Isolation of Martinella obovata via flash column chromatography
Naomi Bryner
Dr. David Singleton (advisor)Dr. Kathleen Halligan (advisor)
Plant Information
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
Overview
M. Obovata and M. iquitosensis› 2 most known
species› 9 species total for
Martinella M. iquitosensis
known to produce martinelline and martinellic acid
NH
N
HO
O
NH
NH
HN
HN
NH
Martinellic acid
NH
N
O
O
NH
NH
HN
HN
NH
HN
HN
NH
Martinelline
Martinelline & 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. 2003Powell and Batey 2002, Shirai, et al. 2008, Yee, et al. 2006, Zhang, et al. 2007
Summer 2013
Bark removal and extraction
TLC and FCC› Four fractions
IR spectra
1H and 13C NMR› 2D more helpful…
Solvents Used
Extraction: CH2Cl2/MeOH
FCC: Hex/EtOAC gradient
NB1-6-7 IR spectrum
NH
N
HO
O
NH
NH
HN
HN
NH
Martinellic acid
NH
N
O
O
NH
NH
HN
HN
NH
HN
HN
NH
Martinelline
Fall 2013 CHM (1 credit)
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
Fall 2013 BIO 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
Fall 2013 BIO
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
Loose ends
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)
References (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.
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