Total synthesis of (+)-fostriecin and (+)-phoslactomycin B

Article abstract of DOI:10.1055/s-0029-1216930

(+)-Fostriecin and (+)-phoslactomycin B, which are potent and selective inhibitors of protein phosphatase, were synthesized by a highly enantio-and stereoselective approach that enabled us to prepare all possible isomers at both the C11 secondary alcohol position and the δ¹²-double bond. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216930

PAPER
2935
Total Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B
(
+)-Fostriecin
e
and(+)-P
h
t
s
ycinB uya Shibahara, Masataka Fujino, Yasumasa Tashiro, Nanako Okamoto, Tomoyuki Esumi, Keisuske Takahashi,
Jun Ishihara, Susumi Hatakeyama*
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
Fax +81(95)8192426; E-mail: susumi@nagasaki-u.ac.jp
Received 29 May 2009
flexible. We expected that the advanced intermediate 3, as
well as its stereoisomers 4, 5, and 6, would each be avail-
able from 7 by a combination of stereoselective formation
of the (E)- or (Z)-iodoenone14 and C9-OH directed anti- or
syn-selective reduction.15 To access 7, we envisaged an
Abstract: (+)-Fostriecin and (+)-phoslactomycin B, which are po-
tent and selective inhibitors of protein phosphatase, were synthe-
sized by a highly enantio- and stereoselective approach that enabled
us to prepare all possible isomers at both the C11 secondary alcohol
position and the D12-double bond.
approach from alcohol
8
involving ring-closing
Key words: antibiotics, fostriecin, phoslactomycin, total synthesis
metathesis16 and Sharpless asymmetric dihydroxylation,17
both of which were thought to be challenging in terms of
selectivity because of the possibility of reaction occurring
at several sites. In addition, the key issues to be addressed
for the synthesis of 2 were stereoselective construction of
the C4 asymmetric center and the installation of the C8
asymmetric quaternary center along with its aminoethyl
substituent.
The soil bacteria species Streptomyces produce a series of
structurally novel antifungal and antitumor antibiotics
that include fostriecin,1 PD113,271,1 the phoslactomycins
A–F and I,2 the phosphazomycins C1 and C2,3 and the
leustroducsins A–C and H.2e,4 These compounds are high-
ly potent and selective inhibitors of protein serine/threo-
nine phosphatase 2A, which may account for their
antitumor activity.5,6 Because of their intriguing molecu-
lar architectures and their potential as a lead compounds
for anticancer drugs, as well as their importance as biolog-
ical tools, this class of compounds has attracted much at-
tention in the chemical and biological communities.7 As a
result, there have been a number of formal and total syn-
theses of fostriecin,5a,8,9 PD113,271,10 leustroducsin
B,11,12 and phoslactomycin A and B,13 including ours.
Here, we describe details of our total syntheses of (+)-fos-
triecin (1)9f and (+)-phoslactomycin B (2);13c the methods
used also enabled us to prepare various analogues of these
compounds.
R1
OH OP
*
X
fostriecin (1)
or
PLM-B (2)
4
• phosphorylation
• Stille coupling
8
9
11
O
O
Y
R2
OP
3: 11R, X = I, Y = H
4: 11R, X = H, Y = I
5: 11S, X = I, Y = H
6: 11S, X = H, Y = I
asymmetric
dihydroxylation
RCM
R1
R1
OP
OP
O
OP
O
O
HO
R2
R2
7
8
for 1: R1 = H, R2 = Me
for 2: R1 = Et, R2 = CH2CH2NHP
The close structural similarity between (+)-fostriecin (1)
and (+)-phoslactomycin B (2) allowed us to devise a com-
mon synthetic plan, which is illustrated in Scheme 1. We
envisaged ynone 7 as a precursor to make our approach
Scheme 1 Retrosynthetic analysis of fostriecin and phoslactomycin
B
The synthesis of fostriecin (1) began with the stereoselec-
tive preparation of trienol 12 (Scheme 2). 2,3-Dihydrofu-
ran was first converted into the (3E)-4-
(tributylstannyl)pent-3-en-1-ol with complete E-selectivi-
ty by means of Aldisson’s procedure.18 (3E)-4-(Tributyl-
stannyl)pent-3-en-1-ol was subjected to p-methoxy-
benzylation to give the ether 9, which was iodinated to
give alkenyl iodide 10. Heck reaction19 of the iodide 10
with acrolein, gave the aldehyde 11. Brown’s asymmetric
allylation20 of 11 gave alcohol 12 in good yield. The opti-
cal purity of 12 was not determined at this stage because
of its instability both under the conditions for HPLC anal-
ysis on a chiral column and for formation of the corre-
sponding 2-methoxy-2-(trifluoromethyl)(phenyl)acetate
(MTPA) esters.
HO
O
R
P
O
OH
HO
OH
R = H: fostriecin (1)
O
O
= OH: PD113,271
OH
HO
HO
O
O
4
P
OH
R = H: phoslactomycin B (2)
(PLM-B)
= OCOR': phoslactomycins
phosphazomycins
leustroducsins
8
O
O
OH
R
H2N
Figure 1 Related phosphate esters produced by Streptomyces spe-
cies
SYNTHESIS 2009, No. 17, pp 2935–2953
Advanced online publication: 07.08.2009
x
x.
x
x
.
2
0
0
9
DOI: 10.1055/s-0029-1216930; Art ID: C01809SS
© Georg Thieme Verlag Stuttgart · New York

2936
S. Shibahara et al.
PAPER
OH
Table 1 Ring-Closing Metathesis of Acrylate 13
Bu3Sn
PMBCl
t-BuLi, THF, –60 to 0 °C
Yield (%)b
O
then (Bu3Sn)2Cu(CN)Li2
–30 to –10 °C
then MeI, –40 °C to r.t.
NaH, Bu4NI, DMSO
8
Entry
Solventa
CH2Cl2
CH2Cl2
Temp (°C) Time (h) 14
15
7
83%
90%
1
2
3
4
5
6
r.t.
r.t.
40
80
r.t.
r.t.
24
24
20
23
24
24
60
53
75
25
17
31
OPMB
OPMB
CH2=CHCHO
Pd(OAc)2 (2 mol%)
I2
Bu3Sn
I
8
CH2Cl2, 0 °C
K2CO3, Bu4NCl
DMF
c
9
10
CH2Cl2
4
100%
73%
EtOAc
THF
13
10
19
(+)-Ipc2BOMe
H2C=CHCH2MgBr
Et2O-toluene, –78 °C
OPMB
OPMB
OHC
then 30% H2O2
3 M NaOH, THF
HO
toluene
11
12
a All reactions were carried out in 10 mM soln.
b Isolated yields.
81%
Scheme 2 Preparation of alcohol 12
c Ti(O-i-Pr)4 (0.3 equiv) was added.
After acryloylation of alcohol 12, the key ring-closing
metathesis of acrylate 13 in the presence of the first-gen-
eration Grubbs catalyst was examined under various con-
ditions (Scheme 3 and Table 1). Dichloromethane was
identified as the solvent of choice, and the cyclization
took place selectively between the two terminal olefinic
double bonds. When the reaction was conducted under the
conditions shown in entry 3, the desired dihydropyranone
14 was obtained in 75% yield, along with the dimer 15
(4% yield). Dimer 15 was the only byproduct that was iso-
lated in all the reactions, and the conjugated diene moiety
did not react at all. Addition of titanium
tetraisopropoxide21 did not improve the yield of 14 (entry
2). The optical purity of 14 was determined to be 77% ee
by HPLC using a chiral column, confirming the enantio-
selectivity of the asymmetric allylation leading to 12.
14 with 77% ee, suggesting that the dihydroxylation reac-
tion was accompanied by kinetic resolution. To elaborate
the C11–C13 moiety, diol 16 was converted into ynone 21
in 84% overall yield by a five-step sequence involving si-
lylation, oxidative removal of the p-methoxybenzyl
group, Dess–Martin oxidation, addition of acetylene, and
a second Dess–Martin oxidation.
To apply Kishi’s methodology,14 the addition of hydrogen
iodide to ynone 21 was then examined under various con-
ditions (Table 2). When 21 was exposed to 1.1 equiva-
lents of sodium iodide and 4.4 equivalents of acetic acid
in the absence of an added solvent at room temperature,
the kinetically formed (Z)-isomer 22 isomerized into the
thermodynamically more stable (E)-isomer 23 to an ap-
preciable extent (Z/E = 76:24; entry 1) even after only 30
min; after 3 h, pure (E)-23 was obtained in 81% yield (en-
try 2). After we had experimented with various conditions
in which a solvent was used to retard the isomerization,
we eventually found that acetone was the solvent of
choice for the predominant production of the (Z)-isomer
22. Thus, on treatment of 21 with 2 equivalents of sodium
PMBO
PMBO
H2C=CHC(O)Cl
HO
Et3N, CH2Cl2, 0 °C
80%
O
O
13
12
Table 2 Addition of Hydrogen Iodide to Ynone 21
TESO
O
TESO
O
X
PCy3
Ru
Ph
Cl
Cl
O
O
O
O
Y
OTES
OTES
PCy3
OPMB
PMBO
21
22: X = I, Y = H
23: X = H, Y = I
(10 mol%)
Table 1
+
O
O
O
O
Reagent (equiv)a
Entry NaI AcOH Solvent
Yield (%)b
14
(77% ee)
dimer 15
Time (h) 22
23
10
81
17
1
21
25
0
Scheme 3 Preparation of lactone 3
1
2
3
4
5
1.1
1.1
1.1
2
4.4
4.4
4.4
1.1
1.1
none
0.5
3
31
0
To introduce the (8R,9R)-diol functionality, 14 was ex-
posed to Sharpless asymmetric dihydroxylation condi-
tions using AD-mix-b (Scheme 4). As
dihydroxylation took place at the most electron-rich and
the sterically least-hindered olefin with complete regio-
and diastereoselectivity to give diol 16 in good yield.22 In-
terestingly, enantiomerically pure 16 was obtained from
none
acetone
acetone
acetone
14
53
62
63
11
23
0
a result,
48
72
2
6
a All reactions were carried out at r.t.
b Isolated yield.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2937
AD-mix-
MeSO2NH2
β
to produce the (Z)-triene 31 as the sole product in a satis-
factory yield. As we reported previously,9f we successful-
ly improved the final phosphorylation–deprotection step
by the use of a diallyl phosphate group. Thus, reaction of
31 with diallyl diisopropylaminophosphine27 followed by
treatment of the resulting phosphite with tert-butyl hydro-
peroxide gave phosphate 32. Finally, palladium-catalyzed
reductive deallylation28 followed by desilylation using hy-
drogen fluoride/pyridine gave (+)-fostriecin (1) cleanly.
