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
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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
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Natural products to drugs: natural product derived compounds in clinical trials
Mark S. Butler,Mark S. Butler +1 more
TL;DR: Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural products for which clinical trials have been halted or discontinued since 2005.
Journal ArticleDOI
Natural product drug discovery in the next millennium.
Gordon M. Cragg,David J. Newman +1 more
TL;DR: By use of combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents.
Journal ArticleDOI
Recent progress in the development of coumarin derivatives as potent anti‐HIV agents
TL;DR: A dicamphanoyl‐khellactone analog, which was discovered and developed in the laboratory, and calanolide A are currently in preclinical studies and clinical trials, respectively.
Journal ArticleDOI
Twenty-Six Years of Anti-HIV Drug Discovery: Where Do We Stand and Where Do We Go?
Youcef Mehellou,Erik De Clercq +1 more
TL;DR: It is apparent that new anti-HIV drugs with acceptable toxicity and resistance profiles and, more importantly, new anti -HIV agents with novel mechanisms of action are clearly needed.
Journal ArticleDOI
Anti-HIV coumarins from calophyllum seed oil
TL;DR: Calophyllum cerasiferum contained (-)-calanolide B as its major coumarin constituent in significant amount and thus constitute a renewable source of this compound.
References
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The Action of Lithium Aluminum Hydride and Organometallic Reagents on 4-Hydroxycoumarin1
Journal ArticleDOI
Cyclization of the Enol Esters of o‐Acyloxyphenyl Alkyl Ketones, IV. A kinetic study of the steps of the KOSTANECKI‐ROBINSON reaction
TL;DR: In this paper, a study of the KOSTANECKI-ROBINSON reaction of 2,4-diacetoxy-6-hydroxy-propiophenone was performed and the rate constants and the order of each step were compared.
Journal ArticleDOI
Synthesis of 2,3-disubstituted chromones: cyclisation of the enolesters of o-acyloxyphenyl alkyl ketones
TL;DR: In this paper, a mechanism involving an intramolecular electrophilic addition between the enol double bond and the o-acyl group is suggested, and chromones have been prepared.