114987-19-8Relevant articles and documents
Synthesis, Absolute Configuration, and Enantioselectivity of Antiretroviral Effect of (R)-(-)- and (S)-(+)-Cytallene. Lipase-Catalyzed Enantioselective Acylations of (+/-)-N4-Acylcytallenes
Jones, Bryan C. N. M.,Silverton, James V.,Simons, Claire,Megati, Sreenivasulu,Nishimura, Hisao,et al.
, p. 1397 - 1405 (2007/10/02)
Enantioselectivity of acylations of (+/-)-cytallene (1b), (+/-)-N4-acetylcytallene (11a), (+/-)-N4-benzoylcytallene (11b), and (+/-)-N4-(9-fluorenylmethoxycarbonyl)cytallene (11c) using vinyl butyrate or acetate catalyzed by lipases in organic solvents was investigated.Reactions with 1b, 11a, and adenallene (1a) did not display a high enantioselectivity but all resulted in a predominant acylation of the (-)-enantiomers.Application of the Lowe-Brewster rule led to a tentative assignment of the R-configuration to all acylated products.Studies of the time course of acylation of (+/-)-N4-benzoylcytallene (11b) in chloroform, tetrahydrofuran (THF), tetrahydropyran (THP), tetrahydrothiophene (THT), and dioxane with lipase PS30 and/or AK showed that the reaction in THF catalyzed by lipase AK was the most promising for resolution of 11b.Indeed, a large-scale acylation afforded, after separation and deprotection of intermediates 3e and 10d, (+)- and (-)-cytallene (3c and 2b) in high yield and enantioselectivity.Acylation of 11c in THF led also to formation of 3c and 2b in high enantioselectivity.Single crystal X-ray diffraction established the S-configuration of (+)-cytallene (3c), thus confirming the assignment made on the basis of Lowe-Brewster rule.An improved large-scale synthesis of (+/-)-cytallene (1b) is also described.The R-enantiomer 2b inhibited the replication of a primary human immunodeficiency virus (HIV-1) isolate in phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBM) with IC50 0.4 and IC90 1.7 μM. (+/-)-Cytallene (1b) exhibited IC50 0.8 and IC90 3.4 μM.Both compounds completely suppressed replication of HIV-1 at 10 μM with no detecable cytotoxicity.The S-enantiomer (3c) was inactive.
Nucleic Acid Derived Allenols: Unusual Analogues of Nucleosides with Antiretroviral Activity
Phadtare, Shashikant,Zemlicka, Jiri
, p. 5925 - 5931 (2007/10/02)
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.