The synthetic substance was identical in every respect to
natural fostriecin. Note that possible side reactions, such
as cleavage of the lactone via a p-allyl palladium complex
or isomerization of the triene system, did not occur under
palladium-catalyzed deallylation conditions.
OPMB
OH OPMB
O
O
O
O
t-BuOH–H2O
0 °C
OH
80%
16
14
(100% ee)
(77% ee)
TESOTf
2,6-lutidine
TESO
OPMB
17: R = PMB
18: R = OH
DDQ, 0 °C
CH2Cl2/H2O
O
O
CH2Cl2
–78 °C
OTES
91%
99%
DMP
CH2Cl2, 0 °C
TESO
HC≡CMgBr, CeCl3
CHO
O
O
100%
THF, –50 °C
98%
OTES
19
TESO
X
20: X = H(OH)
21: X = O
DMP
CH2Cl2, 0 °C
O
O
OTES
SnBu3
95%
OTBDPS
OH OTBS
Scheme 4 Preparation of ynone 21
OH OR
30
O
O
88%
OTES
OTES
iodide and 1.1 equivalents of acetic acid in acetone at
room temperature for 2 days, 22 and 23 were obtained in
62% and 1% yields, respectively, together with unreacted
21 (23% yield; entry 4); the yield of the (Z)-isomer 22 cor-
responds to 81% based on recovered 21.
I
OTBDPS
25: R = H
TBSOTf
2,6-lutidine, CH2Cl2, –78 °C
31
29: R = TBS
81%
O
P
O
(H2C=CHCH2O)2PN(i-Pr)2
tetrazole, CH2Cl2, 0 °C
O
O
OTBS
From (Z)-isomer 22, either an (11R)- or an (11S)-stereo-
center was established selectively by two methods via the
deprotected alcohol 24 (Scheme 5).
then t-BuO2H, 0 °C
89%
O
O
OTES
32
OTBDPS
1) Pd(PPh3)4 (10 mol%)
HCO2NH4, Ph3P, THF
then Dowex-50, MeOH
Me4NBH(OAc)3
AcOH, MeCN
I
OR
O
OH OH
I
–30 °C
(+)-fostriecin (1)
2) HF-pyridine-H2O-MeCN
then NaHCO3
99%
O
O
O
O
OTES
OTES
79%
22: R = TES
24: X = H
25 (84% de)
HF-pyridine
aq MeCN
0 °C
81%
Scheme 6 Completion of the total synthesis of fostriecin
NaBH4, Et3B
THF–MeOH (6:1)
–78 °C
OH OH
OTES
I
For the preparation of alcohol 8, a key precursor of phos-
lactomycin B, as shown in Scheme 1, we envisaged an
approach from alcohol 33 involving Suzuki–Miyaura
coupling29 and asymmetric pentenylation. We expected
that the reaction of 33 with a chiral (2Z)-pent-2-en-1-yl-
borane or -boronate would proceed in the same fashion as
Brown’s or Roush’s asymmetric crotylation,30,31 allowing
us to assemble the C4 and C5 stereogenic centers with the
desired diastereo- and enantioselectivity, although such
asymmetric pentenylation was unprecedented.32
24
90%
O
O
26 (exclusive)
OH OH
*
11
27: 11R (78%, 2 steps)
28: 11S (79%, 2 steps)
23
O
O
I
OTES
Scheme 5 Preparation of pivotal intermediates
After selective desilylation of 22, Evans’s anti-selective
reduction23 of 24 by sodium triacetoxyborohydride result-
ed in the formation of the (11R)-diol 25 with 84% de in
excellent yield. On the other hand, sodium borohydride
reduction using triethylborane24 converted 24 into the
(11S)-diol 26 with complete selectivity in good yield.
Similarly, from the (E)-isomer 23, the corresponding
(11R)-diol 27 and (11S)-diol 28 were obtained, again with
excellent selectivity.
asymmetric
pentenylation
4
PMBO
OHC
5
PLM-B (2)
HO
OP
I
PHN
33
Suzuki–Miyaura
coupling
8
Scheme 7 Synthetic plan for the preparation of key intermediate 8
Having developed a methodology for preparing diol 25
and all its isomers at the C11 stereocenter and the D12-
double bond, we then investigated the conversion of 25
into fostriecin (1). Selective silylation of 25 afforded
Jacobsen’s intermediate 29,9c which was then subjected to
palladium-catalyzed Stille coupling25 with stannane 3026
The required aldehyde 33 was prepared stereoselectively
from propane-1,3-diol, as shown in Scheme 8. Thus, pro-
pane-1,3-diol was first converted into iodoalkene 34 as a
4:1 Z/E mixture by p-methoxybenzylation, Swern oxida-
tion, and Horner–Emmons reaction with ethyl (diethoxy-
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2938
S. Shibahara et al.
PAPER
phosphoryl)iodoacetate generated in situ.33 Reduction of
34 with diisobutylaluminum hydride (DIBAL-H), fol-
lowed by oxidation with 2,2,6,6-tetramethylpiperidine-1-
oxyl (TEMPO) gave the (Z)-aldehyde 35 with a high geo-
metric purity (20:1), so that the moderate Z/E-selectivity
of the iodoalkenylation step did not become a serious
problem. Interestingly, Dess–Martin and Swern oxidation
conditions did not promote this isomerization effectively.
Wittig reaction of 35 with ethyl (triphenylphosphor-
anylidene)acetate gave the ester 36 stereoselectively; this
was then subjected to DIBAL-H reduction and Swern ox-
idation to give aldehyde 33 in good yield.
Table 3 Asymmetric Pentenylation of 33
OPMB
OPMB
OHC
HO
I
I
38
33
Entry
Methoda
Yield (%)b syn/antic,d ee (%) (config.)e
1
2
3
A
B
C
98
82
79
25:75
100:0
100:0
not determined
93 (S)
46 (S)
a Method A: (2Z)-1-bromopent-2-ene, Mg, Et2O, –20 °C, then
(+)-(Ipc)2BOMe, –78 °C to r.t., then 33, toluene, –78 °C; Method B:
(2Z)-pent-2-ene, t-BuOK, BuLi, THF, –78 °C, then (+)-(Ipc)2BOMe,
BF3·Et2O, 33, THF, –78 to –50 °C; Method C: (2Z)-pent-2-ene,
t-BuOK, BuLi, THF, –78 °C, then B(O-i-Pr)3, then 1 M HCl, diiso-
propyl D-tartrate, then 33, toluene, –78 °C.
1) PMBCl
KOH, DMSO
2) Swern oxidation
1) DIBAL-H
CH2Cl2, –78 °C
PMBO
EtO2C
HO
OH 3) (EtO)2P(O)CH2CO2Et
NaH, I2, THF
2) TEMPO
PhI(OAc)2
CH2Cl2
I
34
Z:E = 4:1
62%
79%
b Isolated yield.
c Determined by 1H NMR analysis of the product.
d Determined by NOE analysis of 38 and its C4-epimer.
e Determined by 1H NMR analysis of the corresponding (R)- and (S)-
MTPA esters, as well as by HPLC analysis of 38 using a chiral col-
umn.
PMBO
PMBO
DIBAL-H
CH2Cl2, –78 °C
Ph3P=CHCO2Et
OHC
EtO2C
98%
THF
100%
I
I
36
35
Z:E = 20:1
X
OPMB
methane to give unsaturated lactone 41 cleanly. In this
particular case, the first-generation Grubbs catalyst did
not induce efficient cyclization.
37: X = H(OH)
33: X = O
Swern oxidation
84%
H
I
Scheme 8 Preparation of aldehyde 33
To introduce the (8R,9R)-diol functionality, lactone 41
was subjected to dihydroxylation conditions using AD-
mix-b, as established in the synthesis of fostriecin (1);
however, these conditions turned out to be unsatisfactory
in terms of reproducibility. After exploring various condi-
tions, we eventually found that reaction of 41 with Super-
AD-mix,35 using the ligand for Sharpless asymmetric di-
hydroxylation [(DHQD)2PHAL] as a chiral ligand, result-
ed in highly diastereoselective dihydroxylation
preferentially at the D8-double bond to give diol 42 togeth-
er with its 6,7-dihydroxy isomer in a ratio of 87:13; how-
ever, very high regioselectivity was not observed in this
case, unlike the dihydroxylation of 14 discussed above.
We first examined the key asymmetric pentenylation of
33 by following the procedures for asymmetric crotyla-
tion developed by Brown et al.30 (Table 3). When the re-
action was conducted by using a pentenylborane reagent
prepared from (2Z)-pent-2-en-1-ylmagnesium bromide
and
B-methoxydi(isopinocampheyl)borane
[(+)-
(Ipc)2BOMe], a 1:3 syn/anti mixture was unexpectedly
obtained, although the yield was almost quantitative (en-
try 1). This result suggests that a partial isomerization may
have taken place during the preparation of the Grignard
reagent from (2Z)-1-bromopent-2-ene. However, to our
delight, the use of the reagent prepared from pent-2-en-1-
ylpotassium and (+)-(Ipc)2BOMe allowed highly diaste-
reo- and enantioselective pentenylation to give the (S)-
syn-isomer 38 in 100% de and 93% ee in 81% yield (entry
2). In the reaction with a (2Z)-pent-2-en-1-ylboronate fol-
lowing Roush’s protocol,31 the enantioselectivity was un-
satisfactorily low, although the diastereoselectivity was
perfect (entry 3).
The diol 42 thus obtained was subjected to successive
acidic hydrolysis and allyloxycarbonylation in the same
flask to afford triol 43. After silylation of 43, exposure of
44 to Swern oxidation conditions36 allowed the direct pro-
duction of aldehyde 45 through selective cleavage of the
primary triethylsilyl ether group. Aldehyde 45 was then
converted into ynone 47 via 46 by ethynylation followed
by Dess–Martin oxidation.
The aminoethyl group was introduced at the C8 position
by means of the Suzuki–Miyaura coupling conditions de-
veloped by Overman et al.34 Thus, 38 was treated with 9-
{[N-(tert-butoxycarbonyl)amino]ethyl}-9-borabicyclonon-
ane, prepared in situ from tert-butyl vinylcarbamate in the
presence of [1,1¢-bis(diphenylphosphino)ferrocene](di-
chloro)palladium [PdCl2(dppf)] to give amino alcohol 39
stereoselectively. After acryloylation of 39, acrylate 40
was subjected to ring-closing metathesis using the sec-
ond-generation Grubbs catalyst in boiling dichloro-
By adopting the methodology employed for the synthesis
of fostriecin (1), we successfully converted ynone 47 into
the advanced intermediate 51 and three other isomers 52,
53, and 54 by Z- or E-selective addition of hydrogen io-
dide and 9-OH-directed anti- or syn-selective reduction,
as shown in Scheme 11.
