Solid-Supported Reagents in the Synthesis of Lamellarins and Deprotection of
Aromatic Ethers
Poonsakdi Ploypradith,* Kassrin Tangdenpaisal, Supannee Sualek, Rachel K. Kagan, Daniel R.
Bertoni, Vanessa Guzman, Somsak Ruchirawat
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, and Program in Chemical Biology,
Chulabhorn Graduate Institute, Vipavadee-Rangsit Highway, Bangkok 10210 Thailand.
E-mail: poonsakdi@cri.or.th
Recently, we have reported the applications
of solid-supported reagents in the synthesis of
lamellarins, a group of marine natural products
derived from sponges and ascidians. Three
solid-supported reagents were employed
successively in three reactions of keto alphabromination, base-mediated condensation to
assemble the pyrrole core, and acid-mediated
transacylation followed by lactonization.
Bromine on solid supports (Amberlyst A-26
Br3- and polymer bound pyridine hydrobromide
perbromide (PVPHP)) furnished the desired
phenacyl bromide carbonate derivatives in good
yields with remarkable selectivity (the ratio of
mono:di up to 35:1). Amberlyst A-26 NaCO3was effective for the condensation reactions of
benzyldihydro-isoquinoline with the derivatives
of phenacyl bromide or alpha-nitrocinnamate,
X
X
R 1O
O
R 1O
N
R 2O
R 3O
A m b e r ly s t A - 2 6 N a C O 3 R 5O
C O 2E t
R 6O
R 4O
O
Bn
A m b e r ly s t A - 2 6 N a C O 3
O
R 5O
Br
R 6O
NO2
O C O 2E t
R 4O
R O
C O 2E t
OBn
OR6
OR5
A m b e r ly s t- 1 5
R 1O
A m b e r ly s t A - 2 6 B r 3 - R 5 O
R 6O
O C O 2E t
M eO
CHO
or P V P HP
O
R 4O
OR6
OR5
R 4O
O
M eO
RO
O
OR6
OR5
A m b e r ly s t- 1 5
R 1O
M eO
X
Y
R = M e o r i- P r ; R 1 = i- P r ;
X = H , O B n , o r O i- P r ;
Y = H or O M e
O C O 2E t
OMe
R = M e o r i- P r
OR
O C O 2E t
Br
R 6O
i- P r O
RO
R = i- P r , tert- B u , a lly l,
Bn, P M B, M O M
2 ,3 - d im e th o x y b e n z y l,
2 ,3 ,4 - tr im e th o x y b e n z y l
O
N
O
R 5O
X
R 2O
R 3O
X
N
N
R 2O
R 3O
-
1
R 2O
R 3O
forming the pyrrole core. The Amberlyst-15mediated reactions of the 2H-pyrrole or the Obenzyloxy pyrrole completed the synthesis.
In addition, p-TsOH immobilized on either
silica (PTS-Si) or polystyrene (PS)—divinyl
benzene (DVB) polymer (Amberlyst-15) was
general and effective for the deprotection of
aromatic ethers. The i-Pr, tert-Bu, Bn, PMB,
allyl, MOM, di- and tri-methoxylated benzyl
protecting groups could be removed. When
these ethers were simultaneously present in the
same molecule but on different aromatic rings,
or even on the same aromatic ring, moderate to
excellent selectivity of their removal could be
obtained.
The corresponding carbocations
generated from these protecting groups were
proposed as important intermediates.
O
M eO
NO2
OMe
R 1O
OR2
R 1 = R 2 = B n , i- P r , a lly l, o r P M B
Ploypradith, P.; Cheryklin, P.; Niyomtham, N.; Bertoni, D. R.; Ruchirawat, S. Org. Lett. 2007, 9, 26372640.
Petchmanee, T.; Ploypradith, P.; Ruchirawat, S. J. Org. Chem. 2006, 71, 2892-2895.
Ploypradith, P.; Kagan, R. K.; Ruchirawat, S. J. Org. Chem. 2005, 70, 5119-5125.
Poonsakdi Ploypradith (พูนศักดิ์ พลอยประดิษฐ์ ), b 1971 in Bangkok, Thailand. The Johns
Hopkins University (BA 1994), The Johns Hopkins Univ. (PhD 1999, Prof. G. H.
Posner), Research Scientist, Chulabhorn Research Institute (2000-present), Lecturer,
Chulabhorn Graduate Institute (2007-present). Research field: total synthesis of natural
products and synthetic methodology.