Lithospermic acids

Scheme 5.13. Total synthesis of (-l-)-lithospermic acid via C—H bond activation.

N.A. Lithospermic acid.100 Used as a form of birth control, prevent gonadotrophin from stimulating ovaries in lab mice. 

Lithospermic acid (phenylpropanoid, caffeic acid trimer, benzofuran)... 

Lithospermic acid Cnicus benedictus (Asteraceae), AC (AO/FRS, ProH)... 

Aromatic C-H bond activation opens an attractive pathway to achieve cyclizations with tethered alkenes for the synthesis of dihydrobenzofurans <2001JA%92> <20030L1301>. An auxiliary-directed asymmetric alkylation via C-H bond activation to yield a virtually enantiomerically pure 2,3-enantioselective synthesis of (-l-)-lithospermic acid has been reported by Bergman, Ellman, and co-workers (Scheme 97) <2005JA134%>. 

Phenolic acids include the benzoic acids (Ce-Ci), e.g., gallic, vanillic, syringic, protocatechuic, p-hydroxy-benzoic acid, as well as cinnamic acids (C6-C3), e.g., caffeic, p-coumaric, ferulic, sinapic acids, and their dep-sides and derivates, e.g., rosmarinic acid and lithospermic acid (Fig. 1). Phenolic acids and flavonoids in plants may occur in the free form, but they are often glycosylated with various sugars, especially glucose. Phenolic acids may also be present in the esterified as well as bound forms. Free phenolic acids are found especially in herbs and spices and, very often, in compounds responsible for antioxidant activity (benzoic and cinnamic acids and some of their derivatives). The bound forms are more common for the fruits, vegetables, and other plant materials. Therefore, in some cases, it is necessary to combine the analysis of their free and bound forms. 

Yuan, J.P. Chen, H. Chen, P. Simultaneous determination of rosmarinic acid, lithospermic acid B and related phenolics in Salvia miltiorrhiza by HPLC. J. Agric. Food Chem. 1998, 46, 2651-2654. 

An efficient asymmetric synthesis of substituted methyl 2-aryl-dihydrobenzo[h]furan-3-carlx)xylate was achieved by a rhodium-catalyzed C-H bond activation route in an excellent yield, and the generated product was an intermediate applicable to the total synthesis of (+)-lithospermic acid <0 A13496>. A similar type of framework existing in ( )-E-viniferin was m e through a biomimetic transformation by a T1(N03)3-mediated oxidative dimerization of resveratrol <05T10285>. 

They are generally active at the two steps of the integration but are not selective for IN and the practical utility of those catechol-containing inhibitors is severely reduced by cytotoxicity even though they have been found to inhibit HIV-1 integrase in vitro. Nevertheless, lithospermic acids, Fig. (19) were found to be active on purified IN as well as on HIV-1 infected H9 cells, and showed no cytotoxicity to H9 cells [80]. 

Blessed thistle is reported to contain lithospermic acid, a compound with antigonadotropic activity (Graham and Noble 1955). 

Scheme 5.42 Total synthesis of (+)-lithospermic acid reported by Bergman and Ellman.

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