Having secured reliable routes to 51 and all of its isomers
at the C11 stereocenter and the D12-double bond, we then
moved on to the final stage of the total synthesis of phos-
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2939
lactomycin B (2). In this particular case, Stille coupling of
51 with stannane 55 was low yielding under a variety of
conditions. However, we eventually found a reliable
method that gave 56 with good reproducibility (Table 4).
When 51 was treated with 55 in the presence of 0.3
equivalents of bis(acetonitrile)di(chloro)palladium
[Pd(MeCN)2Cl2] in acetonitrile–tetrahydrofuran (4:1) at
room temperature for 1 hour, 56 was obtained in 46%
yield, along with clean recovery of 51 (43%). After sepa-
ration, the recovered 51 was again subjected to these cou-
pling conditions to give 56 in >60% total yield. Similarly,
the other stereoisomers 57, 58, and 59 were also obtained
from 52, 53, and 54, respectively, in moderate yields (en-
tries 2–4).
B
NHBoc
COCl
PdCl2(dppf)
(5 mol%)
PMBO
PMBO
i-Pr2EtN
HO
HO
BocHN
3 M NaOH
1,4-dioxane
90%
CH2Cl2
0 °C
99%
I
39
38
Grubbs II
(10 mol%)
PMBO
OPMB
O
O
O
O
CH2Cl2, reflux
77%
BocHN
BocHN
41
40
OH OPMB
Super-AD-mix-
β
7
6,7-(OH)2-isomer
+
6
MeSO2NH2,
t-BuOH–H2O (1:1)
0 °C
O
O
OH
87:13
BocHN
42
Table 4 Stille Coupling of Diols 51–54 with Stannane 55
68% (73% brsm)
Super-AD-mix: K3Fe(CN)6, K2CO3,
(DHQD)2PHAL, K2OsO2(OH)4
(300:300:10:1)
SnBu3
OH OH
X
55
OH OH
*
*
Scheme 9 Preparation of diol 42
11
O
O
Y
Pd(MeCN)2Cl2
(30 mol%)
MeCN–THF (4:1)
1 h
Z
OTES
12
AllocHN
56: 11R,12Z
57: 11S,12Z
58: 11R,12E
59: 11S,12E
51: 11R, X = I, Y = H
52: 11S, X = I, Y = H
53: 11R, X = H, Y = I
54: 11S, X = H, Y = I
42: R1 = Boc, R2 = H
HCl, MeOH
then AllocCl
NaHCO3
R3 = PMB
98%
74%
OR2 OR3
43: R1 = Alloc, R2 = H
R3 = H
TESOTf
2,6-lutidine
CH2Cl2, –78 °C
O
O
Yield (%)b
Product
OR2
R1HN
44: R1 = Alloc
Entrya
Iodide
51
Recovered SMc
R2 = R3 = TES
46 (81d)
56
43
0
45: R = H, X = O
HC≡CMgBr
CeCl3, THF
–78 to –50 °C
1
2
3
4
56
57
58
59
Swern
oxidation
TESO
X
74%
52
46: R =
X = H(OH) (1:1)
H
O
O
R
DMP
CH2Cl2
OTES
84%
AllocHN
96%
NaHCO3
53
42 (57d)
52
26
0
47: R =
X = O
H
54
Scheme 10 Preparation of ynone 47
a All reactions were carried out at r.t. for 1 h.
b Isolated yield.
c Starting material.
d Based on recovered starting material.
method
A or B
TESO
O
TESO
O
X
O
O
O
O
AllocHN
Y
OTES
47
OTES
AllocHN
Finally, according to the procedure described in
Scheme 6, the total synthesis of (+)-phoslactomycin B (2)
was accomplished from 56 via 60, 61, and 62 by a four-
step sequence involving selective silylation of the C11 hy-
droxy group, phosphorylation of the C9 hydroxy group,
desilylation, and palladium-catalyzed deallylation.13a
Note that in the final deallylation, the reaction conditions
employed for the synthesis of fostriecin (1) were less ef-
fective, leading to a complex mixture. The spectral data
for the synthesized 2 showed good agreement with those
reported for the natural specimen.2c
method A: NaI (2 equiv), AcOH (1.1 equiv), acetone
48: X = I, Y = H, 98% (Z/E = 92:8)
method B: NaI (2 equiv), AcOH
49: X = I, Y = H, 79% (E exclusive)
Me4NBH(OAc)3
AcOH, MeCN
OR
O
I
OH OH
I
–30 °C
96%
O
O
O
O
OTES
OTES
AllocHN
AllocHN
51 (exclusive)
48: R = TES
50: X = H
AcOH
aq THF
89%
NaBH4, Et3B
THF–MeOH (6:1)
–78 °C
In conclusion, we have accomplished total syntheses of
(+)-fostriecin (1) and (+)-phoslactomycin B (2) in 4.5%
(21 steps) and 1.3% (26 steps) overall yields, respectively.
The synthetic method that we developed is flexible and of
potential value for the preparation of various analogues.
The synthesis of stereoisomers of 1 and 2 from 26, 27, 28,
57, 58, and 59 is currently under investigation.
OH OH
OTES
I
50
74%
O
O
AllocHN
52 (exclusive)
OH OH
*
53: 11R (80%, 2 steps)
54: 11S (60%, 2 steps)
11
49
O
O
I
OTES
AllocHN
Scheme 11 Preparation of advanced intermediate 51 and its isomers
Where appropriate, reactions were performed under an argon atmo-
sphere. All extracts were dried over MgSO4 and concentrated by ro-
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2940
S. Shibahara et al.
PAPER
FTIR (film): 1514, 1456, 1247, 1097, 1039 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.27 (d, J = 8.4 Hz, 2 H), 6.88 (d,
J = 8.4 Hz, 2 H), 5.53 (qt, J = 0.9, 6.6 Hz, J119Sn-H–J117Sn-
H = 69.6 Hz, 1 H), 4.46 (s, 2 H), 3.80 (s, 3 H), 3.47 (t, J = 6.6 Hz, 2
H), 2.45 (q, J = 6.6 Hz, 2 H), 1.84 (d, J = 0.9 Hz, J119Sn-H–J117Sn-
H = 49.2 Hz, 3 H), 1.48 (m, 6 H), 1.29 (m, 6 H), 0.89 (m, 15 H).
(H2C=CHCH2O)2P-N(i-Pr)2
tetrazole, CH2Cl2, 0 °C
TBSOTf
2,6-lutidine
OH OTBS
56
then 30% H2O2, 0 °C
94%
THF, –78 °C
95%
60
13C NMR (75 MHz, CDCl3): d = 159.2, 140.4, 136.4 (J119Sn-C–
O
PdCl2(PPh3)2
(5 mol%)
O
O
J
117Sn-C = 29.6 Hz), 129.3, 113.8, 29.2 (J119Sn-C–J117Sn-C = 19.3
P
O
OR2
(+)-PLM-B (2)
Bu3SnH
H2O/CH2Cl2
Hz), 28.9, 27.5 (J119Sn-C–J117Sn-C = 54.7 Hz), 19.3 (J119Sn-C–
J
117Sn-C = 42.8 Hz), 13.8, 9.16 (J119Sn-C = 342.8 Hz, J117Sn-
O
O
OR1
AllocHN
C = 311.9 Hz).
73%
MS (FAB, NBA): m/z = 439 [M – Bu+] for major 120Sn isotope.
61: R1 = TES, R2 = TBS
62: R1 = R2 = H
HF-pyridine,
H2O–MeCN
51%
(2E)-2-Iodo-5-[(4-methoxybenzyl)oxy]pent-2-ene (10)
I2 (9.52 g, 37.5 mmol) was added to an ice-cooled soln of stannane
9 (17.5 g, 35.6 mmol) in CH2Cl2 (170 mL), and the mixture was
stirred for 10 min at 0 °C. The reaction was quenched with sat. aq
NaHCO3 (50 mL) and 10% Na2S2O3 (50 mL). The mixture was ex-
tracted with Et2O, and the extracts were dried and concentrated. Pu-
rification of the residue by column chromatography [silica gel
pretreated with 8% Et3N–hexane (100 g), 4% Et3N–hexane] gave 10
as a pale yellow oil; yield: 11.82 g (quant).
Scheme 12 Completion of the total synthesis of phoslactomycin B
tary evaporation below 30 °C at 25 Torr, unless otherwise noted.
TLC was performed on glass-packed silica gel plates. Column chro-
matography was performed on silica gel. Optical rotations were re-
corded on a digital polarimeter at r.t. IR spectra were measured on
a Fourier-transform IR spectrometer. 1H NMR and 13C NMR spec-
tra were measured by using CDCl3, C6D6, or CD3OD as the solvent,
and chemical shifts are reported as d values in ppm based on internal
CHCl3 (7.26 ppm, 1H; 77.0 ppm, 13C), benzene (7.15 ppm, 1H; 128.0
ppm, 13C), H2O (4.65 ppm, 1H), or MeOH (49.9 ppm, 13C). HRMS
spectra were recorded in EI or FAB mode.
FTIR (film): 1610, 1510, 1450, 1360, 1242, 1085 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.7 Hz, 2 H), 6.87 (d,
J = 8.7 Hz, 2 H), 6.18 (tq, J = 7.4, 0.6 Hz, 1 H), 4.43 (s, 2 H), 3.80
(s, 3 H), 3.43 (t, J = 6.6 Hz, 2 H), 2.37 (d, J = 0.6 Hz, 3 H), 2.32 (dt,
J = 7.4, 6.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 159.3, 137.5, 130.4, 129.3, 113.9,
(3E)-4-(Tributylstannyl)pent-3-en-1-ol
95.4, 72.7, 68.4, 55.4, 34.3, 27.7.
A THF soln of (Bu3Sn)2CuCNLi2 was prepared as follows. A 1.56
M soln of BuLi in hexane (6.4 mL, 10 mmol) was slowly added to
a stirred soln of (Bu3Sn)2 (5.1 mL, 10 mmol) in THF (6 mL) at
–40 °C. After 15 min, the resulting soln was added to a suspension
of CuCN (447.6 mg, 5 mmol) in Et2O (10 mL) at –40 °C, and the
mixture was stirred at –25 °C for 1 h.
HRMS (EI): m/z calcd for C13H17IO2: 205.1224; found: 205.1242.
(2E,4E)-7-[(4-Methoxybenzyl)oxy]-4-methylhepta-2,4-dien-1-
al (11)
A soln of iodo derivative 10 (10.0 g, 30.1 mmol), acrolein (0.41 mL,
60.34 mmol), Bu4NCl (5.05 g, 18.20 mmol), K2CO3 (10.51 g, 76.14
mmol), and Pd(OAc)2 (119 mg, 0.593 mmol) in DMF (300 mL) was
stirred at r.t. for 4 h. The mixture was diluted with Et2O, washed
with H2O and brine, dried, and concentrated. Purification of the res-
idue by column chromatography [silica gel (300 g), hexane–
EtOAc, 5:1] gave 11 (5.71 g, 73%) as a colorless oil.
