Communications
NaHCO3 to give the desired pyrroles 20 and 21, both in 70%
Keywords: alkaloids · cyclization · Michael addition ·
nitrostyrenes · total synthesis
.
yield (Scheme 6). The syntheses were completed by subject-
ing pyrroles 20 and 21 to hydrogenolysis to give compounds
22 and 23 quantitatively, followed by base-mediated lactoni-
zation with sodium hydride in dry THF to produce lamellar-
in K (1a) in 93% yield and lamellarin L (1b) in 87% yield
over two steps.
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Scheme 6. Synthesis of lamellarins K (1a) and L (1b). a) NaHCO3, 13,
CH3CN, reflux, 70% (20), 70% (21); b) H2, Pd/C, EtOAc; c) NaH,
THF, 93% (1a, over two steps), 87% (1b, over two steps).
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In summary, lamellarins K and L were successfully
synthesized in three steps from benzyldihydroisoquinolines
14 and 15 with ester nitrostyrene 13 in 65% and 61% overall
yields, respectively. The key step was the Michael addition/
ring-closure reaction which proceeded in 70% yield for both
lamellarins. The basic building blocks for the lamellarins are
the simple and easily prepared substituted-benzaldehyde
derivatives. Each lamellarin could be analyzed to consist of
three such building blocks, two in the benzyldihydroisoquino-
line derivative and the other in the ester nitrostyrene. Our
convergent synthetic approach offers a significant improve-
ment over others reported thus far in that it allows easy
incorporation of all aryl groups on the lamellarin skeleton
without the need for complex protecting-group strategies. The
benzyl group was chosen as the only necessary hydroxy-
protecting group since all of the benzyl groups could be
removed in the same step by simple palladium-catalyzed
hydrogenolysis. The syntheses of other lamellarins employing
this similar approach will be reported in due course.
Received: June 3, 2003
Revised: November 14, 2003 [Z52043]
868
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2004, 43, 866 –868