Acyclic Nucleotides Related to Clitocine: Synthesis and Anti-HIV Activity

Franchetti, Palmarisa; Cappellacci, Loredana; Sheikha, Ghassan Abu; Grifantini, Mario; Loi, A. G.; Montis, A. De; Mg, Spiga; Colla, Paolo La

doi:10.1080/15257779508012436

Cited by 9 publications

(4 citation statements)

References 1 publication

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“…UV (pH 12): Ama* 252 nm (e 5900), 278 (e 8900). (13). The title compound was prepared from 10 by the same procedure used for 1 in 88% yield, as a white solid.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

Franchetti¹,

Sheikha²,

Cappellacci³

et al. 1995

J. Med. Chem.

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(R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

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“…UV (pH 12): Ama* 252 nm (e 5900), 278 (e 8900). (13). The title compound was prepared from 10 by the same procedure used for 1 in 88% yield, as a white solid.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

Franchetti¹,

Sheikha²,

Cappellacci³

et al. 1995

J. Med. Chem.

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“…Entry 15 amine was prepared according to a literature procedure 24 and entry 16 amine was prepared according to a procedure described by Franchetti. 25 Analytical information 1 H and 13 C NMR spectra were recorded on a Bruker Avance instrument at 25 uC at 500 MHz and 125.8 MHz, respectively, using DMSO-d 6 as a solvent and using its signal as a reference. Chemical shifts (d) and coupling constants (J) were expressed in ppm and Hz, respectively.…”

Section: Experimental Details General Informationmentioning

confidence: 99%

One-pot build-up procedure for the synthesis of variously substituted purine derivatives

et al. 2012

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In this article, we report a one-pot build-up procedure leading to 6-chloro-or 2-amino-6chloropurines bearing various alkyl or aryl substituents in position N-9. This reaction is simple, fast and effective with up to 96% yields depending on the starting amine. This reaction may be easily combined with further nucleophilic displacement of the C-6 chlorine atom using various reagents, making this procedure very attractive in the field of medicinal chemistry pertaining to compounds based on a purine scaffold.

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“…Franchetti and his collaborators prepared new nucleotide analogues [17] The protection of cell cultures against HIV-1-and HIV-2-induced cytopathogenicity was observed with clitocine analogues 67 to 70, albeit with slightly lower selectivity and activity than PMEA and PMEDAP (Table 22.2). Analogous with the increased activity of PMEDAP compared to PMEA [18], 69 and 70 -the analogues of PMEDAP and (R)-PMPDAP, respectively -exhibited a four-fold higher activity against HIV-1 than 67 and 68 (analogues of PMEA and (R)-PMPA, respectively).…”

Section: Acyclic Analoguesmentioning

confidence: 99%

Clitocine and Its Analogues

Shin¹,

Min²

2008

Modified Nucleosides

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Guided by the insecticidal activity against the agricultural pest insect Pectinophora gossypiella, Kubo and Kim isolated clitocine (1a) [1], along with adenosine, from Clitocybe inversa, a medium-sized, buff-colored mushroom found in western North America. The NMR spectral data for clitocine was found to be very similar to that of adenosine, with the exception of the absence of the C-8 carbon peak of adenosine, while the low chemical shift of the 4-NH proton suggested strong hydrogen bonding between the 5-NO 2 and 4-NH groups. Later, Moss and coworkers [2] confirmed its structure through X-ray crystallographic analysis: as postulated earlier by Kubo et al., the entire aglycone moiety resembles a tricyclic ring system as a result of the hydrogen bonding between the 4-NH and 6-NH protons and the NO 2 group. SynthesisThe interesting biological activity of clitocine, together with its biogenetically close relationship to adenosine, triggered an immediate attempt to synthesize the molecule de novo. Two years after its initial isolation, two independent syntheses have now been completed. The first synthesis [3] is based upon the condensation of 2,3,5-tribenzoylribofuranosylamine (2) with 4,6-dichloro-5-nitropyrimidine (3) in the presence of a base to give a mixture of the a-and b-anomers in a 7 : 1 ratio (Scheme 22.1), although the yield (19%) is relatively poor. Deprotection of the benzoate group of 4 using a methanolic ammonia solution produced clitocine with a 71% yield. In order to improve the efficiency and reproducibility of the coupling reaction, an acetonideprotected amino sugar (5) was employed for the coupling reaction with 4-chloro-5-Modified Nucleosides: in Biochemistry, Biotechnology and Medicine. Edited by Piet Herdewijn

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Acyclic Nucleotides Related to Clitocine: Synthesis and Anti-HIV Activity

Cited by 9 publications

References 1 publication

Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

One-pot build-up procedure for the synthesis of variously substituted purine derivatives

Clitocine and Its Analogues

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