A THF soln of 2,3-dihydrofuran-2-yllithium was prepared as fol-
lows. A 1.47 M soln of t-BuLi in pentane (4.1 mL, 6 mmol) was
added to a stirred soln of 2,3-dihydrofuran (0.38 mL, 5 mmol) in
THF (5 mL) at –60 °C. After 10 min, the mixture was allowed to
warm to 0 °C and stirred for 50 min.
The THF soln of 2,3-dihydrofuran-2-yllithium was cooled to
–30 °C and added to the THF soln of (Bu3Sn)2CuCNLi2 at –30 °C.
The mixture was stirred at 0 °C for 1.5 h, allowed to warm to r.t.
over 1 h, and stirred at r.t. for 3 h. The reaction was quenched by the
addition of sat. aq NH4Cl (24 mL) and concd aq NH4OH (6 mL) at
0 °C. The mixture was stirred at 0 °C for 30 min then diluted with
Et2O. The extracts were washed with H2O and brine, dried, and con-
centrated. Purification of the residue by column chromatography
[silica gel pretreated with 8% Et3N in hexane (100 g), 1% Et3N–
hexane] gave (3E)-4-(tributylstannyl)pent-3-en-1-ol as a colorless
oil; yield: 1.55 g (63%). The spectral data (1H and 13C NMR) were
identical with those reported.18
FTIR (film): 1678, 1618, 1512, 1248, 1132, 1097 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.54 (d, J = 7.8 Hz, 1 H), 7.25 (d,
J = 8.7 Hz, 2 H), 7.10 (d, J = 15.6 Hz, 1 H), 6.87 (d, J = 8.7 Hz, 2
H), 6.09 (dd, J = 7.8, 15.6 Hz, 1 H), 6.05 (t, J = 6.6 Hz, 1 H), 4.45
(s, 2 H), 3.77 (s, 3 H), 3.54 (t, J = 6.6 Hz, 2 H), 2.53 (q, J = 6.6 Hz,
2 H), 1.80 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 193.9, 159.0, 157.3, 140.5, 134.6,
130.1, 129.1, 126.8, 113.6, 72.5, 68.3, 55.0, 29.6, 12.2.
HRMS (EI): m/z calcd for C16H20O3: 260.1412; found: 260.1424.
(4R,5E,7E)-10-[(4-Methoxybenzyl)oxy]-7-methyldeca-1,5,7-
trien-4-ol (12)
(2E)-2-(Tributylstannanyl)-5-[(4-methoxybenzyl)oxy]pent-2-
ene (9)
A 1.0 M soln of allylmagnesium bromide in Et2O (22 mL, 22 mmol)
was added to a stirred soln of (+)-B-methoxy(diisopinocam-
pheyl)borane (6.80 g, 21.6 mmol) in Et2O (25 mL) at –78 °C. After
15 min, the mixture was allowed to warm to r.t. and stirred for 11 h.
The resulting soln was added through a cannula to a mixture of al-
dehyde 11 (3.47 g, 13.7 mmol) and 4-Å molecular sieves (2.00 g) in
toluene (40 mL) at –78 °C, and the mixture was stirred for 6 h at
–78 °C. 3 M aq NaOH (40 mL) and THF (40 mL) were then added,
and the mixture was allowed to warm to 0 °C and treated with 30%
H2O2 (20 mL). After being stirred at r.t. overnight, the mixture was
diluted with 3 M NaOH (100 mL) and extracted with Et2O. The ex-
NaH (60% in oil; 1.75 g, 43.8 mmol) was added to a soln of (3E)-4-
(tributylstannyl)pent-3-en-1-ol (10.9 g, 29.1 mmol) in DMSO (100
mL) at 0 °C, and the mixture was stirred at r.t. for 1.5 h. Bu4NI
(328.7 mg, 0.890 mmol) and PMBCl (5.5 mL, 40.6 mmol) were
added, and the mixture was stirred overnight. The mixture was then
diluted with ice-water (200 mL) and extracted with Et2O. The ex-
tracts were washed with brine, dried, and concentrated. Purification
of the residue by column chromatography [silica gel pretreated with
8% Et3N–hexane (100 g), 4% Et3N–hexane] gave 9 as a pale yellow
oil; yield: 13.0 g (90%).
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2941
tracts were washed with H2O and brine, dried, and concentrated. Pu-
rification of the residue by column chromatography [silica gel (200
g), hexane–EtOAc, 8:1 to 4:1] gave 12 as a pale yellow oil; yield:
3.26 g (81%); [a]D23 +5.3 (c 1.05, CHCl3).
(6R)-6-[(1E,3R,4R)-3,4-Dihydroxy-6-[(4-methoxybenzyl)oxy]-
3-methyl-hex-1-en-1-yl]-5,6-dihydro-2H-pyran-2-one (16)
AD-mix-b (6.68 g) was added to an ice-cooled soln of 14 (1.09 g,
3.34 mmol) and MeSO2NH2 (321 mg, 3.37 mmol) in 1:1 t-BuOH–
H2O (40 mL), and the mixture was stirred at 0 °C for 6 h. The mix-
ture was then diluted with sat. aq Na2S2O3 (15 mL) and extracted
with EtOAc. The extracts were washed with brine (10 mL), dried,
and concentrated. The residue was purified by column chromatog-
raphy [silica gel (50 g), Et2O] gave 16 as a pale yellow oil; yield:
FTIR (film): 3404, 1612, 1512, 1244, 1088, 1033 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.26 (d, J = 8.4 Hz, 2 H), 6.88 (d,
J = 8.4 Hz, 2 H), 6.25 (d, J = 15.9 Hz, 1 H), 5.82 (m, 1 H), 5.60 (dd,
J = 6.6, 15.6 Hz, 1 H), 5.50 (t, J = 7.2 Hz, 1 H), 5.16 (br d, J = 7.5
Hz, 1 H), 5.12 (s, 1 H), 4.45 (s, 2 H), 4.22 (q, J = 6.6 Hz, 1 H), 3.80
(s, 3 H), 3.47 (t, J = 6.9 Hz, 2 H), 2.45 (q, J = 6.9 Hz, 2 H), 2.33 (m,
2 H), 1.75 (s, 3 H).
20
965 mg (80%); [a]D +34.7 (c 0.99, CHCl3). This compound was
shown to be enantiomerically pure by 1H NMR (500 MHz) analysis
of the corresponding (R)- and (S)-MTPA esters.
13C NMR (75 MHz, CDCl3): d = 159.2, 135.5, 134.6, 134.4, 130.6,
129.3, 129.1, 128.9, 118.2, 113.8, 72.7, 72.0, 69.3, 55.3, 42.2, 29.1,
12.6.
FTIR (film): 3496, 1707, 1248 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.23 (d, J = 8.7 Hz, 2 H), 6.87 (d,
J = 8.7 Hz, 2 H), 6.86 (m, 1 H), 6.02 (dt, J = 9.9, 1.2 Hz, 1 H), 5.95
(d, J = 15.6 Hz, 1 H), 5.87 (dd, J = 5.1, 15.6 Hz, 1 H), 4.93 (dt,
J = 9.9, 5.1 Hz, 1 H), 4.44 (s, 2 H), 3.79 (s, 3 H), 3.67 (m, 3 H), 3.48
(br s, 1 H), 2.78 (br s, 1 H), 2.43 (m, 2 H), 1.75 (m, 2 H), 1.23 (s, 3
H).
HRMS (EI): m/z calcd for C19H26O3: 302.1882; found: 302.1873.
(4R,5E,7E)-10-[(4-Methoxybenzyl)oxy]-7-methyldeca-1,5,7-
trien-4-yl Acrylate (13)
Acryloyl chloride (0.69 mL, 8.67 mmol) was added to an ice-cooled
soln of trienol 12 (2.28 g, 7.54 mmol) and Et3N (1.27 mL, 9.05
mmol) in CH2Cl2 (22 mL), and the mixture was stirred for 40 min
at 0 °C. The mixture was then poured into sat. aq NaHCO3 (350 mL)
and extracted with CH2Cl2. The extracts were dried, and concentrat-
ed, and the residue was purified by column chromatography [silica
gel (60 g) hexane–EtOAc, 3:1] to give 13 as a colorless oil; yield:
2.14 g (80%); [a]D21 +2.9 (c 1.03, CHCl3).
13C NMR (75 MHz, CDCl3): d = 164.1, 159.4, 144.9, 138.5, 129.7,
129.5, 126.1, 121.5, 113.9, 76.9, 74.3, 73.1, 69.0, 55.3, 29.9, 28.7,
26.9, 22.8.
MS (FAB, NBA): m/z = 363 [M + H+].
(6R)-6-[(1E,3R,4R)-6-[(4-Methoxybenzyl)oxy]-3-methyl-3,4-
bis[(triethylsilyl)oxy]hex-1-en-1-yl]-5,6-dihydro-2H-pyran-2-
one (17)
FTIR (film): 1722, 1512, 1250, 1190, 1095, 1037, 966, 815 cm–1.
TESOTf (1.3 mL, 5.75 mmol) was added to a soln of 16 (851 mg,
2.35 mmol) and 2,6-lutidine (0.82 mL, 7.04 mmol) in CH2Cl2 (17
mL) at –78 °C, and the mixture was stirred at –78 °C for 30 min.
The reaction was then quenched with sat. aq NaHCO3 (100 mL),
and the mixture was extracted with CH2Cl2. The extracts were dried
and concentrated to give a residue that was purified by column chro-
matography [silica gel (30 g), hexane–EtOAc, 5:1] to give 17 as a
colorless oil; yield: 1.26 g (91%); [a]D18 +36.5 (c 1.04, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.26 (d, J = 8.4 Hz, 2 H), 6.88 (d,
J = 8.4 Hz, 2 H), 6.40 (dd, J = 1.5, 17.4 Hz, 1 H), 6.30 (d, J = 15.6
Hz, 1 H), 6.11 (dd, J = 10.5, 17.4 Hz, 1 H), 5.81 (dd, J = 1.5, 10.5
Hz, 1 H), 5.74 (m, 1 H), 5.53 (dd, J = 6.9, 15.6 Hz, 1 H), 5.53 (t,
J = 6.9 Hz, 1 H), 5.43 (q, J = 6.9 Hz, 1 H), 5.10 (br d, J = 15.9 Hz,
1 H), 5.07 (br d, J = 9.6 Hz, 1 H), 4.44 (s, 2 H), 3.80 (s, 3 H), 3.46
(t, J = 6.9 Hz, 2 H), 2.44 (q, J = 6.9 Hz, 4 H), 1.73 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 165.5, 159.2, 137.7, 134.4, 133.4,
130.7, 130.5, 130.2, 129.4, 128.9, 124.2, 118.0, 113.8, 74.3, 72.7,
69.3, 55.3, 39.3, 29.1, 12.5.
