114987-18-7

Usage

InChI:InChI=1/C9H9N5O/c10-8-7-9(12-5-11-8)14(6-13-7)3-1-2-4-15/h2-3,5-6,15H,4H2,(H2,10,11,12)

Upstream product

• 114978-79-9 4-(6-Amino-purin-9-yl)-but-2-yn-1-ol 
• 144041-65-6 (S)-(+)-N⁹-(4-acetoxy-1,2-butadien-1-yl)hypoxanthine 
• 66224-66-6 adenine 
• 114987-15-4 N⁹-(4-Chloro-2-butyn-1-yl)adenine 
• 144019-51-2 (S)-(+)-N⁹-(4-acetoxy-1,2-butadien-1-yl)adenine 

Downstream Products

• 117011-71-9 N⁹-(4-chlorobuta-1,2-dien-1-yl)adenine 
• 114987-18-7 (-)-Adenallene 
• 117011-49-1 (+)-Hypoxallene 
• 715-68-4 9-(4-hydroxybutyl)adenine 
• 30955-07-8 6-amino-9-(4-methylphenylsulfonyl)-9H-purine 

Relevant academic research and scientific papers

(R)-(-)- and (S)-(+)-Adenallene: Synthesis, Absolute Configuration, Enantioselectivity of Antiretroviral Effect, and Enzymic Deamination

Synthesis of optically pure (-)- and (+)-adenallene 2 and 3 is described.Racemic adenallene (1a) was subjected to deamination with adenosine deaminase monitored by HPLC using a Chiralcel CA-1 column to give (-)-adenallene (2) and (+)-hypoxallene (4).The latter compound was converted to acetate 5.The reaction of 5 with trifluoromethanesulfonic anhydride and pyridine followed by ammonolysis furnished acetate 6 or (+)-adenallene (3) depending on the solvent used in the last step.Acetate 5 was smoothly transformed to the 6-chloro derivative 7, but an attempted ammonolysis led only to racemization and decomposition.Single crystal X-ray diffraction established the R-configuration of (-)-enantiomer 2.The latter forms a pseudosymmetric dimer in the lattice with the adenine moiety in an anti-like conformation.The torsional angles of the allenic bonds show departures from 90 deg (91 and 97 deg, respectively) and rotameric preference of the hydroxymethyl groups is different in both molecules of the dimer.The R-enantiomer 2 inhibited the replication and cytopathic effect of human immunodeficiency virus (HIV-1) in ATH8 cell culture with an IC50 of 5.8 μM, whereas the S-enantiomer 3 was less active (IC50>200 μM).The enantioselectivity of the anti-HIV effect is significantly lower than that of 2',3'-dideoxyadenosine.Kinetics of deamination of R- and S-enantiomers 2 and 3 catalyzed by adenosine deaminase gave the following parameters: Km values of R-form 3 and S-form 2 were 0.41 and 0.52 mM with Vmax being 530 and 18.5 μmol/min, respectively.Again, a much lower level of enantioselectivity of deamination was observed than that of D- and L-adenosine.These results indicate (i) different enantioselectivity of enantiomers 2 and 3 as HIV inhibitors and adenosine deaminase substrates and (ii) both R- and S-enantiomers 2 and 3 can function as nucleoside analogues with varied enantioselectivity for different enzymes or receptors.

Nucleic Acid Derived Allenols: Unusual Analogues of Nucleosides with Antiretroviral Activity

Racemic 1,2-butadien-4-ols substituted with a nucleic acid base were prepared by a base-catalyzed isomerization of the corresponding 2-butynols.With basic heterocycles such as adenine, cytosine, 5-methylcytosine, or N-guanine, the respective allenes were obtained without difficulty, but with guanine, side reactions were observed.Reaction of 2-butynols in stronger base (1 M NaOH) gave cyclized products-oxacyclopentenes 8a-c. (+/-)-Adenallene (3a) and (+/-)-cytallene (3c) are strong inhibitors of replication of human immunodeficiency virus(HIV) in vitro. (+/-)-Adenallene (3a) and butyne 6a are substrates for adenosine deaminase.Racemic 3a was deaminated quantitatively to (+/-)-hypoxallene (3h), indicating a low stereoselectivity as contrasted with the natural substrate-adenosine.When the deamination was stopped ad ca. 50percent conversion, (-)-adenallene (3a) and (+)-hypoxallene (3h) were obtained.Antiretroviral and adenosine deaminase substrate activities are discussed in terms of the similarity of several steric and stereoelectronic features of allenic derivatives of nucleic bases with those of the corresponding nucleosides or 2',3'-dideoxyribonuclesides.