The Synthesis of Some 5'-Thiopentofuranosylpyrimidines<sup>1</sup>

Reist, Elmer J.; Benitez, Allen; Goodman, Leon

doi:10.1021/jo01026a008

Cited by 82 publications

(40 citation statements)

References 4 publications

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“…Treatment of 1a with TsCl gave the p-toluenesulfonate 2 (in 68% yield [7]), which was converted in acceptable yield (58%) with potassium thioacetate in acetone to compound 3 [8]. Using basic medium (NaOH, NaOMe, NH 3 in MeOH) for the 5'-deprotection of 3, we isolated the symmetric disulfide that was formed in high yield.…”

mentioning

confidence: 99%

“…Using basic medium (NaOH, NaOMe, NH 3 in MeOH) for the 5'-deprotection of 3, we isolated the symmetric disulfide that was formed in high yield. But when we used an acidic medium for deprotection (HCl in MeOH), the free 5'-thiol was liberated [7], which reacted with 4,4'-dimethoxytrityl chloride ((MeO) 2 Tr-Cl) in H 2 O and AcOH to give compound 4 in 68% yield, after purification by flash chromatography [9]. The transformation of the 5'-S-acetyl-5'-thiothymidine 3 to the 5'-S-(4,4'-dimethoxytrityl)-5'-thiothymidine (4) was achieved under conditions usually applied for standard deprotection of the 5'-O-(4,4'-dimethoxytrityl) group.…”

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confidence: 99%

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Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Jahn‐Hofmann

Engels

2004

Helvetica Chimica Acta

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The incorporation of a specific cleavage site into an oligodeoxynucleotide can be achieved by utilizing the four 5′‐S‐(4,4′‐dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside 3′‐(2‐cyanoethyl diisopropylphosphoramidites) 5 and 15a–c (Fig. 1). Based on the silver ion assisted cleavage of PS and CS bonds, we synthesized oligodeoxynucleotides with an achiral 5′‐phosphorothioate linkage 3′–O–P–S–5′ by the solid‐phase phosphoramidite procedure. The efficient cleavage of these modified oligodeoxynucleotides can be detected by HPLC, PAGE, and surface plasmon resonance (SPR) spectrometry. The liberated 5′‐thiol moiety can be used directly for post‐reaction labeling with appropriately functionalized reporter groups.

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confidence: 99%

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confidence: 99%

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Jahn‐Hofmann

Engels

2004

Helvetica Chimica Acta

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“…Collected the white precipitate, and washed with cold ethyl ether, yielding 66 mg (0.254 mmol, 85%) compound 6. Compound 6 was soon kept in a case with nitrogen atomosphere at -20 • C. 1 …”

Section: Ss -3 5 -Dithio-2 -Deoxyuridinementioning

confidence: 99%

“…[1] But the work of both 3 ,5 hydroxyl groups were replaced by thiol was rarely mentioned before, not only because of the hard conformation conversion of 3 -position on the sugar ring, but also the easily formation of S-S linkage between bare thiol groups. In 1996, Reese's group developed an efficient route to synthesize the 3 ,5 -dithio-2 -deoxythymidine through 2,3 -anhydrothymidine.…”

Section: Introductionmentioning

confidence: 99%

Study on Disulfur-Backboned Nucleic Acids: Part 3. Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyuridine and Deoxycytidine

Shang

Wang

Cheng

et al. 2008

Nucleosides, Nucleotides and Nucleic Acids

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A general method is described for synthesizing 3',5'-dithio-2'-deoxypyrimidine nucleosides 6 and 13 from normal 2'-deoxynucleosides. 2,3'-Anhydronucleosides 2 and 9 are applied as intermediates in the process to reverse the conformation of 3'-position on sugar rings. The intramolecular rings of 2,3'-anhydrothymidine and uridine are opened by thioacetic acid directly to produce 3'-S-acetyl-3'-thio-2'-deoxynucleosides 3 or 5. To cytidine, OH(-) ion exchange resin was used to open the ring and 2'-deoxycytidine 10 was obtained in which 3'-OH group is in threo-conformation. The 3'-OH is activated by MsCl, and then substituted by potassium thioacetate to form the S,S'-diacetyl-3',5'-dithio-2'-deoxycytidine 12. The acetyl groups in 3',5' position are removed rapidly by EtSNa in EtSH solution to afford the target molecules 6 and 13. The differences of synthetic routes between uridine and cytidine are also discusssed.

