NEOFLAVONOIDS
eof lavono
The term neoflavonoid is reserved for C15 compounds of the Ar-C3-Ar type, structurally related to flavonoids and isoflavonoids and constructed on a 1,1-di-phenylpropane skeleton. Like 2- and 3-phenylchromanes, they arise from the condensation of three acetate molecules with one cinnamate molecule, but their mechanism of formation is very different. It is possible (but this is only a hypothesis) that they result from the (SN2') reaction of a phenol such as phloroglucinol or resorcinol with the a-carbon of the side chain of a phenylpropane unit.
The vast majority of known neoflavonoids has been isolated from the Fabaceae {Dalbergia) and Clusiaceae (Lindley = Guttiferae Juss.: Calophyllum, Mammea, Mesua). Some are also found in the Rubiaceae (Coutarea) and Asteraceae (Echinops).
The group comprises 4-arylcoumarins (4-aryl-2//-l-benzopyran-2-ones), 3,4-dihydro-4-arylcoumarins such as the calomelanols of Pityrogramma calomelanos (L.) Link (Pteridaceae) *, neoflavenes, 3-arylbenzo[b]furans, and "open" compounds: dalbergiones, dalbergiquinols, and benzophenones.
The various representatives of the neoflavonoid group have no distinct biological properties. However, we shall cite here the Calophyllum "balsam", even though there are apparently no studies to link the healing properties attributed to it to the 4-arylcoumarins that it contains.
CH3o
(S)-4-Methoxydalbergione
* The 3,4-dihydro-4-aryIcoumarins described in Cinchona succirubra (cinchonains) are
vipwp.H mni'p     flavan dpnvntivps rpp tannin <:n!.-tm\'
Dalbergiones, dalbergiquinols, and related products are responsible for the dermatitis caused, especially in wood workers, by the various species of Brazilian rosewood: Dalbergia melanoxylon Guillemin & Perrottet, D. retusa Hemsley, D. nigra (Veil. Cone.) Benth., D. latifolia Roxb... as well as Machaeriwn scleroxylum Tul. (see quinone-containing drugs).
• India Poon,
Calophyllum inophyllum L., Clusiaceae
The "beauty-leaf mastwood" tree is found in southeast Asia and from Madagascar to Polynesia. It is used for its oil-rich drupe-like fruit. By expression, this fruit provides a pasty mass, improperly called balsam, rich in triacylglycerols, and containing several 4-arylcoumarin-type derivatives, including calophyllolide, inophyllolide, and cw-dihydroinophyllolide. Reputed as a healing and antiulcer agent, the balsam was marketed in France for ages as a healing and analgesic agent for the treatment of burns. It is still listed in the product suppliers' catalog, for cosmetic applications.
In 1992, the antiviral properties of calanolides— 4-aryl and 4-alkyl coumarins isolated from a variety of C. lanigerum Miq. from Sarawak—were shown and this spurred renewed interest in this genus. Like the calanolides, most of the other derivatives in this group (soulattrolide of C. teysmanii Miq., costatolide) are reverse transcriptase inhibitors and inhibitors of the cytopathogenicity of HIV-1 in vitro, including for strains resistant to AZT. Their unusual mechanism of action, which involves two different sites, makes them the prototypes of a novel class of non-nucleosidic reverse transcriptase inhibitors.
BIBLIOGRAPHY
Donnelly, D.M.X. and Boland, G. (1994). Neoflavonoids, in "The Flavonoids: Advances in Research since 1986", (Harborne, J.B., Ed.), p. 239-258, Chapman & Hall, London.
Currens, M.J,, Gulakowski, R.J., Mariner, J.M., Moran, R.A., Buckeit, R.W., Gustavson, K.R.. McMahon, J.B. and Boyd, M.R. (1996). Antiviral Activity and Mechanism of Action of Calanolide A against the Human Immunodeficiency Virus Type-1, J. Pharmacol. Exp. The^279, 645-651.
McKee, T.C., Covington, CD., Fuller, R.W., Bokesch, H.R., Young, S., Cardellina, J.H., Kadushin, M.R., Soejarto, D.D., Stevens, P.F., Cragg, G.M. and Boyd, M.R. (1998). Pyranocoumarins from Tropical Species of the Genus Calophyllum: A Chemotaxonomic Study of Extracts in the National Cancer Institute Collection, J. Nat. Prod., 61, 1252-1256.
Zembower, D.E., Liao, S., Flavin, MT., Xu, Z.-Q., Stop, T.L., Buckheit, R.W., Klnlevich, A., Mar, A.A. and Sheinkman, A.K. (1997). Structural Analogues of the Calanolide Anti-HIV Agents. Modification of the trans-\0,\l-Dimethyldihydropyran-12-ol Ring (Ring C), J. Med. Chem., 40, 1005-1017.