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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Journal ArticleDOI
Tailoring lipase specificity by solvent and substrate chemistries
TL;DR: An acyl binding structural model has been developed to explain the observed catalytic efficiencies and enantioselectivities of Candida rugosa lipase-catalyzed (trans)esterification reactions involving 2-hydroxy acids and vinyl esters, and acylation reactions involving both cyclic and acyclic alcohols.
Journal ArticleDOI
Total synthesis of (.+-.)-calanolide A, a non-nucleoside inhibitor of HIV-1 reverse transcriptase
TL;DR: The first synthesisation of (±)-calanolide A and the related (±)calanolides C and D have been carried out in a short sequence using a Lewis acid-promoted Claisen rearrangement to establish the chromene ring.
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Journal ArticleDOI
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Patrick K. Clark,A.L. Ferris,D.A. Miller,Amnon Hizi,K.-W. Kim,S.M. Deringer-Boyer,M.L. Mellini,Arthur D. Clark,Gail Ferstandig Arnold,W.B. Lebherz,Eddy Arnold,G.M. Muschik,Stephen H. Hughes +12 more
TL;DR: Fermentation conditions for the large-scale growth of the bacterial strain and a protocol for the purification of an enzymatically active 66-Kd form of the RT have been developed and the purified RT has all of the appropriate enzymatic functions and properties.
Journal ArticleDOI
Comparative anti-HIV evaluation of diverse HIV-1-specific reverse transcriptase inhibitor-resistant virus isolates demonstrates the existence of distinct phenotypic subgroups
Robert W. Buckheit,Valerie Fliakas-Boltz,William Decker,Joseph L. Roberson,Tracy L. Stup,C A Pyle,E L White,James B. McMahon,Michael J. Currens,Michael R. Boyd +9 more
TL;DR: Results indicate that the various subgroups of HIV-1-specific inhibitors interact differently with HIV- 1 RT, suggesting important potential implications for drug combination therapeutic strategies.