Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers. NLM AIDSLINE Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

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Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers.

J Med Chem. 1996 Mar 15;39(6):1303-13. Unique Identifier : AIDSLINE MED/96251034
Flavin MT; Rizzo JD; Khilevich A; Kucherenko A; Sheinkman AK; Vilaychack V; Lin L; Chen W; Greenwood EM; Pengsuparp T; Pezzuto JM; Hughes SH; Flavin TM; Cibulski M; Boulanger WA; Shone RL; Xu ZQ; MediChem Research, Inc., Lemont, Illinois 60439, USA.

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.
Keywords: Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY Chromatography, High Pressure Liquid Coumarins/ANALYSIS/*CHEMICAL SYNTHESIS/PHARMACOLOGY DNA Polymerases/ANTAGONISTS & INHIB HIV/*DRUG EFFECTS RNA-Directed DNA Polymerase Stereoisomers Support, U.S. Gov't, P.H.S. JOURNAL ARTICLEKWDantiviralagents/KWDchemicalsynthesis/pharmacologychromatography,highpressureliquidcoumarins/analysis/KWDchemicalsynthesis/pharmacologydnapolymerases/antagonists&inhibhiv/KWDdrugeffectsrna-directeddnapolymerasestereoisomerssupport,uKWDsKWDgov't,pKWDhKWDsKWDjournalarticle
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