2
S. Bujaranipalli, S. Das / Tetrahedron Letters xxx (2016) xxx–xxx
OH
O
2,2-dimethoxypropane in the presence of a catalytic amount of
OH
O
O
PPTS to afford 24 in 87% yield. Compound 24 was then subjected
to Raney-Ni under hydrogen atmosphere for alkyne reduction as
well as benzyl deprotection in one pot to obtain compound 25.
The primary alcohol 25 was efficiently oxidized with IBX in
DMSO/THF at ambient temperature to provide the corresponding
aldehyde followed by the addition to a one-carbon ylide (generated
from CH3PPh+3Iꢀ, KtOBu in THF) led to olefin 26 in 76% yield. Desi-
lylation of 26 using TBAF in THF gave the desired alcohol fragment
14 in 89% yield.
Now the requisite acid fragment 13 was taken up and was pre-
pared from commercially available 2,4,6-trihyroxybenzoic acid
monohydrate 15 in five steps (Scheme 3). Treatment of compound
15 with trifluoroacetic acid (TFA), trifluoroacetic anhydride (TFAA),
and acetone provided the acetonide protected compound 27 in 60%
yield.18 Then, selective protection of the 4-hydroxyl group in 27
was achieved under the Mitsunobu conditions (PPh3 and DIAD)19
which was subsequently treated with trifluoromethanesulfonic
anhydride and pyridine in CH2Cl2 to furnish the corresponding tri-
flate 29 in 96% yield. Then, triflate 28 was subjected to the Stille
coupling20 with vinyltributyltin in the presence of LiCl to afford
30 in 88% yield. The isopropylidene protection was removed using
LiOHꢁH2O in THF/H2O (2:1) to afford the desired aromatic acid 13
in 87% yield.
O
O
O
H3CO
HO
OH
O
1
2
O
OH
OH
OH
O
O
O
R1O
R2
H3CO
OH
O
O
R4
R3
O
3
OH
OH
4: R1 = Me, R3 = H, R2 = R4 = OH
5: R1 = Me, R2 = R3 = H, R4 = OH
7: R1 = R2 = R4 = H, R3 = OH
OH
O
OH
O
O
O
R1O
R2
HO
R2
R1
O
R3
R3
8: R1 = R2 = R3 = H
11: R1 = Me, R2 = R3 = OH
6: R1,R3 OH, R2 =H
=
9: R1 + R2 = O, R3 =H
With both alcohols 13 and 14 in hand, we proceeded for the
construction of the macrocyclic framework (Scheme 4). The ester-
ification reaction between 13 and 14 was carried out under the
Mitsunobu reaction conditions to obtain the desired ester 12 in
84% yield. Then, ester 12 was treated with 10 mol% of the
Hoveyda–Grubbs second generation catalyst in degassed toluene
to provide the required lactone 31 in 86% yield and with exclusive
E-selectivity. Removal of the acetonide functionality in 31 was
achieved by treatment with 2 N HCl to furnish the target
molecule21 in 93% yield.
10: R1 = OH, R2 = R3 = H
Figure 1. Representative examples of resorcylic acid lactones.
which upon treatment with n-BuLi gave alkyne 16 in 82% yield.15
Regioselective opening of the epoxide 17 (prepared from racemic
propylene oxide which was resolved by using (R,R)-Salen-CoIIIOAc
catalyst16) was achieved with lithiated alkyne 16 to afford homo
propargyl alcohol 21 in 84% yield. The secondary alcohol present
in 21 was protected as its TBS ether using TBSCl/imidazole in
CH2Cl2 to furnish 22 in 94% yield. Then, compound 22 was treated
under the Sharpless asymmetric dihydroxylation conditions17
The spectral data (1H, 13C, MS and IR) of the synthesized target
compound were in good agreement with reported values of the
natural product 1 (see Supporting information for comparison
table), but when the specific rotation of synthetic 1 was compared
surprisingly, it was comparable with the specific rotation given to
using Ad-mix-
a to provide diol 23 in 82% yield with good diastere-
oselectivity (>97%, based on HPLC), which was then treated with
OH
OEt
OH
a
b
HO
c
BnO
OH
O
BnO
OH
O
18
BnO
20
O
19
O
O
OH
d
BnO
O
H3CO
16
21
O
OH
OH
O
OTBS
OTBS
OTBS
OTBS
OH
BnO
BnO
BnO
e
g
f
1
12
OH
23
22
O
O
OH
h
HO
O
24
OH
O
O
25
OH
O
+
OH
OH
OH
O
OTBS
O
OH
i
j
O
O
HO
O
O
O
14
15
13
26
14
Scheme 2. Reagents and conditions: (a) NaH, BnBr, THF, 0 °C–rt, 4 h, 80%, (b) (1)
(COCl)2, DMSO, TEA, CH2Cl2, ꢀ78 °C; (2) Ph3P = CHCO2Et, benzene, reflux, 4 h, 91%
from two steps; (c) (1) DIBAL-H, toluene, ꢀ78 °C, 30 min; (2) PPh3, CBr4, 0 °C, 1 h;
(3) n-BuLi, ꢀ78 °C, 1 h, 82% over three steps; (d) n-BuLi, BF3ꢁEt2O, 17, THF, ꢀ78 °C,
OH
O
HO
BnO
+
4 h, 84%; (e) TBSCl, imidazole, CH2Cl2, 0 °C–rt, 6 h, 94%; (f) AD-mix-a, MeSO2NH2, t-
18
16
17
BuOH/H2O, 0 °C, 24 h, 82%; (g) 2,2-DMP, PPTS (cat.), CH2Cl2, 0 °C–rt, 10 h, 87%; (h)
Raney-Ni, H2, EtOH, 12 h, 95%; (i) (1) IBX, DMSO/THF, rt; (2) CH3PPh+3Iꢀ, KtOBu, 0 °C–
rt, 2 h, 76% over two steps; (j) TBAF, THF, rt, 6 h, 89%.
Scheme 1. Retrosynthetic analysis of compound 1.