Sidoamidines – 8-(pyrrolidine-1-carboximidamide-2-yl)-(epi)gallocatechinsNew components in the Pelargonium sidoides extract EPs^® 7630

EPs^® 7630, a 15% hydroalcoholic Pelargonium sidoides extract, is used for the treatment of common cold, especially bronchitis. Minor ingredients are the plant-characteristic highly oxygenated benzopyranons, like umckalin in free and sulfated form, in addition to the major monomeric and oligomeric (epi)gallocatechins, the prodelphinidins (OPDs).

Detailed analysis of purified OPDs with 1D-and 2D-NMR (HSQC, HMPC) revealed a predominant 4->8 B-type connectivity of the monomeric units gallocatechin and epigallocatechin in about equal quantities. In addition to the plain OPD, another oligomer with an unusual additional substitution was detected, which was characterized by an added mass of 111 Da, leading to signals in the positive mass spectrum of (PES [M+H]⁺: 418, 722, 1026 Da; plain OPD: 307, 611, 915 Da). Isolation of one low content monomeric entity in combination with 2D-NMR spectroscopy revealed a pyrrolidine-1-carboximidamide-2-yl conjugation at the 8-position of (epi)gallocatechins. These substances were not reported yet, and are thus named as sidoamidines. Biomimetic syntheses of four pure isomers starting with (-)-gallocatechin and (-)-epigallocatechin, respectively, made it possible to establish their exact chemical structure by HRESIMS, 2D-NMR, and CD-spectroscopy [Fig. 1]. The chirality of the building blocks was unequivocally demonstrated by chiral chromatography and optical rotation of selected reference material.

Separation of the oligomeric sidoamidine fraction from plain OPD by cation exchange chromatography demonstrated quite similar structural characteristics (HSQC spectra) beside the extra substitution.

Evaluation of the new components in an animal disease model, the LPS induced sickness behavior, may argue for positive involvement in the (malady) treatment with EPs^® 7630.

Fig. 1 Constitution of sidoamidines with HMBC (green) and COSY (blue) correlations.