Chemically synthesized naringenin derivatives, identical to natural occurring compounds, were tested for their estrogenic activity using two independent estrogen screening assays. Using a yeast based estrogen receptor assay, strong estrogenic activities were demonstrated for 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin, while the parent compound naringenin did not show recognizable estrogenic activity. In MVLN cells, a bioluminescent MCF-7-derived cell line, the estrogenic activity of 8-prenylnaringenin and 6-(1,1-dimethylallyl)naringenin was detected at concentrations of 10(-6) M and 5 x 10(-6) M respectively. Naringenin demonstrated estrogenic activity but only at a concentration of 10(-5) M. These estrogenic effects are mediated by the ER, as the antiestrogen 4-hydroxytamoxifen inhibited these activities. In summary, this study provides the further confirmation that 8-prenylnaringenin demonstrates high estrogenic activity, and demonstrated for the first time for 6-(1,1-dimethylallyl)naringenin a reasonable high estrogenic activity, while naringenin exhibit low or no estrogenic activity.

This article is available online at http://dmd.aspetjournals.org ABSTRACT:The female flowers of hops are used throughout the world as a flavoring agent for beer. Recently, there has been increasing interest in the potential estrogenic properties of hop extracts. Among the possible estrogenic compounds in hops, 8-prenylnaringenin is perhaps most significant due to its high in vitro potency exceeding that of other known phytoestrogens. Since data regarding the pharmacokinetic properties of this compound are lacking, we investigated the in vitro metabolism of 8-prenylnaringenin by human liver microsomes. A total of 12 metabolites were identified, and biotransformation occurred on the prenyl group and the flavanone skeleton. The major site of oxidation was on the terminal methyl groups, and of the two possible isomers, the trans isomer was more abundant. The double bond on the prenyl group was also oxidized to an epoxide that was opened by intramolecular reaction with the neighboring hydroxyl group. On the flavanone skeleton, the major site of oxidation was at 3 position on the B ring. Other metabolites included oxidation at carbon-3 as well as desaturation of the C ring to produce 8-prenylapigenin. An unusual hydroxy quinone product formed by ipso hydroxylation of the B ring of 8-prenylnaringenin was also detected. This product was probably an intermediate for the B ring cleavage product, 8-prenylchromone.

Treatment of [Cp 2 TiCH 3 (thf) + ] (5, with [BPh 4 -] anion) with 1,3-diisopropylimidazol-2ylidene (4) at ambient temperature resulted in a rapid displacement of the thf ligand by the stable heterocyclic carbene to yield the Arduengo carbene methyltitanocene cation complex 6a (>90% isolated). The X-ray crystal structure analysis of 6a showed that the heteroatomstabilized carbene ligand [d(Ti-C(carbene) ) 2.289(2) Å, d(Ti-CH 3 ) ) 2.178(3) Å] was bonded to titanium in an orientation where the imidazol-2-ylidene ring lies in the major σ-ligand plane of the bent metallocene moiety. A DFT calculation of 6a and a series of related model compounds has revealed that the Arduengo carbene serves as a pure σ-donor ligand to the titanocene moiety. The observed favored "in-plane" orientation of the ligand is steric in origin. Consequently, complex 6a attains an analogous C s -symmetric structure in solution, featuring symmetry-equivalent Cp rings and a pair of diastereotopic isopropyl substituents as well as chemically differentiated imidazol-2-ylidene C 4 HdC 5 H groups. The reaction of the ion pair [(Cp 2 ZrCH 3 ) + (CH 3 B(C 6 F 5 ) 3 -] (7) with 4 gave the analogous Arduengo carbene zirconocene cation complex 6b (>95% isolated, with [CH 3 B(C 6 F 5 ) 3 -] anion).

A surprisingly selective, non-enzymatic kinetic resolution of readily available, racemic β-chiral ketones enabled the title process, which was applied to a rapid synthesis of several bioactive flavanones in virtually enantiopure form (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl).

Dedicated to Prof. Johann Mulzer, an inspiring teacher of organic chemistry, on the occasion of his 60 th birthday. Abstract:The catalytic asymmetric Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers that contain two stereogenic double bonds is described. A combination of the highly Lewis acidic [Cu{(S,S)-tert-Bu-box}](H 2 O) 2 (SbF 6 ) 2 complex and molecular sieves served as catalyst and afforded the Claisen rearrangement products, substituted and functionalized a-keto esters, in high yield with a remarkable diastereo-and enantioselectivity. The influence of ligand structure, counterion and allyl vinyl ether double bond configuration on the stereoselectivity of the rearrangement was briefly investigated. We propose an explanation for the rate accelerating effect of the Lewis acid as well as a stereochemical model which serve to explain and predict the stereochemical course of the copper bis(oxazoline) catalyzed Claisen rearrangement.