122567-97-9Relevant articles and documents
Highly efficient synthesis of 2′,3′-didehydro-2′, 3′-dideoxy-β-nucleosides through a sulfur-mediated reductive 2′,3′-trans-elimination. From iodomethylcyclopropanes to thiirane analogs
De Cienfuegos, Luis álvarez,Mota, Antonio J.,Rodríguez, Concepción,Robles, Rafael
, p. 469 - 473 (2005)
A very simple methodology to achieve 2′,3′-didehydro-2′, 3′-dideoxy nucleoside derivatives was performed by means of the treatment of 2′-deoxy-2′-iodo-β-nucleosides with NaHS. The same procedure leads to thiiranes from iodomethylcyclopropane derivatives. Taking into account the thiophilic properties of iodine, a very simple methodology to achieve 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides in high yield was performed, using mild, and inexpensive conditions, by means of the treatment of 2′-deoxy-3′,5′-dibenzoyl-2′-iodo-β- nucleoside derivatives with NaHS. The process has shown to be highly dependent of the relative geometry between the iodine atom and the adjacent leaving group. In this way, different essays carried out with pyranose derivatives have concluded in no reaction when the vicinal groups to eliminate do not adopt a trans-diaxial disposition. In addition, the treatment of 2-iodomethyl- cyclopropane-1,1-dicarboxylic acid diethyl ester under the same conditions softly and readily leads to the obtention of a mixture of the expected 2-allyl-malonic acid diethyl ester (as the minor product) and the thiirane derivative 2-thiiranylmethyl-malonic acid diethyl ester (as the major product). In this case, the responsible of the reaction progress are the nucleophilic properties of the sulfur atom rather than the thiophilic character of the iodine atom.
5'-Benzoyl-2'α'-bromo-3'-O-methanesulfonylthymidine: A Superior Nucleoside for the Synthesis of the Anti-Aids Drug D4T (Stavudine).
Chen, Bang-Chi,Quinlan, Sandra L.,Stark, Derron R.,Reid, J. Gregory,Audia, Vicki H.,et al.
, p. 7957 - 7960 (1995)
The anti-AIDS drug d4T is prepared in 75percent overall yiled starting from the readily available ribonucleoside 5-methyluridine (1).The key step in this new synthesis is the zinc-induced reductive elimination of the bromomesylate 4, which affords d4T without nucleoside bond cleavage.A facile procedure for the deprotection/isolation of this highly water soluble product is also described.
A new thymine free synthesis of the anti-AIDS drug d4T via regio/stereo controlled β-elimination of bromoacetates
Chen, Bang-Chi,Quinlan, Sandra L.,Reid, J. Gregory,Spector, Richard H.
, p. 729 - 732 (1998)
The anti-AIDS drug d4T was prepared without contamination of the nucleoside bond cleaved by-product thymine from the readily available ribonucleoside 5-methyluridine (1). This was accomplished by using a new strategy which involved a regio/stereo controlled β-elimination of trans-bromoacetates 6.
Independent synthesis and fate studies of impurities in process intermediates of the anti-AIDS drug d4T
Reddy, Jayachandra P.
, p. 203 - 207 (1998)
Impurities in isolated intermediates in a process to prepare d4T were identified, independently synthesized, and then taken through the process to determine their ultimate fate. Some of the products from these fate studies were also independently synthesized and used in the validation of impurity assay methods.
Multistep Continuous Flow Synthesis of Stavudine
Sagandira, Cloudius R.,Akwi, Faith M.,Sagandira, Mellisa B.,Watts, Paul
, p. 13934 - 13942 (2021/06/28)
Herein, we demonstrate an elegant multistep continuous flow synthesis for stavudine (d4T), a potent nucleoside chemotherapeutic agent for human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions. This was accomplished via six chemical transformations in five sequential continuous flow reactors from an affordable starting material, 5-methyluridine. In the first instance, single step continuous flow synthesis was demonstrated with an average of 97% yield, 21.4 g/h throughput per step, and a total of 15.5 min residence time. Finally, multistep continuous flow synthesis of d4T in 87% total yield with a total residence time of 19.9 min and 117 mg/h throughput without intermediate purification was demonstrated.
Methyl ketone derivative, and preparation method and applications thereof
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Page/Page column 0043, (2017/08/28)
The invention discloses a methyl ketone derivative, and a preparation method and applications thereof. The preparation method comprises following steps: a ketone derivative and an organic peroxide are dissolved in a solvent, and reaction is carried out at 80 to 130 DEG C so as to obtain methyl pyrimidone and a methyl pyrimidone derivative. According to the preparation method, the ketone derivative is taken as a starting material; the raw materials are easily and widely available; products of different kinds can be obtained via the preparation method, and can be used directly or used in other further reaction. No metal is involved, so that the preparation method is suitable to be applied in pharmaceutical preparation technology. The preparation method is short in route, mild in reaction conditions, simple in reaction operation and postprocessing process, and high in yield, and is suitable for large-scale production.
Simple entry to 3'-substituted analogues of anti-HIV agent stavudine based on an anionic O --> C stannyl migration.
Kumamoto, Hiroki,Tanaka, Hiromichi
, p. 3541 - 3547 (2007/10/03)
Reaction of 5'-O-protected derivatives of the anti-HIV agent stavudine (d4T) with LTMP was investigated with the aim to lithiate the vinylic hydrogens (H-3' and H-2'). When the lithiation of the 5'-O-tert-butyldiphenylsilyl derivative 5 was carried out in the presence of HMPA, an anionic silyl migration took place to give the 3'-C-silylated product 4a. The stannyl version of this reaction was found to be also possible, which has disclosed a highly simple entry to the d4T analogues variously substituted at the 3'-position by manipulating the 3'-C-stannyl d4T as a common intermediate.
Free radical chemistry of nucleosides and nucleotides. Ring opening of C4'-radicals
Crich, David,Yao, Qingwei
, p. 305 - 318 (2007/10/03)
It is demonstrated that nucleotide C4' radicals may be generated from a C4'-thiolester on treatment with tributyltin hydride. When the reaction is conducted in benzene at reflux the C4' radical expels the C3'-phosphate group to give a radical cation. This species undergoes deprotonation to an allylic radical which suffers cleavage of the deoxyribose ring. Similar reactions are observed when the reaction is conducted with tris(trimethylsilyl)silane in place of the stannane. In methanolic benzene the radical cation is trapped by methanol to give a new C4' radical which is quenched before ring opening. The behavior of C4' radicals toward ring opening is discussed in terms of the conformations imposed by the substituents at C3'.
Transformations of β-D-Xylofuranosyl Nucleosides. Synthesis of 3′-Deoxy-2′,3′-didehydrothymidine (D4T)
Mustafin,Gataullin,Spirikhin,Abdrakhmanov,Tolstikov
, p. 1784 - 1790 (2007/10/03)
3′-Deoxy-2′,3′-didehydrothymidine was synthesized through a 10-step procedure starting from D-xylose. The overall yield of the target product was 28%.
