Mass spectrometry studies of iridoid aglycone derivatives

C. R. PUNGITORE; C. GARCIA; V. S. MARTIN; C. E. TONN ; C. E. ARDANAZ

RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM.

JOHN WILEY & SONS LTD

Lugar: Londres; Año: 2011 vol. 25 p. 2099 - 2105

0951-4198

Iridoid (cyclopentane[c]pyranomonoterpenoids) glycosides are present in about 57 families of plants and form a collection of almost 600 structures which have an important role in chemotaxonomy.[1,2] Several biological activities for this kind of compounds and iridoid‐containing plants have been reported, such as antimicrobial, antitumoral, hemody- namic, choleretic, hepatoprotective and anti‐inflammatory activities.[3–6] The iridoid catalpol (1) demonstrates a certain resemblance to a nucleoside framework (Fig. 1). The bicyclic aglycone possibly will mimic the purine scaffold present in nucleosides. In vitro, the iridoid catalpol (1) has shown significant inhibition of Taq DNA polymerase.[7] DNA polymerases represent important cellular targets in the development of anticancer and antiviral agents. In addition, we have determined, in previous studies, that the aglycone fragment of catalpol plays a relevant rol in Taq DNA inhibition.[7,8] Furthermore, we have previously synthesized the bicyclic aglycone derivatives by means of a cyclization reaction catalyzed by L‐proline.[9] These compounds repre- sent a simplified scaffold of the aglycone framework of naturally occurring iridoids, and their silylated derivatives showed remarkable biological activity towards human cancer cell lines, including cell cycle arrest and apoptosis induction. Therefore, they could be used as therapeutic compounds for treatment of cancer, either alone or in combination. These results are consistent with literature showing that silyl ethers addition represents a plausible strategy to introduce lipophilicity‐improving drug activity.[10–13] In the present work, we report and discuss the electron ionization mass spectrometry (EI‐MS) (Low Resolution) and collision‐induced dissociation tandem mass spectrometry (CID‐ MS/MS) fragmentation of a iridoid aglycone silylated de- rivative, namely 5‐((tert‐butyldiphenylsilyl)oxy)‐7‐methyl‐ 1,4a,5,6,7,7a‐hexahydrocyclopenta[c]pyran‐1‐yl acetate (2). In addition the use of EI‐high‐resolution mass spectrometry (EI‐HRMS) and high‐performance liquid chromatography/ electrospray ionization mass spectrometry (HPLC/ESI‐MS) allowed us to describe in detail the fragmentation pathways in several ionization modes.