Synthesis of Pyranoid Analogues of the Anti‐HIV Active 3′‐Deoxy‐2′,3′‐didehydrothymidine (D4T)

Hansen, H. B.; Pedersen, Erik B.; Vestergaard, Bent Faber

doi:10.1002/ardp.19923250808

Cited by 8 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EIMS; m/e 406 (M+). 400-MHz SH NMR (DMSO-dg): 8 2.42 (s, 3H, CH3), 3.35- 3.42 (m, 2H, H-4', H-5'), 3.49 (t, <7=11 Hz, 1H, H-l'a), 3.61 (m, 1H, H-6'), 3.67 (m, 1H, H-3'), 3.87 (dd, J = 5.5 and 11 Hz, 1H, H-l'd), 4.14-4.25 (m, 2H, H-2, H-6"), 5.05 (s, 1H, PhCH), 5. 1.5-Anhydro-4,6-O-benzylidene-2-O-p-toluoyl-D-glucitol (9). A mixture of the sugar derivative 7 (8.5 g, 33.67 mmol) and dibutyltin oxide (8.38 g, 33.67 mmol) in 250 mL of benzene was refluxed for 16 h with azeotropic removal of water.…”

Section: Methodsmentioning

confidence: 99%

“…The acetyl groups were removed with sodium methoxide. A benzylidene protecting moiety was introduced by reaction with benzaldehyde in the presence of zinc chloride,13 thus affording l,5-anhydro-4,6-0-benzylidene-D-glucitol, 7. Selective reaction of the hydroxyl function at position 2 was feasible following activation with dibutyltin oxide.14 Position 2 either was selectively protected as an ester with toluoyl chloride or was functionalized with a leaving group by tosyl chloride, affording 1,5-anhydro-4,6-0-benzylidene-2-O-p-toluoyl-D-glucitol (9) or l,5-anhydro-4,6-0-benzylidene-2-0-p-(tolylsulfonyl)-D-glucitol (8) in yields of 78% and 82%, respectively. The hydroxyl group in position 3 of 8 and 9 was removed by conversion to the 2,4-dichlorophenylthiocarbonate derivatives with thiophosgene, 4-(dimethylamino)pyridine (DMAP), and 2,4dichlorophenol, followed by a Barton-type reduction (BusSnH, AIBN) yielding 10 and 11 in 64 % and 75 % yield, respectively.18 These reactions gave lower yields when smaller amounts of DMAP were used because of the hydrolysis of the benzylidene moiety as a side reaction.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Verheggen

Toppet²,

Snoeck³

et al. 1993

J. Med. Chem.

151

102

View full text Add to dashboard Cite

The synthesis of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol 4b at a concentration of 0.07 microgram/mL. This activity must be dependent on a specific phosphorylation by the virus-encoded thymidine kinase (TK), since compound 4b was inactive against TK-deficient mutants of HSV-1. The corresponding cytosine 4c and guanine 4e analogues showed activity against HSV-1, HSV-2, and other herpes viruses (i.e. cytomegalovirus, varicella-zoster virus) at concentrations well below the cytotoxicity threshold (2 and 20 micrograms/mL, respectively). At these concentrations, compounds 4c and 4e proved also inhibitory to the growth of human T-cells (i.e. MT-4, CEM, MOLT-4).

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Verheggen

Toppet²,

Snoeck³

et al. 1993

J. Med. Chem.

151

102

View full text Add to dashboard Cite

show abstract

“…Hex-2-enopyranosyl and hex-3-enopyranosyl nucleoside analogues, 73-75 (Fig. 36), which were synthesized by Hansen et al [94] and by Herdewijn et al [95,96], were devoid of antiviral activity and cytotoxicity against HSV-1 or HIV-1. Pérez-Pérez et al [97,98] reported the synthesis of a pentopyranosyl analogue of d4T monophosphate (compound 76), as well as the isonucleoside of guanine 77 and its enantiomer 78 (Fig.…”

Section: Hexopyranose Unsaturated Nucleosi-desmentioning

confidence: 99%

Σύνθεση Μιας Νέας Τάξης Φθορο - Θειο - Νουκλεοζιτών Με Πιθανή Αντιϊκή Και Αντικαρκινική Δράση

Τσουκαλά¹

View full text Add to dashboard Cite

Synthesis Of Nucleosides

Vorbrüggen¹,

1999

View full text Add to dashboard Cite

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.

show abstract

Synthesis of Pyranoid Analogues of the Anti‐HIV Active 3′‐Deoxy‐2′,3′‐didehydrothymidine (D4T)

Cited by 8 publications

References 18 publications

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

Σύνθεση Μιας Νέας Τάξης Φθορο - Θειο - Νουκλεοζιτών Με Πιθανή Αντιϊκή Και Αντικαρκινική Δράση

Synthesis Of Nucleosides

Contact Info

Product

Resources

About