FTIR (film): 1730, 1514, 1246, 1105, 1007 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.4 Hz, 2 H), 6.87 (d,
J = 8.4 Hz, 2 H), 6.86 (m, 1 H), 6.04 (dt, J = 9.6, 1.7 Hz, 1 H), 5.92
(d, J = 15.9 Hz, 1 H), 5.76 (dd, J = 6.6, 15.9 Hz, 1 H), 4.92 (q,
J = 7.2 Hz, 1 H), 4.40 (s, 2 H), 3.80 (s, 3 H), 3.58 (dd, J = 3.6, 7.8
Hz, 1 H), 3.45 (dd, J = 6.3, 7.8 Hz, 2 H), 2.40 (m, 2 H), 1.94 (ddt,
J = 3.6, 14.1, 7.8 Hz, 1 H), 1.41 (ddt, J = 7.8, 14.1 Hz, 1 H), 6.3,
1.33 (s, 3 H), 0.942 (t, J = 7.8 Hz, 9 H), 0.937 (t, J = 7.8 Hz, 9 H),
0.59 (q, J = 7.8 Hz, 6 H), 0.58 (q, J = 7.8 Hz, 6 H).
MS (FAB, NBA): m/z = 379 [M + Na+].
(6R)-6-{(1E,3E)-6-[(4-Methoxybenzyloxy)]-3-methylhexa-1,3-
dien-1-yl}-5,6-dihydro-2H-pyran-2-one (14)
[(Cy3P)2Cl2Ru=CHPh] (103 mg, 0.125 mmol) was added to a de-
gassed soln of acrylate 13 (444 mg, 1.25 mmol) in CH2Cl2 (125
mL), and the mixture was refluxed for 20 h. The mixture was then
concentrated and subjected to chromatography [silica gel (25 g),
hexane–EtOAc, 3:1] to give dienone 14 as a pale yellow oil [yield:
306 mg (75%)], together with dimer 15 (34 mg, 4%). The optical
purity of 14 was determined to be 77% ee by HPLC (Chiralcel OD,
Daicel, i-PrOH–hexane, 1:4); [a]D22 +22.8 (c 1.09, CHCl3).
13C NMR (75 MHz, CDCl3): d = 164.3, 159.1, 144.8, 138.3, 129.3,
125.6, 121.7, 113.7, 78.1, 77.8, 76.9, 72.5, 67.5, 55.3, 33.4, 29.9,
25.6, 7.2, 7.1, 6.9, 5.4.
MS (FAB, NBA): m/z = 363 [M + H+].
(6R)-6-[(1E,3R,4R)-6-Hydroxy-3-methyl-3,4-bis[(triethyl-
silyl)oxy]hex-1-en-1-yl]-5,6-dihydro-2H-pyran-2-one (18)
DDQ (344 mg, 0.731 mmol) was added to an ice-cooled soln of 17
(356 mg, 0.603 mmol) in 20:1 CH2Cl2/H2O (27 mL), and the mix-
ture was stirred for 1 h, The mixture was then diluted with sat. aq
NaHCO3 (50 mL) and extracted with CH2Cl2. The extracts were
washed with H2O and brine, dried, and concentrated. Purification of
the residue by column chromatography [silica gel (10 g), hexane–
EtOAc, 4:1 to 3:1] gave 18 as a colorless oil; yield: 282 mg (99%);
[a]D23 +42.8 (c 1.01, CHCl3).
FTIR (film): 1714, 1512, 1381, 1240 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.4 Hz, 2 H), 6.89 (m,
1 H), 6.87 (d, J = 8.4 Hz, 2 H), 6.34 (d, J = 15.9 Hz, 1 H), 6.04 (dt,
J = 1.8, 9.6 Hz, 1 H), 5.64 (dd, J = 6.9, 15.9 Hz, 1 H), 5.57 (t, J = 7.5
Hz, 1 H), 4.96 (q, J = 6.9 Hz, 1 H), 4.44 (s, 2 H), 3.79 (s, 3 H), 3.47
(t, J = 6.9 Hz, 2 H), 2.44 (m, 4 H), 1.74 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.1, 159.2, 144.8, 138.2, 134.1,
131.2, 130.5, 129.3, 123.0, 121.7, 113.8, 78.5, 72.7, 69.2, 55.3,
30.0, 29.1, 12.5.
FTIR (film): 3448, 1724, 1459, 1381, 1244, 1105, 1012 cm–1.
MS (FAB, NBA): m/z = 351 [M + Na+].
1H NMR (300 MHz, CDCl3): d = 6.88 (dt, J = 3.9, 9.6 Hz, 1 H), 6.05
(dt, J = 1.5, 9.9 Hz, 1 H), 5.93 (dd, J = 0.9, 15.9 Hz, 1 H), 5.77 (dd,
J = 6.3, 15.9 Hz, 1 H), 4.96 (q, J = 6.3 Hz, 1 H), 3.671 (br quint,
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2942
S. Shibahara et al.
PAPER
J = 5.1 Hz, 2 H), 2.45 (m, 2 H), 1.95 (br t, J = 5.1 Hz, 1 H), 1.86 (m,
1 H), 1.58 (d, J = 2.4 Hz, 3 H), 1.53 (m, 1 H), 0.97 (t, J = 8.1 Hz, 9
H), 0.96 (t, J = 8.1 Hz, 9 H), 0.63 (q, J = 8.1 Hz, 6 H), 0.62 (q,
J = 8.1 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 164.1, 144.7, 138.0, 125.8, 121.59,
78.0, 77.9, 77.7, 60.2, 36.4, 29.8, 25.4, 7.1, 7.0, 6.8, 5.2.
FTIR (film): 3429, 3309, 1724, 1382, 1242, 1105 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.88 (dt, J = 3.6, 9.9 Hz, 1 H), 6.05
(dt, J = 9.9, 1.5 Hz, 1 H), 5.94 (dd, J = 0.6, 15.9 Hz, 1 H), 5.77 (dd,
J = 6.3, 15.9 Hz, 1 H), 4.96 (ddt, J = 0.6, 7.8, 6.3 Hz, 1 H), 4.45 (br
q, J = 4.2 Hz, 1 H), 3.79 (dd, J = 5.1, 6.3 Hz, 1 H), 2.46 (m, 3 H),
2.02 (ddd, J = 5.1, 6.9, 14.1 Hz, 1 H), 1.70 (dt, J = 14.1, 6.3 Hz, 1
H), 1.40 (s, 3 H), 1.25 (s, 1 H), 0.97 (t, J = 8.1 Hz, 18 H), 0.65 (q,
J = 8.1 Hz, 12 H).
MS (FAB, NBA): m/z = 493 [M + Na+].
(3R,4R,5E)-4-Methyl-6-[(2R)-6-oxo-3,6-dihydro-2H-pyran-2-
yl]-3,4-bis[(triethylsilyl)oxy]hex-5-enal (19)
13C NMR (75 MHz, CDCl3): d = 164.1, 144.7, 137.6, 126.3, 121.7,
84.9, 78.1, 77.8, 76.8, 73.5, 60.3, 41.6, 30.0, 25.5, 7.2, 7.1, 6.9, 5.4.
Dess–Martin periodinane (2.70 g, 6.38 mmol) was added to an ice-
cooled soln of 18 (997 mg, 2.12 mmol) in CH2Cl2 (20 mL) was add-
ed, and the mixture was stirred at 0 °C for 1 h. The reaction was then
quenched with sat. aq NaHCO3 (50 mL) and 10% aq Na2S2O3 (50
mL), and the mixture was extracted with EtOAc. The extracts were
washed with sat. aq NaHCO3 and brine then dried and concentrated.
Purification of the residue by column chromatography [silica gel
(10 g), hexane–EtOAc, 3:1] gave 19 as a colorless oil: yield: 996 mg
(quant); [a]D24 +42.5 (c 1.00, CHCl3).
MS (FAB, NBA): m/z = 517 [M + Na+].
(6R)-6-{(1E,3R)-3-Methyl-6-oxo-3,4-bis[(triethylsilyl)oxy]oct-
1-en-7-yn-1-yl}-5,6-dihydro-2H-pyran-2-one (21)
Dess–Martin periodinane (3.78 g, 8.90 mmol) was added to an ice-
cooled soln of alkynol 20 (887 mg, 1.80 mmol) in CH2Cl2 (40 mL),
and the mixture was stirred at 0 °C for 4 h. The reaction was
quenched with sat. aq NaHCO3 (120 mL) and 10% Na2S2O3 (60
mL), and then the mixture was extracted with EtOAc. The extracts
were washed with sat. aq NaHCO3 and brine, then dried and con-
centrated. Purification of the residue by column chromatography
[silica gel (20 g), 20% EtOAc–hexane] gave 21 as a colorless oil;
yield: 841 mg (95%); [a]D24 +56.2 (c 1.05, CHCl3).
FTIR (film): 1728, 1240, 1107, 1011 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.70 (t, J = 2.1 Hz, 1 H), 6.89
(ddd, J = 4.5, 5.1, 9.6 Hz, 1 H), 6.05 (dt, J = 2.1, 9.9 Hz, 1 H), 5.93
(d, J = 15.6 Hz, 1 H), 5.78 (dd, J = 6.3, 15.6 Hz, 1 H), 4.97 (dt,
J = 6.3, 8.7 Hz, 1 H), 4.03 (dd, J = 5.1, 6.0 Hz, 1 H), 2.62 (ddd,
J = 2.1, 6.0, 16.5 Hz, 1 H), 2.45 (m, 2 H), 2.36 (ddd, J = 2.1, 5.1,
16.5 Hz, 1 H), 1.40 (s, 3 H), 0.95 (t, J = 7.8 Hz, 9 H), 0.94 (t, J = 7.8
Hz, 9 H), 0.62 (q, J = 7.8 Hz, 6 H), 0.59 (q, J = 7.8 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 200.5, 164.1, 144.7, 137.0, 128.3,
126.8, 121.1, 77.6, 75.2, 47.9, 29.8, 25.6, 6.9, 4.99.
MS (FAB, NBA): m/z = 491 [M + Na+].
IR (film): 1730, 1682, 1460, 1383, 1244, 1111, 1007 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.88 (ddd, J = 3.6, 4.8, 9.6 Hz, 1
H), 6.03 (ddd, J = 1.5, 2.1, 9.6 Hz, 1 H), 5.88 (d, J = 15.6 Hz, 1 H),
5.78 (dd, J = 5.7, 15.6 Hz, 1 H), 4.96 (dt, J = 5.7, 9.3 Hz, 1 H), 4.17
(dd, J = 4.8, 6.6 Hz, 1 H), 3.22 (s, 1 H), 2.89 (dd, J = 4.8, 16.5 Hz,
1 H), 2.45 (m, 2 H), 2.40 (dd, J = 6.6, 16.5 Hz, 1 H), 1.38 (s, 3 H),
0.92 (t, J = 8.1 Hz, 9 H), 0.93 (t, J = 8.1 Hz, 9 H), 0.59 (q, J = 8.1
Hz, 12 H).
