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RSC Advances
subsequent regioselective PMB ( p-methoxybenzyl) acetal cleavage
with DIBAL-H at 0 ꢀC in CH2Cl2 afforded 12 in 90% yield. Further,
the alcohol, on oxidation under Swern conditions, furnished an
aldehyde that aer aldol reaction with the chlorotitanium enolate
of N-propionyl thiazolidine-2-thione 13 at À40 ꢀC gave non-Evans
syn-aldol9 adduct 14 as a diastereomeric mixture (dr 95 : 5, deter-
mined by 1H NMR). The required major isomer 14 was easily
separated by silica gel column chromatography (Scheme 3).
The stereochemistry of 14 was conrmed by 13C NMR spec-
troscopic analysis.10 The resulting secondary alcohol was protected
as tert-butyldimethylsilylether11 to provide 15 (91%). Reductive
cleavage of the chiral auxiliary with DIBAL-H afforded aldehyde 16
followed by one-carbon Wittig homologation with triphenylphos-
phonium methylide produced terminal olen 17. Finally, DDQ-
mediated oxidative cleavage of the PMB (para-methoxybenzyl)
ether produced the targeted C9–C16 subunit 2 in 89% yield.
Thus, we have synthesized the C1–C8 and C9–C16 segments
2 and 3 of lyngbouilloside (1b), marine macrolide, with reas-
signed stereochemical and absolute conguration at C11, and
further investigations toward the total synthesis of lyngbouil-
loside (1b) are in progress.
Scheme 2 Reagents: (a) (i) (COCl)2, DMSO, Et3N, CH2Cl2, À78 ꢀC, 3 h;
(ii) S-BINOL, Ti(OiPr)4, allyltributyl tin, CH2Cl2, À78 ꢀC, 48 h, 90%; (b)
NaH, BnBr, TBAI, THF, 0 ꢀC-rt, 4 h, 93%; (c) (i) OsO4 (cat), NMO,
acetone–H2O (1 : 1), rt, 24 h; (ii) NaIO4, THF–H2O (2 : 1), 0 ꢀC, 30 min;
(iii) SnCl2, N2CHCOOEt, CH2Cl2, 0 ꢀC-rt, 3 h, 80% over 3 steps; (d)
PTSA, MeOH, 0 ꢀC, 2 h, 85%; (e) (i) IBX, EtOAc, reflux, 3 h. (ii)
Ph3P+CH3IÀ, n-BuLi, THF, À40 ꢀC-rt, 5 h, 60% over two steps.
Acknowledgements
TRR thank UGC, New Delhi for the award of a fellowship.
References
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Scheme 3 Reagents: (a) (i) OsO4 (cat), NMO, acetone–H2O (1 : 1), rt,
48 h; (ii) NaIO4, THF–H2O (2 : 1), 0 ꢀC, 30 min; (iii) NaBH4, MeOH, 0 ꢀC,
30 min, 89% over 3 steps; (b) NaH, BnBr, THF, 0 ꢀC-rt, 4 h, 92%; (c)
DIBAL-H, CH2Cl2, 0 ꢀC, 1 h, 90%; (d) (i) (COCl)2, DMSO, Et3N, CH2Cl2,
À78 ꢀC, 3 h; (ii) thione 13, TiCl4, DIPEA, CH2Cl2, À40 ꢀC, 4 h, 82%; (e)
TBSOTf, 2,6-lutidine, CH2Cl2, 0 ꢀC, 30 min, 91%; (f) DIBAL-H, CH2Cl2,
À78 ꢀC, 10 min; (g) Ph3P+CH3IÀ, n-BuLi, THF, À40–0 ꢀC, 5 h, 85% over
2 steps; (h) DDQ, CH2Cl2–H2O (9 : 1), 0 ꢀC, 30 min, 89%.
10 The stereochemistry of 14 was conrmed on the basis of 13
C
NMR spectra by converting 2 (derived from 14, Scheme 3)
into compound 18 through the following sequence of
reaction. In compound 2, TBS group was deprotected
followed by acetonide protection of 1,3-diol to give the cyclic
moiety 18. The appearance of distinctly different methyl
resonance peaks at d 19.1 and 30.3 ppm and the acetal
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