Khellin

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

KF 17837 [141807-96-7] K7 fluid [59884-34-3] KFM19 [133058-72-7] Kharasch process Khellin [82-02-0] Khesari... 

Many 1,2,3,5-benzenetetrol derivatives are used mediciaaHy. For example, khellin [82-02-0] (65), which is a naturally occurring benzopyranone, is used as a coronary vasodilator and bronchodilator (233). Derivatives of khellin are effective local anesthetics and antiarrythmics (234). Similarly, amine derivatives (68) that are prepared from khellinone oxime (66) exhibit hypnotic, sedative, anticonvulsant, antiinflammatory, cardiac analeptic, diuretic, and antiulcerous activity (235) (see Analgesics, antipyretics, and antiinflammatory agents). 

Khellin (4,9-dimethoxy-7-methyl-5-oxofuro[3,2-g]-l,2-chromene) [82-02-0] M 260.3, m 154-155 , b 180-200 /0.05mm. Crystd from MeOH or diethyl ether. 

Khellin is a natural product closely related to the psoralens in which a chromone ring has been substituted for the cou-marin. The plant material has been used since ancient times as a folk remedy modern pharmacologic work has confirmed the bronchio-dilating and antispasmodic activity of khellin. The synthesis outlined below, it should be noted, is selected from a half-dozen or so reported within the last quarter century. 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

Athmakhell (Steigerwald) Farctil (Gewo) wfm F Khelline Promethazine... 

Price, R., Gaber, B. and Lvov, Y. (2001) In-vitro release characteristics of tetracycline, khellin and nicotinamide adenine dinudeotide from halloysite a cylindrical mineral for delivery of biologically active agents. Journal of Microencapsulation, 18, 713—723. 

Khellin (32) Cromolyn sodium (33) Chromone derivative Vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis... 

Initial observations on khellin (32), a furochromone-type compound from Ammi visnaga L., showed a mast-cell stabilizing effect. This led to the synthesis of many derivatives of this lead for the potential treatment of allergy and asthma, most notably the approved preventive antiasthma drug, cromolyn sodium (33). The precise molecular mechanism of this class of drugs is not yet clearly imderstood. ... 

Another khellin-inspired benzofuran is the cardiotonic and vasodilating Agent, benfurodil (84)... 

In 1962, Pierre Eymard, a graduate smdent at the University of Lyon, synthesized a series of khellin derivatives. Khellin is a biologically active substance that occurs in the fruit of the wild Arabian Khell plant and which has been used for centuries by herbalists for the treatment of kidney stones. Eymard arranged to have his new compounds biologically evaluated at the Ecole de Medecine et de Pharmacie in nearby Grenoble. When attempts to produce a solution of these khellin compounds failed, advice was sought from H. Meunier of the nearby Laboratoire Berthier. In view of Berthier s recent peripheral interest in valproic acid as a solvent for bismuth compounds, Meunier recommended valproic acid as a nontoxic inert solvent. 

Eymard s khellin derivatives were dissolved in valproic acid and, following the practice of submitting all such compounds for evaluation in an antiepileptic screening model, they were studied for anticonvulsant activity. These preliminary studies revealed profound anticonvulsant activity. Shortly after this, Meunier serendipitously decided to use valproic acid as a solvent for an unrelated coumarin compound and, although chemically dissimilar to Eymard s khellins, this coumarin exhibited identical anticonvulsant properties. The fact that both compounds had been dissolved in the same solvent was realized immediately. The antiepileptic action of valproic acid was thus discovered completely by accident, with the first successful clinical trial occurring in 1963. 

The furanochromone khellin (43) from the seeds of Ammi visnaga is a coronary vasodilator, and it has long been used in Egypt as a spasmolytic to relieve renal colic and ureteral spasms due to schistosomiasis. The corresponding dihydroxy compound is also a vasodilator, but other related compounds are inactive (5lCRV(48)543). 

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