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lactone alcohols 5a and 5b, thereby making our route as
protection free method (Scheme 4). Chelation of metal–enolate
with oxygen bearing a negative charge of the C-4 hydroxymethyl
group might control the high diastereoselectivity of this alkyl-
ation step.
Notes and references
1 (a) R. S. Ward, Nat. Prod. Rep., 1999, 16, 75–96; (b) M. Saleem,
H. J. Kim, M. S. Ali and Y. S. Lee, Nat. Prod. Rep., 2005, 22,
696–716; (c) S. Hanessian and G. J. Reddy, Synlett, 2007, 3,
475–479; (d) J.-Y. Pan, S.-L. Chen, M.-H. Yang, J. Wu,
J. Sinkkonen and K. Zou, Nat. Prod. Rep., 2009, 26, 1251–
1296, and references therein.
2 T. Akindele, S. P. Marsden and J. G. Cumming, Org. Lett.,
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3 D. Takaoka, K. Watanabe and M. Hiroi, Bull. Chem. Soc. Jpn.,
1976, 49, 3564–3566.
4 Y. L. Huang, C. C. Chen, F. L. Hsu and C. F. Chen, J. Nat.
Prod., 1996, 59, 520–521.
5 C. C. Chang, Y. C. Lien, K. C. S. Chen Liu and S. S. Lee,
Phytochemistry, 2003, 63, 825–833.
6 Racemic synthesis: (a) U. Jahn and D. Rudakov, Org. Lett.,
2006, 8, 4481–4484; (b) R. Stevenson and J. R. Williams,
Tetrahedron, 1977, 33, 285–288.
7 Asymmetric synthesis: (a) C. E. Rye and D. Barker, J. Org.
Chem., 2011, 76, 6636–6648; (b) H. Kim, C. M. Wooten,
Y. Park and J. Hong, Org. Lett., 2007, 9, 3965–3968; (c)
K. Matcha and S. Ghosh, Tetrahedron Lett., 2008, 49, 3433–
3436; (d) P. Xue, L.-P. Wang, X.-Z. Jiao, Y.-J. Jiang, Q. Xiao,
Z.-G. Luo, P. Xie and X.-T. Liang, J. Asian Nat. Prod. Res.,
2009, 11, 281–287; (e) T. Esumi, D. Hoyjo, H. Zhai and
T. Fukuyama, Tetrahedron Lett., 2006, 47, 3979–3983, and
references therein.
8 (a) S. Hajra, A. K. Giri, A. Karmakar and S. Khatua, Chem.
Commun., 2007, 2408–2410; (b) S. Hajra and A. K. Giri,
J. Org. Chem., 2008, 73, 3935–3937; (c) S. Hajra,
A. K. Giri, A. Karmakar and S. Hazra, Tetrahedron Lett.,
2008, 49, 3625–3627; (d) S. Hajra, A. K. Giri and S. Hazra,
J. Org. Chem., 2009, 74, 7978–7981; (e) S. Hajra,
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Compounds 12 via the intermediacy of corresponding
bromo-compounds 13a and 13b were converted to 3,4-dimethyl
lactones 6a and 6b by NaCNBH3 reduction in 83% yields over
two steps. Methyl acetals 14a and 14b were prepared7b in one
pot from 6a and 6b by DIBAL-H reduction at ꢁ78 ꢀC, quenching
with MeOH and then reacting with trimethylorthoacetate in
presence of catalytic amount of PTSA at room temperature.
Finally BF3–Et2O mediated Friedel–Cra reaction7b of 14a with
3,4-dimethoxybenzene and 14b with 3,4-methylenediox-
ybenzene at low temperature (2 h at ꢁ78 ꢀC then 10 h at ꢁ20 ꢀC)
completed the synthesis of (+)-galbelgin 1 {[a]2D8 ¼ +80.0 (c 0.5,
CHCl3), lit.7b [a]D28 ¼ +80.7 (c 0.55, CHCl3), lit.1c [a]2D8 ¼ +83.4
(c 0.47, CHCl3)}, and (+)-galbacin 2 {[a]2D8 ¼ +110 (c 1.0, CHCl3),
lit.3 [a]2D8 ¼ +117 (CHCl3)} in 39% and 36% overall yields in seven
steps from N-succinyl-2-oxazolidinone 8 (Scheme 4). Spectral
data of synthesized 1 and 2 were in good agreement with liter-
ature reports.1c,3,7b Unlike other literature reports,7b,d no epime-
rization was observed during the Friedel–Cra reaction of
methyl acetals 14a,b. Interestingly, this route could provide
recently isolated hybrid THF-lignans having 90-OH/OMe and
9-deoxy units (R1 ¼ H, R2 ¼ OH, OMe).10
In conclusion, a notably brief and diastereoselective tactic
has been reported for the synthesis of all trans- variant of 2,5-
diaryl-3,4-disubstituted tetrahydrofuran lignans from readily
available reagents. The sequence utilizes boron-mediated syn-
aldol reaction, which diastereoselectively adds the N-succinyl
oxazolidinone to electron rich aromatic aldehydes. The chirality
generated in this reaction guides the formation of four
consecutive stereocenters found in target compounds 1 and 2.
The protection free total synthesis of (+)-galbelgin and (+)-gal-
bacin has been completed with overall yields of 39% and 36%,
respectively. This is the rst asymmetric synthesis of
(+)-galbacin.
9 R. O. Hutchins, B. E. Maryanoff and C. Milewski, J. Chem.
Soc. D, 1971, 1097–1098.
10 (a) L. G. Felippe, D. C. Baldoqui, M. J. Kato, V. Da-S. Bolzani,
E. F. Guimaraes, R. M. B. Cicarelli and M. Furlan,
Phytochemistry, 2008, 69, 445–450; (b) C. J. Ma, Y. C. Kim
and S. H. Sung, J. Enzyme Inhib. Med. Chem., 2009, 24,
1117–1121.
Acknowledgements
CSIR, New Delhi is gratefully acknowledged for nancial
support. S. Hazra thanks UGC, New Delhi for his fellowship.
22836 | RSC Adv., 2013, 3, 22834–22836
This journal is ª The Royal Society of Chemistry 2013