Post on 02-Nov-2014
Naming Alkaloids
Most compounds end in ……ine. Majority of alkaloids known by a trivial name.
• Colchicine Named after the common name of the organism.
NH
N
HN
O
NO
O
OH
HHO
ergotamine(Claviceps purpurea)
also known as the fungus, ergot
Species of organism
cocaine(Erythroxylum coca)
NCOOMe
OCOPh
Genus of organism
N
O
O
CH2OH
Ph
atropine(Atropa belladonna)Deadly nightshade
Physiological effect
N
MeN
MeO
MeO
OMe
OMe
H
H
H
emetine(Cephaelis ipecacuanha)
Ipecacuanhaemesis inducer
Mythology
O
HO
HO
N
morphine(Papaver somniferum)
Opium poppyname derived from Greek God morpheus
Researcher
N
NH
nicotine(Nicotiana tabacum)
named after the researcher Jaen Nicot
Animal Alkaloids
NCH2OH
O
H
(−)-castoramine(Castor fiberi)
Canadian beaver
N
(R)-(+)-muscopyridine(Moschus moschiferus)
Musk deer
NH OH
histrinocotoxin(Dendrobates histrionicus)
South American poison dart frogspiro piperidine
HN
OHH
H
O HH
samandarine(Salamandra maculosa)
European fire salamander
HN
N
Cl
epabitidine(Epipedobates tricolor)Ecuadorian poison frog
Insect Alkaloids
2,6-dialkylpiperidinesn = 10, 12, 14
Solenopsis invicta)Southern fire ant
precoccinelline
NH
(CH2)nCH3
N
H
H H
ON
H
H H
coccinelline
(Coccinella septempunctata)European 7-spotted ladybird beetle
N
N OMe
pyrazine
N
N
O
glomerineEuropean millipede
(Glomeris marginata)quinazolone
N
O
danaidone(Danaus chrysippus)
African Monarch butterflyphermone
epilachnene(Epilachna varivestis)Mexican bean beetle
azamacrolide
ONH
O
NH
O
O
NHO
O
(Subcoccinella 24-punctata)24-spotted ladybird
Marine Alkaloids
S SS
SSOMe
MeO
H2N
varacin(Polycitors sp.)
ascadian (sea squirt)
BrOMe
Br
BrN
O
convolutamine D(Amathia convoluta)
bryozoan (moss animal)
NH
NSO
BrNH2
Eudistomin L(Eudistoma gilboverde)
N NH
N
N
O
OH
H
OH
H
Manzamine F(Pellina sp.)
Okinawan sponge)
HN
OO
H2N
OH
CH2OHHO
OH
O
HHO
tetrodotoxin(Tetraodon sp.)
Japanese puffer fish(liver and ovaries)
Fungal Alkaloids
fusaric acid(Fusarium heterosporium)
mycotoxin
rugulovasine A(Penicillium concavo-rugulosum)
viridicatin(Penicillium viridactum)
2-quinolonechief mold on stored corn
N COOH
HN
OH
O
HN
NHCH3
O
O
sporidesmin A(Pithomyces chartarum.)
animal toxincauses pithomycotoxicosis
N
NNCl
MeOOMe
O
O
HOHO
H
SS
teleocidin B4(Streptomyces blastmyceticum)indole alkaloid tumor promotor
NH
NH
N
O
HOH
HN O
OO OH
HOH
H
cytochalasin b(Helminthosporia sp.)
NH O
OH
H
Me
Me
OHOH
H HMe
Me Me
(−)-penitrem D(Penicillium crustosum)tremogenic mycotoxin
roquefortine(Penicillium roquefortii)
blue cheese
NH
NNH
O
OHN
N
ergotamine
D-(+)-lysergic acid
NH
NMeH
HOOC
H
NH
NMeHH
HN
O
NO
NH
HO O
O
(Claviceps purpurea)sclerotium of fungus develops on the
ovary of rye, Secale cerale
Bacterial Alkaloids Very rare in nature.
procyanine(Pseudomonas aeroginosa)
deep blue colour
N
O
Alkaloid Extraction and Isolation General aspects Small amounts of alkaloid to isolate. Alkaloids must be free from impurities and artefacts. Crude material must be defatted (hexane, petroleum ether). Extract crude alkaloid from raw material into suitable solvent. Purify alkaloid by repeated conversion from base to salt and partitioning between organic and aqueous phases. Alkalis
• NH3/NH4OH • Ca(OH)2
Acids
• HCl, H2SO4, tartaric acid Solvents
• Benzene • Toluene • Chlorinated solvents (chloroform, dichloromethane) • Diethylether • Ethylacetate
Groups of Impurities to be Removed H2O/Ethanol soluble impurities
• proteins, saponins, gums, starches Organic solvent soluble impurities
• Lipids, fats, waxes, resins, pigments Organic Acids
• NH4OH Organic bases other than alkaloids
• Selective solubilities • Ion exchange resins • Preparative HPLC • Thick layer (preparative) TLC • Flash column chromatography
Extraction Methods Kian-Douglas method
• NH3/NH4OH Stats-Otto method
• HCl, H2SO4, tartaric acid Steam distilaltion
• nicotine pH gradient separation
• Vincristine, vinblastine (Catharanthus roseus)
Structural Elucidation Mass spectrometry
• FAB (Fast Atom Bombardment) • EI (Electron Impact) • MALDI-TOF (Matrix Assisted Laser Desorption/Ionisation –
Time of Flight) NMR (Nuclear Magnetic Resonance)
• 1-D: 1H, 13C, 15N • 2-D: HMQC, HMBC, TOCSY, NOE
Derivitisation Degradation studies IR, UV, elemental analysis X-ray crystallography Total synthesis Total synthesis – ultimate proof of structure
O
NH
ClO
HNO
N
O
N ClHN
OH2N
(−)-diazonamide A (proposed initial structure, 1991)
O NH
NH
ClO
HNO
N
O
N ClHN
OHO
(−)-diazonamide A (revised structure, 2001)
OH
HO
Harran P.G. et al, Angew. Chem. Int. Ed., 2001, 40, 4765-4773 Fenical W. et al, J. Am. Chem. Soc., 1991, 113, 2303-2304
(–)-Diazonamide A (toxin extracted from the marine invertebrate Diazona angulata). Total synthesis – ultimate proof of absolute configuration (–)-Quadrigemine C (representative of a higher order N-methyltryptamine derived plant alkaloid).
HN
MeN
H
HN
MeN
NMe
NH
H
H
NMe
NH H
absolute stereochemistry established as R (1999)
total synthesis (2002) ultimatelydetermined absolute stereochemistry of the vicinal quaternary carbons.Optical rotation, 1H, 13C-NMR, HRMS,HPLC properties identical to natural product.
Quadrigemine CPsychotria colorata
Amazonian plant used for treating paintetrapyrrolindoline alkaloid
Overman L.E. et al, J. Am. Chem. Soc., 2002, 124, 9008-9009