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Synthese der Theonelladine A, B, C, D und von Niphatesin A
Author(s) -
Teubner Achim,
Gerlach Hans
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199319930129
Subject(s) - chemistry , hydrogenolysis , pyridine , medicinal chemistry , alkylation , methylamine , organic chemistry , yield (engineering) , alcohol , ethanol , ether , reagent , deoxygenation , catalysis , materials science , metallurgy
Syntheses of the Theonelladines A, B, C, D and of Niphatesine A The pyridine alkaloids theonelladine A–D ( 1 – 4 ) and niphatesine ( 5 ) of marine origin have been synthesized starting either from 3‐(4,4‐dibromo‐3‐butenyl)pyridine ( 6 ) or from 3‐pyridinecarbaldehyde. Reaction of 6 with two equivalents of BuLi gave the lithiated derivative of the alkyne 7 , which could be alkylated with 1‐bromo‐10‐(tetrahydro‐2‐pyranyloxy)decane ( 8 ) to yield the alkynol 9 after methanolysis. Selective hydrogenation of 9 with Lindlar palladium catalyst gave ( Z )‐14‐(3‐pyridyl)‐11‐tetradecan‐1‐ol ( 11 ). – Addition of the Grignard reagent of 12‐(benzyloxy)‐1‐bromododecane ( 13 ) to 3‐pyridinecarbaldehyde gave 17 , which was first oxidized (Swern) to give 18 and then reduced (Wolff‐Kishner) to give 14 . Hydrogenolysis of the benzyl ether 14 yielded 15 . The alcohol group in 9 , 11 , and 15 was converted into the tosyloxy group by reaction with tosyl chloride/pyridine. Subsequent reactions of the tosylates 10 , 12 , and 16 either with an excess of methylamine/ethanol or of ammonia/ethanol gave the pyridine alkaloids 1 – 5 in high yields as p ‐toluenesulfonates.