Lys), despite the presence of the bulky methylthio group. This synthetic approach allows for site-specific incorporation of the hypermodified nucleoside and should facilitate future studies directed at understanding the roles of nucleoside modification in modulating the stability and specificity of biologically important RNA-RNA interactions. Our synthesis of the ms2t6A containing RNAs demonstrates that this methodology is suitable for obtaining quantities of RNA required for structural studies of the HIV primer tRNA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside

Bajji

Davis

2002

J. Org. Chem.

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“…[18,19] One such compound, 2-methoxyadenosine (1, Figure 1), commonly known as spongosine, [20,21] which was isolated from the Caribbean sponge Cryptotethia crypta, has been shown to have antiviral activity [22] and antiplatelet properties. [23] It is also used in the treatment of B-cell proliferative diseases [24] and in the treatment of pain. [25] Spongosine was not only the first methoxy purine to be found in nature, but also one of the first O-methyl compounds to be isolated from animal tissues.…”

Section: Introductionmentioning

confidence: 99%

A Convenient Route for the Synthesis of 3‐Deazaspongosine

Bande

Herdewijn

2013

Eur J Org Chem

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The first chemical synthesis of the 3‐deazaspongosine nucleoside is described, starting from commercially available 4‐amino‐2,6‐dichloropyridine. The key step is the introduction of required functional groups at the 2 and 6 positions of the 4‐amino‐3‐nitropyridine without any conflict in the synthesis of nucleobase. Regioselective nucleophilic substitution with allyl alkoxide at the 2 position of 4‐amino‐2,6‐dimethoxypyridine, followed by sequential deallylation and chlorination led to the desired 2‐chloro derivative. Ring closure of the 3,4‐diaminopyridine and stereoselective glycosylation of the imidazo[4,5‐c]pyridine with tetraacetate‐protected ribofuranose gave only the N9‐β‐isomer. A final nucleophilic displacement of the 6‐chloride by hydrazine followed by reduction with Raney Nickel gave the desired 3‐deazaspongosine.

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Synthesis Of Nucleosides

Vorbrüggen¹,

1999

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This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.

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A Simple Method for Synthesis of Spongosine, Azaspongosine, and Their Antiplatelet Effects

Cited by 8 publications

References 13 publications

Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside

Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside

A Convenient Route for the Synthesis of 3‐Deazaspongosine

Synthesis Of Nucleosides

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A Simple Method for Synthesis of Spongosine, Azaspongosine, and Their Antiplatelet Effects

Cited by 8 publications

References 13 publications

Synthesis of the tRNALys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms2t6A Nucleoside

Synthesis of the tRNALys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms2t6A Nucleoside

A Convenient Route for the Synthesis of 3‐Deazaspongosine

Synthesis Of Nucleosides

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Product

Resources

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Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside

Synthesis of the tRNA^Lys,3 Anticodon Stem-Loop Domain Containing the Hypermodified ms²t⁶A Nucleoside