Journal ArticleDOI
Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (±)-calanolide A and its enantiomers
Michael T. Flavin,John D. Rizzo,Albert Khilevich,Alla Kucherenko,Abram Kivovich Sheinkman,Vilayphone Vilaychack,Lin Lin,Wei Chen,Eugenia Mata Greenwood,Thitima Pengsuparp,John M. Pezzuto,Stephen H. Hughes,Thomas M. Flavin,Michael Cibulski,William A. Boulanger,Robert L. Shone,Ze-Qi Xu +16 more
Reads0
Chats0
TLDR
The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol, which includes Pechmann reaction, Friedel-Crafts acylation, chromenylation with 4,4-dimethoxy- 2-methylbutan-2-ol, cyclization, and Luche reduction.Abstract:
The anti-HIV agent (±)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol [→ 5 → 6 → 11 → 18 → (±)-1], which includes Pechmann reaction, Friedel−Crafts acylation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclization, and Luche reduction. Cyclization of chromene 11 to chromanone 18 was achieved by employing either acetaldehyde diethyl acetal or paraldehyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luche reduction of chromanone 18 at lower temperature preferably yielded (±)-1. Reduction of chromone 12, synthesized by Kostanecki−Robinson reaction from chromene 11, failed to afford (±)-1. The synthetic (±)-1 has been chromatographically resolved into its optically active forms, (+)- and (−)-1. The anti-HIV activities for synthetic (±)-1, as well as resultant (+)- and (−)-1, have been determined. Only (+)-1 accounted for anti-HIV activity, which was similar to the data reported for the natural product, and (−)-1 was inactive.read more
Citations
More filters
Journal ArticleDOI
Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy HIV-negative volunteers.
David A. Eiznhamer,Terri Creagh,Jon L. Ruckle,Dwain T. Tolbert,Jeremy Giltner,Bipul Dutta,Michael T. Flavin,Tuah R. Jenta,Ze-Qi Xu +8 more
TL;DR: These pharmacokinetic properties, together with the benign safety profile, and unique in vitro resistance pattern warrant the continued development of this potential new antiviral agent.
Journal ArticleDOI
(CTA)3[SiW12]–Li+–MMT: a novel, efficient and simple nanocatalyst for facile and one-pot access to diverse and densely functionalized 2-amino-4H-chromene derivatives via an eco-friendly multicomponent reaction in water
TL;DR: In this paper, a simple, facile and highly efficient one-pot synthesis of a pharmaceutically interesting diverse kind of functionalized 2-amino-4H-chromene by a straightforward three-component reaction of an aromatic aldehyde, malononitrile (or ethyl cyanoacetate) and diverse enolizable C-H activated acidic compounds in the presence of a catalytic amount of (CTA)3[SiW12]−Li+−MMT is reported as a novel, environmentally friendly, reusable and promising nanocat
Journal ArticleDOI
[Bmim]BF4: A Versatile Ionic Liquid for the Synthesis of Diverse Bioactive Heterocycles
Journal ArticleDOI
Synthetic Developments in Functionalized Pyrano[2,3-c]pyrazoles. A Review
Bekington Myrboh,Hormi Mecadon,Md. Rumum Rohman,Mantu Rajbangshi,Icydora Kharkongor,Badaker M. Laloo,Iadeishisha Kharbangar,Baskhemlang Kshiar +7 more
TL;DR: The pyran ring and its derivatives have been and continue to be a subject of considerable importance due to their wide spectrum of biological applications as mentioned in this paper, and they have been used in many applications.
Journal ArticleDOI
Phenolics with Anti-HSV and Anti-HIV Activities from Artocarpus gomezianus., Mallotus pallidus., and Triphasia trifolia.
Kittisak Likhitwitayawuid,Butsarakham Supudompol,Boonchoo Sritularak,Vimolmas Lipipun,K. Rapp,Raymond F. Schinazi +5 more
TL;DR: The data obtained in this study suggest the bis-hydroxyphenyl structure as a potential target for anti-HSV and HIV drugs development.
References
More filters
Journal ArticleDOI
Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.
TL;DR: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer.
Journal ArticleDOI
HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy
TL;DR: It would be premature to alter any treatment protocols for HIV-infected individuals at present, as it cannot be determined from this small sample of patients whether development of a less sensitive virus phenotype results in clinical resistance.
Journal ArticleDOI
Lanthanoids in organic synthesis. 6. Reduction of .alpha.-enones by sodium borohydride in the presence of lanthanoid chlorides: synthetic and mechanistic aspects
Andre L. Gemal,Jean Louis Luche +1 more
Journal ArticleDOI
Molecular targets for AIDS therapy
TL;DR: In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.
Journal ArticleDOI
New Soluble-Formazan Assay for HIV-1 Cytopathic Effects: Application to High-Flux Screening of Synthetic and Natural Products for AIDS-Antiviral Activity
Owen S. Weislow,Rebecca Kiser,Donald L. Fine,John P. Bader,Robert H. Shoemaker,Michael R. Boyd +5 more
TL;DR: In this paper, an effective and optimally safe microculture method for rapid and convenient assay of the in vitro cytopathic effects of human immunodeficiency virus (HIV-1) on human lymphoblastoid or other suitable host cells.