Synthesis of dual 14C-labeled (+)-calanolide A, a naturally occurring anti-HIV agent

Abstract

[10,18‐14C]‐(+)‐Calanolide A [(+)‐6] was synthesized in four steps from chromeno‐coumarin 2. A Ti‐mediated aldol reaction of 2 with [1,2‐14C]‐acetaldehyde stereoselectively produced the desired syn diastereomer (±)‐3, with carbons at the 13 and 14 positions being 14C‐labeled. Intermediate (+)‐3 was isolated by lipase‐catalyzed kinetic resolution and cyclized under Mitsunobu conditions to afford (+)‐trans‐2,3‐dimethyl chroman‐4‐one, (+)‐5. Luche reduction on (+)‐5 in EtOH/THF at −78°C led to the formation of dual 14C‐labeled (+)‐6 with a specific activity of 49.25 mCi/mmol. The overall radiochemical yield was 4.3% based on the starting 14C‐acetaldehyde. © 1997 John Wiley & Sons, Ltd.

Coumarins as anti-HIV agent and correlation with COVID-19: an overview

“…Additionally, an in vitro study was performed on anti-viral action against HIV for derivative of coumarine (+)-, (−)-, and (+/−)-12-oxocalanolide A (Figure 4), and found inhibitors of HIV-1 reverse transcriptase showing strong action against number of viruses chosen for resistance to other HIV-1 non-nucleoside RT inhibitors. This is the first study to report information that calanolide analogue is also able to inhibit such activity [27,28].…”

Mitsunobu and Related Reactions: Advances and Applications

“…The author has pointed out that the specific rotation of the synthetic ( S )-2,6-dimethylchroman-4-one was higher than that for the natural product. The intermediates 2-methyl- and 2,3-dimethylchromanones required for (+)-calanolide A, an anti-HIV agent, were prepared by a Mitsunobu intramolecular cyclization. − Other applications leading to six-membered heterocycles involve (i) heliquinomycinone reported by Danishefsky and co-workers, (ii) functionalized steroid-like molecules reported by Yus and co-workers, and (iii) the structural elucidation of capituloside reported by Zhou and co-workers…”

“…This compound and its analogues have been claimed to be useful in treating tuberculosis. Mitsunobu ether formation cum cyclization prior to reduction of a keto group was one of the key steps in the synthetic strategy, as shown in Scheme a; − related work has been published earlier. − The macrocyclization in the case of 659 was also accomplished by a Mitsunobu etherification as shown in Scheme b . Some of these cyclized peptide derivatives are inhibitors of matrix metalloproteinases and tumor necrosis factor α secretion.…”

“…The intermediates 2-methyl-and 2,3-dimethylchromanones required for (+)-calanolide A, an anti-HIV agent, were prepared by a Mitsunobu intramolecular cyclization. [732][733][734] Other applications leading to six-membered heterocycles involve (i) heliquinomycinone reported by Danishefsky and co-workers, 735 (ii) functionalized steroid-like molecules reported by Yus and co-workers, 736 and (iii) the structural elucidation of capituloside reported by Zhou and coworkers. 737 The electron-poor benzopyran 226 could be obtained via intramolecular cyclization using a Mitsunobu protocol (Scheme 55a).…”

Molecular Iodine Mediated One Step Synthesis of 3-Substituted-6-(6-Substituted-2-Oxochromen-3-yl)-7H [1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

“…Enormous number of compounds bearing coumarin system in their structure have been synthesised and these derivatives have shown a remarkably broad spectrum of pharmacological activities and they have been used as anticoagulant, 1-3 antibacterial, 4,5 antiviral, 6,7 antitumor, [8][9][10][11] bactericidal, 12 fungicidal 13 and anti-inflammatory agents. 14 Also, in recent times there are reports regarding anti-HIV activity [15][16][17][18] of coumarin derivatives. Coumarins linked with nitrogen/nitrogen and sulfur heterocyclic units at 3-position are well known to exhibit spasmolytic, 19 uricosuric, 19 anticancer 20 and antitubercular activitiy.…”