Within the flavonoid class of natural products the prenylated sub-class is quite rich in structural variety and pharmacological activity. In the last twenty years a huge number of new structures has been reported, mostly from Leguminosae and Moraceae, with few coming from other genera. The presence, in different forms, of the isoprenoid chain can lead to impressive changes in biological activity, mostly attributed to an increased affinity for biological membranes and to an improved interaction with proteins. Molecules, such as xanthohumol and sophoraflavanone G, while being very structurally simple, show numerous pharmacological applications and are ideal candidates for SAR aimed to the discovery of new drugs. Only recently the biogenesis of these compounds has been more extensively studied and much attention has been focused on the enzymes involved in the modification and transfer of the prenyl unit.

Treatment of (E)-2,4-dimethoxycinnamic acid methyl ester with BF3.Et2O in CHCl3 at room temperature afforded in 75% yield two stereoisomeric C-alkylcalix[4]resorcinarenes, which were shown to be in the 1,2-alternate and flattened-cone configurations

Resorc[4]arene octamethyl ethers 1-3, when treated with NOBF4 salt in chloroform, form very stable 1:1 nitrosonium (NO+) complexes, which are deeply colored. The complexation process is reversible, and the complexes dissociate and bleach upon addition of methanol or water, to give the starting macrocycles. Resorc[4]arenes 1 and 2 are in the same cone conformation, but with different side-chains, whereas 3 possesses a different conformation (chair), while bearing the same side-chain as 2. Kinetic and spectral UV-visible analysis revealed that NO+ interacts with resorc[4]arenes 1 and 2 both outside and inside their basket, leading to complexes with two absorption patterns growing at different rates, one featuring high-energy bands (HEB) within the near-UV zone, and the other one low-energy bands (LEB), attributed to charge-transfer interactions, within the visible range. The presence of ester carbonyl groups in 2 strongly drives the NO+ cation outside the resorcarene. Resorc[4]arene 3 showed a spectral pattern pointing out a clear involvement of the ester moieties in the NO+ entrapping, beside the formation of significant charge-transfer interactions. 1H NMR spectroscopy and molecular modeling clearly supported these findings.

No abstract

Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-1b forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4- [(3-methyl-2-butenyl)-guanidino]butane. The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by i.v. route in anesthetized rats at doses ranging from 50 to 1600 micrograms/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta 1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.