Phthalide

Abstract: A facile and enantioselective approach toward 3,4-dihydroisocoumarin was developed. The method involved an amino-thiocarbamate catalyzed enantioselective bromocyclization of styrene-type carboxylic acids, yielding 3-bromo-3,4-dihydroisocoumarins with good yields and ee's. 3-Bromo-3,4-dihydroisocoumarins are versatile building blocks for various dihydroisocoumarin derivatives in which the Br group can readily be modified to achieve biologically important 4-O-type and 4-N-type 3,4-dihydroisocoumarin systems. In addition, studies indicated that, by refining some parameters, the synthetically useful 5-exo phthalide products could be achieved with good yields and ee's.

Abstract: Coumarin, umbelliferone (7-hydroxycoumarin), scopoletin (7-hydroxy-6-methoxycoumarin), and limettin (5,7-dimethoxycoumarin), four naturally occurring plant constituents, were studied for their effects on 7,12-dimethylbenz(a)anthracene-induced neoplasia of the rat mammary gland. Coumarin was a moderately potent inhibitor, limettin was less effective, and scopoletin showed only marginal inhibitory activity. Umbelliferone did not inhibit. Coumarin and its three derivatives were also investigated for their effects on benzo(a)pyrene-induced neoplasia of the mouse forestomach. Coumarin inhibited, but the three derivatives did not. Coumaranone and phthalide, two related compounds, were inactive as were three substituted pyrones included in the study. Four five-membered ring lactones were also investigated. One of these, α-angelicalactone, inhibited benzo(a)pyrene-induced neoplasia of the mouse forestomach and was more potent in this regard than coumarin. The other three, γ-valerolactone, l-ascorbic acid, and isocitric lactone, were inactive. Three structure-activity relationships are evident from the present study. With the coumarins, increased polarity of substituents results in decreasing activity as inhibitors. For both the coumarins and the five-membered ring lactones studied, protic groups, such as hydroxy and carboxy groups, abolish the capacity to inhibit. While unsaturation in the lactone ring does not always lead to inhibitory activity, the presence of at least one double bond is essential. Thus, the property of inhibition of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene is not a general characteristic of all coumarins and alicyclic lactones but is restricted to those with specific structural features.

Abstract: Bioassay-guided fractionation of the chloroform extract from the roots of Angelica sinensis led to isolation and characterization of (Z)-ligustilide using direct-bioautography with Colletotrichum species. The structure of (Z)-ligustilide was confirmed by (1)H and (13)C NMR spectroscopy and GC/MS. (Z)-Ligustilide deterred the biting of two mosquito species more effectively than DEET. Three different A. sinensis accessions and one Angelica archangelica root oil were evauated by GC and GC/MS, and the dominant component in A. sinensis was 61-69% (Z)-ligustilide. Two other prominent compounds in A. sinensis oils were 5.7-9.8% (E)-3-butylidene phthalide and 1.5-2.3% (Z)-3-butylidene phthalide. The main constituents that comprised A. archangelica oil were monoterpene hydrocarbons such as 24.5% alpha-pinene, 13.8% delta-3-carene, 10.1% beta-phellandrene, 8.8% p-cymene, 8.4% limonene, and 6.3% sabinene. Phthalides and monoterpene hydrocarbons were determined to be good systematic markers or chemical fingerprints for A. sinensis and A. archangelica root oils. Chemical fingerprinting by GC/MS of A. sinensis also confirmed the misidentification of one A. archangelica sample sold in the Chinese market.

Abstract: Nine new fungal metabolites, one phthalide derivative, acremonide (1), and eight isocoumarin derivatives, acremonones A-H (2-9), were isolated from the mangrove-derived fungus Acremonium sp. PSU-MA70 together with 10 known compounds. Their structures were determined by NMR analysis. The known 8-deoxytrichothecin and trichodermol exhibited moderate antifungal activity against Candida albicans and Cryptococcus neoformanns, respectively.