3-{(1E,3R,4S,6R)- and 3-{(1E,3R,4S,6S)-6-Hydroxy-3-methyl-
3,4-bis[(triethylsilyl)oxy]oct-1-en-7-yn-1-yl]-5,6-dihydro-2H-
pyran-2-one (20)
13C NMR (75 MHz, CDCl3): d = 185.3, 164.2, 144.7, 136.9, 126.6,
121.7, 81.9, 78.6, 77.6, 77.3, 75.2, 50.0, 29.9, 25.6, 7.2, 7.0, 6.8, 5.1.
HRMS (EI): m/z calcd for C26H44O5Si2: 492.2727; found: 492.2776.
Commercial anhyd CeCl3 (609 mg, 2.47 mmol) was heated under
vacuum at 140 °C for 2 h. THF (6 mL) was added, and the resulting
suspension was stirred at r.t. for 18 h. A 0.5 M soln of ethynylmag-
nesium bromide in THF (4.9 mL, 2.45 mmol) was added to the sus-
pension over 5 min at –78 °C, and the mixture was stirred at –78 °C
for 1 h. A soln of enal 19 (366 mg, 0.781 mmol) in THF (5 mL) was
added over 7 min at –78 °C. After 10 min, the mixture was allowed
to warm to –50 °C then stirred for 50 min. The reaction was
quenched with H2O (15 mL) and the mixture was filtered through
Celite. The filtrate was extracted with Et2O, and the extracts were
washed with H2O, dried, and concentrated. Purification of the resi-
due by column chromatography [silica gel (15 g), hexane–
EtOAc, 4:1 to 3:1] gave 20 as a colorless oil; yield: 379 mg (98%;
epimeric mixture 6R/6S = 1:1.8). The following data were collected
after separation of the epimers by flash column chromatography.
(6R)-6-{(1E,3R,4R,7Z)-8-Iodo-3-methyl-6-oxo-3,4-bis[(triethyl-
silyl)oxy]octa-1,7-dien-1-yl]-5,6-dihydro-2H-pyran-2-one (22)
NaI (115 mg, 0.770 mmol) was added to a soln of ynone 21 (190
mg, 0.385 mmol) and AcOH (23 ml, 0.400 mmol) in acetone (0.4
mL) at r.t., and the mixture was stirred for 3 days. The mixture was
basified with sat. aq NaHCO3 (10 mL) and extracted with EtOAc.
The extracts were dried and concentrated to give a residue that was
purified flash column chromatography [silica gel (20 g), benzene]
to give (Z)-isomer 22 [yield: 150 mg (63%)] and (E)-isomer 23
[yield: 15 mg (6%)], each as a yellow oil.
(7Z)-Isomer 22: [a]D23 +54.6 (c 0.97, CHCl3).
FTIR (film): 1726, 1240, 1091, 1008 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.7 Hz, 1 H), 7.17 (d,
J = 8.7 Hz, 1 H), 6.89 (ddd, J = 3.6, 5.1, 9.6 Hz, 1 H), 6.05 (dt,
J = 9.6, 1.8 Hz, 1 H), 5.93 (dd, J = 0.6, 15.9 Hz, 1 H), 5.79 (dd,
J = 5.7, 15.9 Hz, 1 H), 4.97 (dt, J = 5.7, 8.7 Hz, 1 H), 4.18 (dd,
J = 3.6, 6.9 Hz, 1 H), 2.86 (dd, J = 3.6, 17.4 Hz, 1 H), 2.46 (m, 2 H),
2.38 (dd, J = 6.9, 17.4 Hz, 1 H), 1.38 (s, 3 H), 0.91 (t, J = 7.8 Hz, 18
H), 0.59 (q, J = 7.8 Hz, 6 H), 0.57 (q, J = 7.8 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 197.1, 164.2, 144.7, 137.4, 126.0,
121.7, 90.5, 77.6, 77.3, 75.0, 48.5, 29.8, 25.6, 7.2, 7.1, 6.8, 5.1.
MS (FAB, NBA): m/z = 643 [M + Na+].
(R)-Isomer: [a]D24 +46.0 (c 1.03, CHCl3).
FTIR (film): 3440, 3309, 1722, 1382, 1242, 1103, 1009 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.89 (ddd, J = 4.2, 5.1, 9.9 Hz, 1
H), 6.05 (dt, J = 9.9, 1.5 Hz, 1 H), 5.93 (dd, J = 0.6, 15.6 Hz, 1 H),
5.78 (dd, J = 6.3, 15.6 Hz, 1 H), 4.97 (ddt, J = 0.6, 6.0, 8.1 Hz, 1 H),
4.48 (br d, J = 9.6 Hz, 1 H), 3.75 (dd, J = 4.8, 6.9 Hz, 1 H), 2.46 (m,
2 H), 2.40 (br s, 1 H), 2.02 (ddd, J = 4.8, 9.6, 14.1 Hz, 1 H), 1.62
(ddd, J = 3.6, 6.9, 14.1 Hz, 1 H), 1.38 (s, 3 H), 1.25 (s, 1 H), 0.97 (t,
J = 8.1 Hz, 9 H), 0.96 (t, J = 8.1 Hz, 9 H), 0.65 (q, J = 8.1 Hz, 6 H),
0.63 (q, J = 8.1 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 164.2, 144.7, 137.7, 126.3, 121.8,
85.4, 77.9, 72.6, 59.6, 41.7, 29.9, 25.5, 7.2, 7.1, 6.9, 5.4.
MS (FAB, NBA): m/z = 517 [M + Na+].
(S)-Isomer: [a]D17 +25.8 (c 1.00, CHCl3).
(6R)-6-[(1E,3R,4R,7E)-8-Iodo-3-methyl-6-oxo-3,4-bis[(triethyl-
silyl)oxy]octa-1,7-dienyl]-5,6-dihydro-2H-pyran-2-one (23)
NaI (196 mg, 1.31 mmol) was added to a soln of ynone 21 (158 mg,
0.321 mmol) in AcOH (0.4 mL) at r.t. The mixture was stirred for 3
h then poured into a mixture of sat. aq NaHCO3 (50 mL) and 10%
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2943
aq Na2S2O3 (20 mL) at 0 °C. The mixture was extracted with
EtOAc, and the extracts were washed with sat. aq NaHCO3 and
brine, dried, and concentrated. Purification of the residue by column
chromatography [silica gel (6 g), hexane–EtOAc (5:1) containing
1% Et3N to hexane–EtOAc (4:1) containing 1% Et3N] gave 23 as a
yellow oil; yield: 162 mg (81%); [a]D23 +53.1 (c 1.01, CHCl3).
Hz, 1 H), 1.33 (s, 3 H), 0.94 (t, J = 7.8 Hz, 9 H), 0.59 (q, J = 7.8 Hz,
6 H).
13C NMR (75 MHz, CDCl3): d = 163.8, 144.5, 143.5, 137.8, 127.6,
121.8, 81.4, 77.4, 77.3, 75.2, 72.7, 35.4, 29.6, 20.8, 7.1, 6.7.
MS (FAB, NBA): m/z 531 [M + Na+].
FTIR (film): 1728, 1690, 1567, 1379, 1242, 1097, 1010 cm–1.
(6R)-6-[(1E,3R,4R,6S,7Z)-4,6-Dihydroxy-8-iodo-3-methyl-3-
[(triethylsilyl)oxy]octa-1,7-dien-1-yl}-5,6-dihydro-2H-pyran-2-
one (26)
1H NMR (300 MHz, CDCl3): d = 7.73 (d, J = 15.0 Hz, 1 H), 7.08 (d,
J = 15.0 Hz, 1 H), 6.87 (ddd, J = 3.3, 5.1, 9.6 Hz, 1 H), 6.02 (dt,
J = 9.6, 1.2 Hz, 1 H), 5.90 (d, J = 16.5 Hz, 1 H), 5.76 (dd, J = 5.7,
16.5 Hz, 1 H), 4.95 (dt, J = 5.7, 9.3 Hz, 1 H), 4.09 (dd, J = 3.6, 6.9
Hz, 1 H), 2.78 (dd, J = 3.6, 16.5 Hz, 1 H), 2.45 (m, 2 H), 2.31 (dd,
J = 6.9, 16.5 Hz, 1 H), 1.34 (s, 3 H), 0.89 (t, J = 7.5 Hz, 18 H), 0.54
(q, J = 7.5 Hz, 12 H).
13C NMR (75 MHz, CDCl3): d = 195.7, 164.1, 145.3, 144.6, 137.2,
126.1, 121.6, 98.8, 77.4, 77.3, 75.2, 44.4, 29.8, 25.6, 7.1, 6.9, 6.7,
5.0.
A 0.11 M soln of Et3B in 4:1 MeOH–THF (0.7 mL, 0.077 mmol)
and NaBH4 (3.0 mg, 0.079 mmol) were added to a soln of enone 24
(32 mg, 0.063 mmol) in THF (0.25 mL) at –78 °C, and the mixture
was stirred at –78 °C for 14 h. 30% H2O2 (0.32 mL) was added, fol-
lowed by MeOH (1 mL), EtOAc (1 mL), and sat. aq NaHCO3 (1
mL) at r.t. The mixture was stirred for 10 min then extracted with
EtOAc. The extracts were dried and concentrated to give a residue
that was purified by preparative TLC (hexane–EtOAc, 1:1) to give
27
26 as a colorless oil; yield: 29 mg (90%); [a]D –88.0 (c 0.30,
MS (FAB, NBA): m/z = 643 [M + Na+].
CHCl3).
FTIR (film): 3435, 1712, 1382, 1247, 1084 cm–1.
(6R)-6-{(1E,3R,4S,7E)-4-Hydroxy-8-iodo-3-methyl-6-oxo-3-
[(triethylsilyl)oxy]octa-1,7-dien-1-yl}-5,6-dihydro-2H-pyran-2-
one (24)
1H NMR (300 MHz, CDCl3): d = 6.89 (ddd, J = 3.6, 5.1, 9.9 Hz, 1
H), 6.30 (m, 2 H), 6.07 (td, J = 2.0, 10.0 Hz, 1 H), 5.90 (d, J = 16.8
Hz, 1 H), 5.81 (dd, J = 5.4, 16.8 Hz, 1 H), 4.97 (td, J = 5.4, 9.9 Hz,
1 H), 4.56 (br d, J = 9.3 Hz, 1 H), 3.69 (td, J = 2.1, 10.8 Hz, 1 H),
3.53 (d, J = 1.2 Hz, 1 H), 3.03 (br dd, J = 1.2, 2.4 Hz, 1 H), 2.46 (m,
2 H), 1.68 (br d, J = 14.1 Hz, 1 H), 1.40–1.55 (m, 1 H), 1.33 (s, 3
H), 0.95 (t, J = 8.1 Hz, 9 H), 0.61 (q, J = 8.1 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 163.8, 144.4, 143.4, 137.4, 127.9,
81.7, 77.4, 76.9, 75.5, 35.8, 29.7, 20.8, 7.2, 6.7.
