Malbrancheamides B and C, novel alkaloids from the fungus Malbranchea aurantiaca

Two new indole alkaloids, namely malbrancheamides B (1) [1] and C (2), were isolated from the culture medium and mycelia of the ascomycete Malbranchea aurantiaca, along with malbrancheamide (3). Structure elucidation of 1 and 2 was carried out by a combination of mass spectrometry (MS) and ¹H and ¹³C NMR spectroscopy analyses, as well as by comparison of the NMR data with those of 3 [2]. According to the conformational studies using molecular mechanics analyses, compounds 1 and 2 exist also in one preferred conformation, which was optimized by DFT B3LYP/G31G* level theory. Compound 1 is the second chlorinated indole alkaloid possessing a bicyclo [2.2.2] ring with an unusual relative configuration at C12a in the bicyclo [2.2.2] diazaoctane ring system. Biogenetically, the coexistence of compounds 1-3 suggests that 2 could undergo stepwise chlorination under the catalysis of an appropriate chlorperoxidase to yield first 3 and then 1. A docking analysis with 1-3 using AutoDock 4.0 [3] revealed that they interacted with CaM in the same pocket of trifluoropiperazine (TFP) and chlorpromazine (CZP).

Acknowledgements: CONACyT (fellowship), DGSCA (KanBalam system), Dr. Olson (AutoDock).

References: 1. Figueroa, M. et al. (2008) Nat. Prod. Res. in press.

2. Martínez-Luis, S. et al. (2006) Tetrahedron 1817–1822.

3. Morris, G.et al. (1998)J. Comp. Chem. 19: 1639–1662.