
Bignoniaceae family
› 120 genera, 800
species

Found in Central and
South America
› Neotropical liana

Versatile plant
› Horticulture, food,
crafts, timber, dyes,
rituals, and
medicine
Arevalo, et al. 2011, Gentry and Cook 1984,
Gentry 1992, Witherup, et al. 1995

M. Obovata and M.
iquitosensis
› 2 most known
species
› 9 species total for
Martinella

M. iquitosensis known
to produce
martinelline and
martinellic acid

Chemically unique
› Natural
pyrroloquinoline ring
structures
› Synthesis is sought
after

Biologically unique
› Natural product
(not peptide) that
potently antagonize
bradykinin receptors
(GPCRs)
Pyrroloquinoline quinone
Davies, et al. 2013, Lovely and Mahmud 1999, , Ma, et al. 2001Ma, et al. 2003
Powell and Batey 2002, Shirai, et al. 2008, Yee, et al. 2006, Zhang, et al. 2007

Bark removal and
extraction

TLC and FCC
› Four fractions

IR spectra
Solvents Used
Extraction: CH2Cl2/MeOH
FCC: Hex/EtOAC gradient

1H and 13C NMR
› 2D more helpful…


This proved to be more of a learning
experience than productive
HPLC difficulties
› Long method time for little purified product
› Inconsistent results for first duplicate

Solubility tests
› H2O – no, EtOH (95%) – somewhat, DMSO
(99.5%) – yes

Disk diffusion antibiotic sensitivity testing
and MIC microtiter assays

Bacteria used
› Escherichia coli, Pseudomonas aeruginosa,
Bacillus cereus, and Staphylococcus aureus

Disk diffusion showed that only NB1-6-1,
NB1-6-6, and NB1-6-7 merited further
investigation

Clear results:
› EtOH (10.5%) + 1 mg/mL NB1-6-7 - S. aureus
› EtOH (5.25%) + .5 mg/mL NB1-6-7 - B. cereus
› DMSO (24.9%) + 1.5 mg/mL NB1-6-7 E. coli
› DMSO (24.9%) + 1.5 mg/mL NB1-6-7 S. aureus

Will run 2D NMRs overnight this week
2/3/14
› Hope to ID NB1-6-7
› Pyrroloquinoline ring in any sample?

If I had another semester
› Bradykinin receptor antagonism investigation
› LC-MS analysis to determine mass (no
preexisting method)

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(1) Arevalo, C.; Ruiz, I.; Piccinelli, A.; Campone, L.; Rastrelli, L. Phenolic derivatives from the leaves of
Martinella obovata (Bignoniaceae). Natural Product Communications, 2011, 6:7, 957-960.
(2) Gentry, A. H. A synopsis of Bignoniaceae ethnobotany and economic botany. Annals of the Missouri
Botanical Garden, 1992, 79, 53-64.
(3) Gentry, A.H.; Cook, K. Martinella (Bignoniaceae): A widely used eye medicine of South America.
Journal of Ethnopharmacology, 1984, 11, 337-343.
(4) Witherup, K.; Ransom, R.; Graham, A.; Bernard, A.; Salvatore, M.; Lumma, W.; Anderson, P.;
Pitzenberger, S.; Varga, S. Martinelline and martinellic acid, novel G-protein linked receptor
antagonists from the tropical plant Martinella iquitosensis (Bignoniaceae). Journal of the American
Chemical Society, 1995, 117, 6682-6685.
(5) Ma, D.; Xia, C.; Jiang, J.; Zhang, J. First Total Synthesis of Martinellic Acid, a Naturally Occurring
Bradykinin Receptor Antagonist. Organic Letters, 2001, 3:14, 2189-2191.
(6) Zhang, Z.; Zhang, Q.; Yan, Z.; Liu, Q. One-Step Synthesis of the Tricyclic Core of Martinellic Acid from
2-(Cyanomethyl)-3-oxo-N-arylbutanamides. Journal of Organic Chemistry, 2007, 72, 9808-9810.
(7) Ma, D.; Xia, C.; Jiang, J.; Zhang, J.; Tang, W. Aromatic Nucleophilic Substitution or CuI-Catalyzed
Coupling Route to Martinellic Acid. Journal of Organic Chemistry, 2003, 68, 442-451.
(8) Davies, S.; Fletcher, Ai.; Lee, J.; Lorkin, T.; Roberts, P.; Thomson, J. Asymmetric Synthesis of (-)Martinellic Acid. Organic Letters, 2013, 15:8, 2050-2053.
(9) Powell, D.; Batey, R. Total Synthesis of the Alkaloids Martinelline and Martinellic Acid via a Hetero
Diels-Alder Multicomponent Coupling Reaction. Organic Letters, 2002, 4:17, 2913-2916.
(10) Yee Ng, Pui.; Masse, C.; Shaw, J. Cycloaddition Reactions of Imines with 3-Thiosuccinic
Anhydrides: Synthesis of the Tricyclic Core of Martinellic Acid. Organic Letters, 2006, 8:18, 3999-4002.
(11) Shirai, A.; Miyata, O.; Tohnai, N.; Miyata, M.; Procter, D.; Sucunza, D.; Naito, T. Total Synthesis of (-)Martinellic Acid via Radical Addition-Cyclization-Elimination Reaction. Journal of Organic Chemistry,
2008, 73, 4464-4475.
(12) Lovely, C.; Mahmud, H. An approach to the pyrroloquinoline core of martinelline and martinellic
acid. Tetrahedron Letters, 1999, 40, 2079-2082.