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“…Since the 6-position of 1-substituted 5-fluorouracils is quite susceptible toward nuc leophilic attack (15)(16)(17), we suspected that FdUMP might exert its inhibitory effect by reaction with the proposed nucleophilic catalyst of thymidylate synthetase. Studies from this (18,19) and other (20,21 ) laboratories have since demonstrated this to be the case.…”

Section: -Fluoro-2' -Deoxyuridylate (Fdump)mentioning

confidence: 99%

Thymidylate Synthetase: Interaction with 5-Fluoro and 5-Trifluoromethyl-2′-Deoxyuridylic Acid

Santi

Pogolotti

James

et al. 1976

ACS Symposium Series

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Thymidylate synthetase catalyzes the reductive methylation of 2'-deoxyuridylate (dUMP) to thymidylate (TMP) with the concomitant conversion of 5, 10-methylene tetrahydrofolate (CH 2 FAH 4 ) to 7, 8-dihydrofolate (FAH 2 ) as depicted in Fi gure 1 (for a recent review, see reference 1). In this process the hydrogen at C-6 of FAH 4 is directly transferred to the methyl group of TMP (2).One of our objectives over the past few years has been to establish the mechanism of catalysis of thymidylate synthetase. Extensive investigations of chemical counterparts (3-6) have in dicated that the reaction is initiated by attack of a nucleophile at the 6-position of dUMP and that many, if not all, reactions along the pathway are facilitated by analogous nucleophilic catalysis.The proposed mechanism of this enzyme, as derived from investigations of chemical models is illustrated in Figure 2. It is proposed that the reaction is initiated by attack of a nucleophilic group of the enzyme to the 6-position of dUMP. In this manner, the 5-position of dUMP could be made sufficient ly nucleophilic (viz I, Figure 2) to react with CH 2 FAH 4 or an equivalent reactive species of formaldehyde. Thus, the initial condensation product between dUMP and CH 2 FAH 4 is now generally accepted (1, 7) to be one which is covalently bound to the enzyme and saturated across the 5, 6-double bond of dUMP (II). Proton abstraction from II would give the intermediate enolate III. As with the chemical models, III should readily undergo a β-elimination to produce the highly reactive exocyclic methylene intermediate IV and FAH 4 , bound to the enzyme in close proximity. Intermolecular hydride transfer from FAH 4 to IV would yield dTMP, FAH 2 , and the native enzyme. It should be emphasized that all of the aforementioned reactions and inter mediates have direct chemical counterparts, and are in complete accord with all available biochemical data.With the availability of a stable enzyme from an amethop terin resistant strain of Lactobacillus casei (8, 9) and facile methods for its purification (9-11), we undertook studies which 57 Downloaded by GEORGETOWN UNIV on August 25, 2015 |

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The Synthesis of Some 5'-Thiopentofuranosylpyrimidines¹

Cited by 82 publications

References 4 publications

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Study on Disulfur-Backboned Nucleic Acids: Part 3. Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyuridine and Deoxycytidine

Thymidylate Synthetase: Interaction with 5-Fluoro and 5-Trifluoromethyl-2′-Deoxyuridylic Acid

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The Synthesis of Some 5'-Thiopentofuranosylpyrimidines1

Cited by 82 publications

References 4 publications

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

Study on Disulfur-Backboned Nucleic Acids: Part 3. Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyuridine and Deoxycytidine

Thymidylate Synthetase: Interaction with 5-Fluoro and 5-Trifluoromethyl-2′-Deoxyuridylic Acid

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The Synthesis of Some 5'-Thiopentofuranosylpyrimidines¹