Lycoposerramine-S
Angew. Chem. Int. Ed.
2012, 51, 11824
TN. Shimada, Y. Abe, S. Yokoshima, T. Fukuyama*
The retrosyntheses of Lycoposerramine S beings with the
deprotection of the Boc group, N-methylation
(para-formaldehyde and sodium cyanoborohydride) and deprotection of the nosyl
(4-nitrobenzenesulfonamide) group from 13. Compound 13
was prepared from 12 by bis-mesylating the bis-alcohol and then treating it with 4-nitrobenzulfonamide using
Cs2CO3 as the base.
This is the first time I saw the use of 4-nitrobenzenesulfonamide to
install the nosyl group. Compound 12 was prepared from hydroxyalkene 11 by first activating the hydroxyl
group as thionocarbonate and then cyclizing it under free-radical-conditions to
the alkene group. Alkene 11 was prepared by dehydrating the
secondary alcohol in 10. Compound 10
was prepared by the reduction of the ketone group and reductive removal of the
chiral auxiliary in compound 9,
which in turn, was prepared by reacting aldehyde 7 with amine 8. The reaction between 7 and 8 is the key step
of this synthesis. Aldehyde group reacts
with the amine to generate the amine which then gets polarized and undergoes a
1,3-dipolar addition with the alkene group thereby completing the bicyclic-ring
formation as shown in the graphic below the main scheme. Aldehyde 7
was prepared by oxidation of alcohol 6,
which in turn was derived from vinyl-iodide 4 by going through an initial metal-halogen exchange followed by
addition of lactone 5. Vinyl-iodide 4 was prepared from symmetrical alkyne 3, which was easily obtained from alkyne 1.
Overall, this is a very interesting synthesis from the
Fukuyama group in the sense that the product is formed from rather simple
looking precursors and is made with the minimum of fuss. The cycloaddition step is quite noteworthy.
