Nucleosides of thioguanine and other 2-amino-6-substituted purines from 2-acetamido-5-chloropurine

Efficient synthetic route to novel 2'-spirocyclopropanoid 4'-deoxythreosyl phosphonic acid nucleosides was described from 1,4-dihydroxy-2-butene. Cyclopropane moiety was prepared via ester enolate alkylation using (2-chloroethyl)dimethylsulfonium iodide. Synthesized nucleoside analogues 16, 19, 23 and 26 were tested for anti-HIV activity as well as cytotoxicity. However, none of them showed any anti-HIV activity or cytotoxicity up to 100 µM.

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel 2'-Spirocyclopropanoid 4'-Deoxythreosyl Phosphonic Acid Nucleoside Analogues

Shen¹,

Hong

2013

“…The 2-amino-6-chloropurine derivative 22b was treated with TMSBr to provide phosphonic acid and sequentially treated with sodium methoxide and 2-mercaptoethanol in methanol to give the desired guanine phosphonic acid 23 (Scheme 4). 20 Furthermore, the guanine phosphonic acid analogue 26 was synthesized from 21 via transfer catalytic hydrogenation, ammonolysis, and hydrolysis using conditions similar to those described for the synthesis of the adenine 6, line derivative 16. To synthesize the thioester-protected analogue, compound 16 was reacted with thioester 27 21 in the presence of 1-(2-mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole (MSNT) 22 to provide the bis(SATE) derivative as a target compound 28 (Scheme 5).…”

Section: Resultsmentioning

confidence: 99%

“…Desilylation of 17b was performed using a procedure similar to that described for 8: yield 78%; UV (MeOH) λ max 269.5 nm; (rel)-(1'R,2'R,3'S)-9-(3'-Carbaldehyde-2'-fluoro-tetrahydrofuran-1'-yl) 2-fluoro-6-chloropurine (19). Oxidation of 18 was performed using the Dess-Martin reaction conditions described for 9: yield 66%; (rel)-(1'R,2'R,3'S)-9-(3'-Vinyl-2'-fluoro-tetrahydrofuran-1'-yl) 2-fluoro-6-chloropurine} phosphonate (20). Wittig olefination of the aldehyde 10 was performed using a procedure similar to that described for 10: yield 59%; (rel)-(1'R,2'R,3'S)-Diethyl {9-(3'-vinyl-2'-fluoro-tetrahydrofuran-1'-yl) 2-fluoro-6-chloropurine} phosphonate (21).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Novel 2'-Fluoro-5'-deoxyphosphonic Acids and Bis(SATE) Adenine Analogue as Potent Antiviral Agents

Shen¹,

Hong

2013

Novel 5'-deoxythreosyl purine phosphonic acid analogues containing a 2'-electropositive moiety such as fluorine atom, were designed and synthesized from commercially available 1,3-dihydroxy acetone. Condensation successfully proceeded from a glycosyl donor 6 under Vorbrüggen conditions and cross-metathesis gave the desired phosphonate analogues 7a, 7b, 17a and 17b. The synthesized nucleoside phosphonic acid analogues 13, 16, 23, 26, 28 were subjected to antiviral screening against HIV-1. The bis(SATE) adenine analogue 28 exhibited significant in vitro activities against HIV-1.

“…The 2-amino-6-chloropurine derivative 19b was treated with TMSBr to provide phosphonic acid, and then treated with sodium methoxide and 2-mercaptoethanol in methanol to give the desired guanine vinylidene phosphonic acid 20 (Scheme 2). 19 The guanine phosphonate 23 was synthesized from 18 by transfer catalytic hydrogenation and by ammonolysis and hydrolysis using conditions similar to those described for the synthesis of 20.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Conformation of Novel 3'-Branched Threosyl-5'-Deoxyphosphonic Acid Nucleoside Analogues

Shen¹,

Kang²,

Kim³

et al. 2012

The discovery that threosyl phosphonate nucleoside (PMDTA, EC 50 = 2.53 µM) is a potent anti-HIV agent has led to the synthesis and biological evaluation of 5'-deoxy versions of threosyl phosphonate nucleosides. In the present study, (E)-3'-phosphonoalkenyl and 3'-phosphonoalkyl nucleoside analogues 13, 16, 20 and 23 were synthesized from acetol and tested for anti-HIV activity and cytotoxicity. The adenine analogue 16 was found to exhibit moderate in vitro anti-HIV-1 activity (EC 50 = 22.2 µM).