MS (FAB, NBA): m/z = 531 [M + Na+].
A soln of (Z)-isomer 22 (221 mg, 0.356 mmol) in 47% HF–pyri-
dine–H2O–MeCN (1:4:2:20; 77 mL) was stirred with cooling in an
ice bath for 8 h. The mixture was then basified with sat. aq NaHCO3
(50 mL) and extracted with EtOAc. The extracts were dried and
concentrated to give a residue that was purified by column chroma-
tography [silica gel (5 g), hexane–EtOAc, 2:1 containing 1% Et3N]
to give 24 as a yellow oil; yield: 146 mg (81%); [a]D24 +39.4 (c 1.00,
CHCl3).
FTIR (film): 3471, 1718, 1697, 1568, 1458, 1381, 1244, 1076 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35 (d, J = 8.7 Hz, 1 H), 7.26 (d,
J = 8.7 Hz, 1 H), 6.89 (ddd, J = 3.6, 4.8, 9.9 Hz, 1 H), 6.05 (dt,
J = 1.5, 9.9 Hz, 1 H), 5.91 (d, J = 15.9 Hz, 1 H), 5.82 (dd, J = 5.0,
15.9 Hz, 1 H), 4.96 (dt, J = 5.4, 9.3 Hz, 1 H), 3.96 (ddd, J = 2.1, 3.1,
9.6 Hz, 1 H), 2.92 (d, J = 3.6 Hz, 1 H), 2.79 (dd, J = 2.1, 17.4 Hz, 1
H), 2.51 (dd, J = 9.6, 17.4 Hz, 1 H), 2.43–2.48 (m, 2 H), 1.39 (s, 3
H), 0.94 (t, J = 8.1 Hz, 9 H), 0.59 (q, J = 8.1 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 199.0, 164.0, 144.6, 137.1, 135.4,
127.3, 121.7, 91.8, 77.4, 76.7, 74.6, 45.7, 29.5, 23.1, 7.2, 6.7.
MS (FAB, NBA): m/z = 529 [M + Na+].
(6R)-6-{(1E,3R,4R,6R,7E)-4,6-Dihydroxy-8-iodo-3-methyl-3-
[(triethylsilyl)oxy]octa-1,7-dien-1-yl}-5,6-dihydro-2H-pyran-2-
one (27)
Compound 23 was desilylated in the same manner as described for
the preparation of 24 from 22 to give the corresponding hydroxy ke-
tone in 80% yield: [a]D19 +49.8 (c 1.00, CHCl3).
IR (film): 3446, 1718, 1568, 1381, 1244, 1078 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.88 (d, J = 15.0 Hz, 1 H), 7.18
(d, J = 15.0 Hz, 1 H), 6.90 (ddd, J = 3.9, 5.1, 9.6 Hz, 1 H), 6.06 (dt,
J = 1.5, 9.6 Hz, 1 H), 5.91 (d, J = 15.9 Hz, 1 H), 5.82 (dd, J = 5.4,
15.9 Hz, 1 H), 4.96 (dt, J = 5.4, 9.3 Hz, 1 H), 3.90 (dq, J = 2.1, 9.6
Hz, 1 H), 2.86 (d, J = 3.3 Hz, 1 H), 2.72 (dd, J = 2.1, 16.5 Hz, 1 H),
2.48 (dd, J = 9.6, 17.4 Hz, 1 H), 2.43–2.47 (m, 2 H), 1.39 (s, 3 H),
0.94 (t, J = 8.1 Hz, 9 H), 0.59 (q, J = 8.1 Hz, 6 H).
(6R)-6-{(1E,3R,4R,6R,7Z)-4,6-Dihydroxy-8-iodo-3-methyl-3-
[(triethylsilyl)oxy]octa-1,7-dien-1-yl}-5,6-dihydro-2H-pyran-2-
one (25)
A soln of Me4NBH(OAc)3 (180 mg, 0.685 mmol) and AcOH (0.14
mL) in MeCN (0.1 mL) was stirred for 30 min. To the mixture was
added a soln of enone 24 (43 mg, 0.084 mmol) in MeCN (1.1 mL)
at –40 °C, and the resulting mixture was allowed to warm to –30 °C
and stirred at –30 °C for 1 week. 20% aq Rochelle’s salt (5 mL) and
sat. aq NaHCO3 (5 mL) were added and the mixture was stirred at
r.t. for 30 min. The mixture was then extracted with EtOAc, and the
extracts were dried, and concentrated to give a residue that was pu-
rified by preparative TLC (hexane–EtOAc, 1:1) to give 25 as a col-
orless oil; yield: 43 mg (99%; epimeric mixture 11R/11S = 92:8);
[a]D25 +58.8 (c 1.05, CHCl3).
13C NMR (75 MHz, CDCl3): d = 197.3, 163.9, 144.8, 144.6, 137.1,
127.4, 121.8, 100.3, 77.4, 76.8, 74.6, 41.9, 29.6, 23.1, 7.2, 6.7.
MS (FAB, NBA): m/z = 529 [M + Na+].
Reduction of the hydroxy ketone with Me4NBH(OAc)3 in the same
manner as described for the preparation of 25 from 24 gave com-
27
pound 27 as a colorless oil; yield: 98%; [a]D +28.8 (c 0.68,
CHCl3).
IR (film): 3423, 1712, 1245 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.90 (ddd, J = 3.5, 5.1, 9.6 Hz, 1
H), 6.57 (dd, J = 3.6, 5.1, 9.6 Hz, 1 H), 6.40 (dd, J = 1.2, 14.1 Hz, 1
H), 6.07 (dt, J = 1.8, 11.1 Hz, 1 H), 5.86 (d, J = 15.9 Hz, 1 H), 5.78
(dd, J = 5.1, 15.9 Hz, 1 H), 4.95 (dt, J = 5.1, 9.6 Hz, 1 H), 4.40
(quint, J = 6.0 Hz, 1 H), 3.65 (m, 1 H), 2.88 (d, J = 6.6 Hz, 1 H),
2.73 (J = 2.4 Hz, 1 H), 2.44 (m, 2 H), 1.31 (s, 3 H), 0.95 (t, J = 7.8
Hz, 9 H), 0.59 (q, J = 7.8 Hz, 6 H).
FTIR (film): 3437, 1714, 1382, 1243, 1056 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.89 (ddd, J = 3.5, 5.3, 9.9 Hz, 1
H), 6.42 (t, J = 7.5 Hz, 1 H), 6.29–6.32 (m, 1 H), 6.06 (dt, J = 2.1,
9.9 Hz, 1 H), 5.88 (d, J = 15.9 Hz, 1 H), 5.78 (dd, J = 5.1, 15.8 Hz,
1 H), 4.96 (dt, J = 5.1, 9.6 Hz, 1 H), 4.53–4.66 (br m, 1 H), 3.67 (dt,
J = 2.9, 10.5 Hz, 1 H), 2.90 (br s, 1 H), 2.79 (s, 1 H), 2.47–2.41 (m,
2 H), 1.72 (dd, J = 7.8, 13.5 Hz, 1 H), 1.57 (ddd, J = 6.5, 7.8, 10.8
13C NMR (75 MHz, CDCl3): d = 163.8, 148.1, 144.5, 143.5, 137.8,
127.9, 121.8, 77.3, 75.1, 77.3, 72.3, 36.0, 29.6, 20.5, 7.1, 6.7.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2944
S. Shibahara et al.
PAPER
MS (FAB, NBA): m/z = 531 [M + Na+].
MS (FAB, NBA): m/z = 645 [M + Na+].
(6R)-6-[(1E,3R,4R,6S,7E)-4,6-Dihydroxy-8-iodo-3-methyl-3-
[(triethylsilyl)oxy]octa-1,7-dien-1-yl}-5,6-dihydro-2H-pyran-2-
one (28)
(6R)-6-{(1E,3R,4R,6R,7Z,9Z,11E)-6-{[tert-Butyl(dimethyl)si-
lyl]oxy}-13-{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-3-meth-
yl-3-[(triethylsilyl)oxy]trideca-1,7,9,11-tetraen-1-yl}-5,6-
dihydro-2H-pyran-2-one (31)
To an-ice-cooled soln of 29 (37 mg, 0.060 mmol) and stannane 3026
(135 mg, 0.238 mmol) in DMF (0.3 mL) was added
[Pd(MeCN)2Cl2] (0.8 mg, 0.003 mmol), and the mixture was stirred
at 0 °C for 24 h. Sat. aq NaHCO3 (5 mL) was added and the mixture
was extracted with Et2O. The extracts were dried and concentrated
to give a residue that was purified by preparative TLC (10%
EtOAc–benzene) to give 31 as a pale yellow oil; yield: 43 mg
(88%); [a]D24 –0.38 (c 1.04, CDCl3).
Compound 28, a colorless oil, was obtained by reduction of the hy-
droxy ketone with NaBH4/Et3B in the same manner as described for
26
the preparation of 26 from 24; yield: 99%; [a]D +75.6 (c 0.36,
CHCl3).
FTIR (film): 3438, 1711, 1250 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.90 (ddd, J = 3.3, 5.1, 9.6 Hz, 1
H), 6.53 (dd, J = 5.4, 14.1 Hz, 1 H), 6.40 (dd, J = 1.2, 14.1 Hz, 1 H),
6.07 (ddd, J = 1.2, 2.4, 9.9 Hz, 1 H), 5.86 (d, J = 15.9 Hz, 1 H), 5.57
(dd, J = 5.1, 15.9 Hz, 1 H), 4.96 (dt, J = 5.1, 9.6 Hz, 1 H), 4.56 (br
s, 1 H), 3.71 (s, 1 H), 3.59 (d, J = 11.1 Hz, 1 H), 3.01 (br s, 1 H),
2.45 (m, 2 H), 1.62 (br s, 1 H), 1.25–1.47 (m, 1 H), 1.31 (s, 3 H),
0.94 (t, J = 7.5 Hz, 9 H), 0.59 (q, J = 7.5 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 163.7, 147.6, 144.4, 137.4, 128.1,
121.8, 78.7, 77.4, 77.2, 74.7, 37.0, 29.6, 20.48, 7.1, 6.7.
MS (FAB, NBA): m/z = 531 [(M + Na)+].
