Syntheses of antifungal isocoumarins. II. Synthesis and antifungal activity of 3-substituted isocoumarins.

2003

Helvetica Chimica Acta

A short stereoselective synthesis of (3R) -3,4-dihydro-6,8-dimethoxy-3-undecyl-1H-[2]benzopyran-1-one and derivatives isolated from Ononis natrix has been described. Condensation of dodecanoyl chloride with 3,5-dimethoxyhomophthalic acid afforded 6,8-dimethoxy-3-undecylisocoumarin 3, which, on sequential saponification and esterification, yielded the keto ester 5. Enantioselective reduction of 5 with TarB-NO 2 /LiBH 4 directly furnished the title dihydroisocoumarin 1a in 80% ee (82% yield). Partial as well as complete demethylation of the latter provided the dihydroisocoumarins 1b and 1c, respectively. Diastereotopy of the CH 2 H-atoms on either side of the stereogenic center (C(3)) and the mass-fragmentation pattern of the dihydroisocoumarins have also been described. All of the compounds synthesized were examined in vitro for antifungal activity.

“…EI-MS: 378 (27. 8 Methyl 4,6-Dimethoxy-2-(2-oxotridecyl)benzoate (5). A mixture of 4 (0.25 g, 0.66 mmol) and anh.…”

Section: Experimental Partmentioning

confidence: 99%

mentioning

confidence: 99%

Stereoselective Synthesis of (3R)‐3,4‐Dihydro‐6,8‐dimethoxy‐3‐undecyl‐ 1H‐[2]benzopyran‐1‐one and Derivatives, Metabolites from Ononis natrix

2003

Helvetica Chimica Acta

“…Direct condensation of acid chlorides with homophthalic acids has recently been proved to be an authentic route for the construction of 3-substituted isocoumarin skeleton [18], therefore synthesis of phenylacetic acid on one hand and that of homophthalic acid on the other is of enormous practical importance.…”

Section: Introductionmentioning

confidence: 99%

An efficient synthesis of 3,5‐dimethoxyhomophthalic acid, a key intermediate for synthesis of natural isocoumarins

Journal of Heterocyclic Chem

Rama

Arfan

2003

“…The limited quantities available from natural sources together with the possibility of preparing analogues with improved biological activities show the imperative need for the total synthesis. The condensation of acid chlorides with homophthalic acid has recently emerged as a standard and authentic route for the preparation of the 3-substituted isocoumarin skeleton [17][18][19]. Herein a short and efficient synthesis of xyridins A and B achieved employing this method and the conversion of the former into corresponding the (±)-3,4-dihydroisocoumarin will be described.…”

mentioning

confidence: 99%

A Single-Step Synthesis of Xyridins A and B, Metabolites from Xyris indica

2005

Chem Heterocycl Compd

A facile single-step synthesis of the title isocoumarins isolated from Xyris indica has been elaborated. Condensation of butanoyl chloride and 2-oxobutanoyl chloride with 3,4-methylenedioxyhomophthalic acid afforded xyridin A and xyridin B, respectively. Xyridin A was saponified to the corresponding keto acid, which on reduction gave the (±)-3,4-dihydro-6,7-methylenedioxy-3-propylisocoumarin in which diastereotopy of the methylenic protons around the stereogenic center was observed. A mass fragmentation mechanism for xyridins has also been suggested.In 1995, Ruangrungsi et al. isolated from the nonpolar fraction of the chloroform extract of the flowering heads of the weed Xyris indica two new isocoumarins, which they named xyridins A and B [1]. Xyris indica L. (tall yellow-eyed grass) is one of the five species of the genus Xyris found throughout Thailand and is known locally as "Kra thin thung". In Bengal the plant has been used in folk medicine as a cure for ring worm, itch, and leprosy. The structures of xyridin A and B were established by modern spectroscopic techniques as 6,7-methylenedioxy-3-propylisocoumarin (1a) and 6,7-methylenedioxy-3-(1-oxopropyl)isocoumarin (1b), respectively. O O O O X 1a,b 1 a X = H 2 , b X = OAlthough xyridins A and B, like the majority of other naturally occurring isocoumarins derived biogenetically from acetate via the acetate-polymalonate pathway, possess a C(8) or C(6) and C(8) oxygenation, xyridins A and B are unique in being 3-alkyl/acyl-substituted 6,7-methylenedioxyisocoumarins. In the literature unsubstituted 4,5-, 6,7-methylenedioxyisocoumarins and 4,5-, 5,6-, 6,7-methylenedioxy-3,4-dihydroisocoumarins are known along with 3-methyl-6,7-methylenedioxy-3,4-dihydroisocoumarin as the only example of a 3-alkyl-substituted 6,7-methylenedioxyisocoumarin [2][3][4]. Some important examples of other natural products bearing a 6,7-methylenedioxydihydroisocoumarin moiety are hippeastrine [5], tetrabenzylcorricidin [6], lycoricidin [7], pancratistatin [8,9], and tazettine [10]. Peshawarine contains an 3-aryl-7,8-methylenedioxy-3,4-dihydroisocoumarin skeleton [11]. __________________________________________________________________________________________