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L. Wang, W. Zhu / Tetrahedron Letters 54 (2013) 6729–6731
O
reduction of aldehyde with NaBH4 furnished alcohol 19 in 60%
O
OH
yield in three steps. The primary hydroxy group of 19 was acti-
vated using TsCl, and then replaced by LiAlH4 to give compound
21 in 71% yield in two steps. Deprotection of TIPS of 21 with TBAF
gave the erythro-11c. By interchanging protection between two
primary hydroxy groups, another erythro-isomer (11d) could be
prepared from compound 19. Thus, compound 19 was transformed
into erythro-11d in 39% yield after subjection to protection of pri-
mary hydroxy group with BnBr, deprotection of TIPS with TBAF,
activation of a newly formed primary hydroxy group by TsCl fol-
lowed by replacement with LiAlH4, and debenzylation with H2/
Pd–C (Scheme 3).
OH
9
O
O
O
O
O
O
OH
CHO
11
10
Scheme 1. Retro-synthetic analysis of versicolactones A and B.
HO
OH
O
O
O
i-iv
i-iv
2-Buten-4-lactone (9) was converted into lithiated butenolide
by freshly prepared LDA at –78 °C in THF, and then was treated
with freshly prepared 10a by Swern oxidation of 11a9 at –78 °C
to give 26 in 27% yield of two steps. Dehydration of butenolide
MeO2C
CO2Me
OH
OH
12
13
11a
HO
OH
O
13
26 with Ac2O–Et3N–DMAP in dry CH2Cl2 gave 27a and 27b in
MeO2C
CO2Me
11b
46% and 48% yields, respectively. The configuration of the double
bond in the side chain of 27a and 27b was confirmed by NOESY
correlations between H-3 with H-5 and H-6 (Figs. S47 and S50),
respectively. Deprotection of isopropylidene of 27a and 27b with
TFA in MeCN–H2O afforded 1 and 2 in 62% and 68% yields, respec-
tively (Scheme 4). By the same procedures, compounds 3 and 4, 5
and 6, and 7 and 8 were synthesized from 11b, 11c, and 11d,
respectively.
Scheme 2. Synthesis of threo-11a and 11b. Reagents and conditions: (i) DMP, PTSA,
CH2Cl2, reflux; (ii) NaBH4, MeOH; (iii) TsCl, (n-Bu)4NHSO4; (iv) LiAlH4/THF.
mediates (11c and 11d) need to undergo chiral separation if they
were prepared from the meso-dimethyl tartrate. Another selectable
method to synthesize 11c and 11d is from D-lyxose and D-ribose
The 1H and 13C NMR data of compounds 1 and 2 (Table 1) were
not consistent with the natural versicolactones A and B, especially
the chemical shifts of C-5 and C-8. In contrast, NMR (Table 1,
Figs. S85 and S86) and specific rotation data of the synthetic 5
but need to use the foul ethanethiol.10 To avoid expensive chiral
separation and the foul ethanethiol, we use a chiral pool of ery-
L-rhamnose to synthesize erythro-11c and 11d
through protection, oxidation, and reduction steps (Scheme 3).
thro-2,3-diol in
(½
a
ꢀ
D –33.8) and 6 (½
a D +20.5) were found to be identical with those
ꢀ
Compound 16 was synthesized in 70% yield from L-rhamnose
published for versicolactones A (½a D25
ꢀ
–31.5) and B (½a D
ꢀ
+19.8).3
through protection of erythro-vicinal diol11 followed by NaBH4
reduction.12 The primary hydroxy group of 16 was protected by
TIPSCl, and then oxidative cleavage of vicinal diol followed by
Therefore, the structure of natural products, versicolactones A
and B should be revised as 5 and 6, respectively.
OH OH
O
O
O
OH
OH
OH OTIPS
iv. 76% yield
v. 92% yield
O
17
O
O
vi. 90% yield
vii. 79% yield
iii
i, ii
HO
O
HO
O
HO
70% yield
85% yield
OTIPS
19
O
TIPSO
O
OH
14
OH
21
16
ix. 78% yield
x. 90% yield
viii
86% yield
O
xi. 94% yield
xii. 70% yield
xiii. 84% yield
O
O
O
O
O
O
OH
HO
OBn
OH
OBn
11d
25
11c
23
Scheme 3. Synthesis of erythro-11c and 11d. Reagents and conditions: (i) p-TsOH/DMP, acetone, rt, 2 h; (ii) NaBH4, H2O, 0 °C to rt, 2 h; (iii) TIPSCl, imidazole, DMAP, CH2Cl2,
0 °C to rt, 6 h; (iv) NalO4, AcOH, H2O/EtOH, pH 5, 5 °C to rt, 1 h; (v) NaBH4, H2O/THF, 0 °C to rt, 2 h; (vi) TsCl, DMAP, Et3N, CH2Cl2, 0 °C to rt, 6 h; (vii) LiAlH4, THF, 65 °C, 5 h;
(viii) TBAF, THF, 0–10 °C, 20 min; (ix) BnBr, NaH, DMF, 0 °C to rt, overnight; (x) TBAF, THF, 0–10 °C, 20 min; (xi) TsCl, DMAP, Et3N, CH2Cl2, 0 °C to rt, 6 h; (xii) LiAlH4, THF, 65 °C,
5 h; (xiii) H2/Pd/C, EtOAc/MeOH, rt, overnight.
OH
O
O
OH
O
O
iv
O
O
O
O
O
O
O
i
O
O
9
O
iii
1
O
27a
O
ii
OH
CHO
O
iv
OH
OH
OH
10a
11a
26
O
O
O
O
O
27b
2
Scheme 4. Synthesis of 1 and 2. Reagents and conditions: (i) (COCl)2, DMSO, Et3N, CH2Cl2, ꢁ78 °C; (ii) LDA, THF, ꢁ78 °C, 1.5 h; (iii) Ac2O, Et3N, DMAP, CH2Cl2, rt, 2 h; (iv) TFA,
MeCN/H2O 2:1, 0 °C to rt, 2 h.