Semisynthesis and biological activity of stemofoline alkaloids.
The semisynthesis of the Stemona alkaloids (3'R)-stemofolenol (1), (3'S)-stemofolenol (2), methylstemofoline (3), and (3'S)-hydroxystemofoline (5) and the unnatural analogues (11E)-methylstemofoline (15) and 3'R-hydroxystemofoline (11) has been achieved starting from (11Z)-1',2'-didehydrostemofoline (4). This synthesis allowed, for the first time, access to diastereomerically enriched samples of 1 and 2 and the assignment of their absolute configurations at C-3'. These compounds were obtained in sufficient quantities to allow for their biological testing. In a quantitative assay as AChE inhibitors, (11Z)-1',2'-didehydrostemofoline (4) and (3'S)-hydroxystemofoline (5) were found to be the most active.
Baird
Morwenna C
MC
School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
Pyne
Stephen G
SG
Ung
Alison T
AT
Lie
Wilford
W
Sastraruji
Thanapat
T
Jatisatienr
Araya
A
Jatisatienr
Chaiwat
C
Dheeranupattana
Srisulak
S
Lowlam
Jaturong
J
Boonchalermkit
Sukanya
S
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D041901:Stemonaceae / Q000737:chemistry*; D013237:Stereoisomerism
C540538:(11Z)-1',2'-didehydrostemofoline; C540539:(3'S)-hydroxystemofoline; D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C481859:didehydrostemofoline; C430220:stemofoline