FTIR (film): 3484, 2949, 1726, 1379, 1248, 1072 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.71 (dd, J = 2.1, 8.1 Hz, 4 H),
7.38–7.41 (m, 6 H), 6.88 (dt, J = 4.5, 9.6 Hz, 1 H), 6.77 (dd,
J = 11.7, 14.7 Hz, 1 H), 6.34 (d, J = 11.1 Hz, 1 H), 6.15 (d, J = 11.1
Hz, 1 H), 6.06 (dt, J = 1.5, 9.6 Hz, 1 H), 5.94 (dd, J = 10.2, 15.9 Hz,
1 H) 5.89 (d, J = 15.9 Hz, 1 H), 5.79 (dd, J = 5.7, 15.9 Hz, 1 H),
5.76–5.84 (m, 1 H), 5.53 (dd, J = 9.9, 10.8 Hz, 1 H), 5.01–4.90 (m,
1 H), 4.96 (dt, J = 6.0, 8.4 Hz, 1 H), 4.29 (d, J = 3.9 Hz, 2 H), 3.69
(d, J = 10.8 Hz, 1 H), 3.04 (d, J = 2.1 Hz, 1 H), 2.43–2.47 (m, 2 H),
1.64 (dt, J = 6.9, 14.1 Hz, 1 H), 1.32 (s, 3 H), 1.26–1.37 (m, 1 H),
1.07 (s, 9 H), 0.92 (t, J = 8.1 Hz, 9 H), 0.88 (s, 9 H), 0.57 (q, J = 8.1
Hz, 6 H), 0.07 (s, 3 H), 0.04 (s, 3 H).
(6R)-6-[(1E,3R,4R,6R,7Z)-6-{[tert-Butyl(dimethyl)silyl]oxy}-4-
hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]octa-1,7-dien-1-
yl]-5,6-dihydro-2H-pyran-2-one (29)
TBDMSOTf (20 mL, 0.087 mmol) was added to a soln of dienediol
25 (38 mg, 0.074 mmol, 84% de) and 2,6-lutidine (12 mL, 0.103
mmol) in CH2Cl2 (0.7 mL) at –78 °C, and the mixture was stirred at
–78 °C for 10 min. The reaction was then quenched with sat. aq
NaHCO3 (5 mL), and the mixture was extracted with CH2Cl2. The
extracts were dried and concentrated to give a residue that was pu-
rified by preparative TLC (EtOAc–benzene, 1:9) to gave 29 [yield:
37 mg (81%)] and its (6S)-isomer [yield: 3 mg (7%)] both as yellow
oils.
13C NMR (75 MHz, CDCl3): d = 164.0, 144.5, 138.0, 135.6, 134.4,
133.6, 130.1, 127.8, 126.8, 124.5, 123.2, 122.3, 121.8, 77.6, 77.2,
75.0, 67.1, 64.2, 39.9, 29.7, 26.9, 25.9, 22.3 19.3, 18.1, 7.1, 6.8,
–4.3, –5.0.
MS (FAB, NBA): m/z = 839 [M + Na+].
Diallyl (1R,3R,4Z,6Z,8E)-3-{[tert-Butyl(dimethyl)silyl]oxy}-10-
{[tert-butyl(diphenyl)silyl]oxy}-1-{(1R)-1-methyl-3-[(2R)-6-
oxo-3,6-dihydro-2H-pyran-2-yl]-1-[(triethylsilyl)oxy]allyl}de-
ca-4,6,8-trien-1-yl Phosphate (32)
Compound 29: [a]D24 +35.9 (c 1.13, CHCl3).
FTIR (film): 3500, 1726, 1462, 1382, 1249, 1081 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.89 (dt, J = 9.9, 4.2 Hz, 1 H), 6.33
(t, J = 7.5 Hz, 1 H), 6.21 (dd, J = 1.2, 7.5 Hz, 1 H), 6.05 (dt, J = 1.5,
9.9 Hz, 1 H), 5.90 (dd, J = 0.9, 15.9 Hz, 1 H), 5.79 (dd, J = 5.7, 15.9
Hz, 1 H), 4.95 (ddt, J = 0.9, 9.0, 5.7 Hz, 1 H), 4.65 (dt, J = 1.2, 6.6
Hz, 1 H), 3.62 (ddd, J = 1.5, 2.7, 10.8 Hz, 1 H), 3.03 (d, J = 2.7 Hz,
1 H), 2.46–2.43 (m, 2 H), 1.70 (ddd, J = 1.5, 7.5, 14.1 Hz, 1 H), 1.38
(ddd, J = 3.3, 10.8, 14.1 Hz, 1 H), 1.33 (s, 3 H), 0.93 (t, J = 8.1 Hz,
9 H), 0.87 (s, 9 H), 0.57 (q, J = 8.1 Hz, 6 H), 0.10 (s, 3 H), 0.05 (s,
3 H).
(CH2=CHCH2O)2PN(i-Pr)2 (105 mg, 0.428 mmol) was added to an
ice-cooled soln of enol 31 (43 mg, 0.052 mmol) and tetrazole (58
mg, 0.830 mmol) in CH2Cl2 (0.8 mL), and the mixture was stirred
stirring for 1.5 h at 0 °C. A 3.04 M soln of t-BuOOH in CH2Cl2 (140
mL, 0.426 mmol) was added, and the mixture was stirred at 0 °C for
1.5 h. The reaction was then quenched with 10% aq Na2S2O3 (1
mL). The mixture was stirred at r.t. for 30 min., diluted with sat. aq
NaHCO3 (5 mL), and extracted with CH2Cl2. The extracts were
dried and concentrated, and the residue was purified by preparative
TLC (hexane–EtOAc, 2:1) to give 32 as a pale yellow oil; yield: 46
mg (89%); [a]D24 +18.8 (c 1.00, CHCl3).
13C NMR (75 MHz, CDCl3): d = 164.0, 144.6, 144.1, 137.9, 126.8,
121.8, 84.9, 80.0, 77.7, 74.9, 74.2, 37.0, 29.7, 25.8, 22.5, 18.1, 7.2,
6.8, –4.3, –5.0.
FTIR (film): 1729, 1504, 1248, 1016 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 7.8 Hz, 4 H), 7.39 (q,
J = 7.3 Hz, 6 H), 6.87 (dq, J = 4.5, 9.3 Hz, 1 H), 6.75 (dd, J = 10.8,
14.7 Hz, 1 H), 6.31 (t, J = 10.2 Hz, 1 H), 6.23 (d, J = 10.2 Hz, 1 H),
6.04 (dd, J = 2.2, 9.9 Hz, 1 H), 5.87 (d, J = 15.6 Hz, 1 H), 5.98–5.78
(m, 5 H), 5.79 (dd, J = 5.1, 15.6 Hz, 1 H), 5.41 (dd, J = 1.5, 3.6 Hz,
1 H), 5.35 (dd, J = 1.5, 3.6 Hz, 2 H), 5.26 (ddd, J = 1.5, 4.5, 10.8 Hz,
1 H), 4.91–4.98 (m, 1 H), 4.94 (dt, J = 5.7, 9.3 Hz, 1 H), 4.52–4.58
(m, 4 H), 4.44 (t, J = 8.2 Hz, 1 H), 4.28 (d, J = 4.5 Hz, 2 H), 2.42–
2.48 (m, 2 H), 1.96 (t, J = 14.4 Hz, 1 H), 1.43 (s, 3 H), 1.19–1.33
(m, 1 H), 1.07 (s, 9 H), 0.95 (t, J = 7.8 Hz, 9 H), 0.88 (s, 9 H), 0.61
(q, J = 7.8 Hz, 6 H), 0.11 (s, 3 H), 0.03 (s, 3 H).
MS (FAB, NBA): m/z = 645 [M + Na+].
25
26
(6S)-Isomer: [a]D –8.0 (c 0.25, CHCl3); [a]D 0.80 (c 0.25,
EtOH).
IR (film): 3523, 1726, 1248, 1078 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.89 (dt, J = 9.9, 3.9 Hz, 1 H), 6.24
(d, J = 7.8 Hz, 1 H), 6.19 (t, J = 7.8 Hz, 1 H), 6.05 (dt, J = 1.8, 9.9
Hz, 1 H), 5.91 (dd, J = 1.3, 16.2 Hz, 1 H), 5.80 (dd, J = 6.0, 16.2 Hz,
1 H), 4.95 (br q, J = 6.9 Hz, 1 H), 4.58 (dt, J = 4.8, 7.8 Hz, 1 H), 3.55
(br d, J = 10.2 Hz, 1 H), 3.17 (d, J = 1.5 Hz, 1 H), 2.45 (m, 2 H),
1.80 (dd, J = 5.4, 14.4 Hz, 1 H), 1.38 (s, 3 H), 1.25–1.43 (m, 1 H),
0.96 (t, J = 7.8 Hz, 9 H), 0.89 (s, 9 H), 0.61 (q, J = 7.8 Hz, 6 H), 0.14
(s, 3 H), 0.08 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.1, 144.7, 136.8, 136.3, 135.6,
134.2, 133.6, 132.7 (JC-P = 5.9 Hz), 129.9, 129.8, 127.8, 127.0,
124.6, 123.7, 122.4, 123.4, 122.4, 121.7, 118.4, 118.2, 82.6 (JC-P
=
13C NMR (75 MHz, CDCl3): d = 164.2, 144.6, 144.0, 137.7, 126.4,
121.8, 80.5, 77.7, 77.3, 73.2, 37.4, 29.8, 25.9, 23.7, 18.0, 7.3, 6.9,
–4.0, –4.7.
6.8 MHz), 77.6, 77.3, 76.1 (JC-P = 4.5 MHz), 68.16 (JC-P = 2.5
MHz), 68.23 (JC-P = 2.6 MHz), 65.1, 64.6, 40.4, 29.7, 26.9, 26.4,
26.0, 24.9, 19.3, 18.1, 7.2, 6.8, –3.9, –4.4.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2945
MS (FAB, NBA): m/z = 999 [M + Na+].
stirred at –78 °C for a further 40 min. Et3N (200 mL, 1.4 mol) was
added and the mixture was stirred at 0 °C for 20 min. The mixture
was neutralized with 5 M HCl (110 mL) and extracted with Et2O.
The extracts were washed with H2O and brine, dried, and concen-
trated to give the corresponding aldehyde as a yellow oil that was
used without purification in the next reaction; yield 35 g.
1H NMR (400 MHz, CDCl3): d = 9.79 (t, J = 1.8 Hz, 1 H), 7.25 (d,
J = 8.8 Hz, 2 H), 6.88 (d, J = 8.8 Hz, 2 H), 4.46 (s, 2 H), 3.81 (s, 3
H), 3.79 (t, J = 6.3 Hz, 2 H), 2.68 (td, J = 6.3 Hz, 1.8 Hz, 2 H).
(+)-Fostriecin (1)
Pd(PPh3)4 (1.6 mg, 0.0014 mmol), HCONH2 (3 mg, 0.044 mmol),
and PPh3 (1 mg, 0.004 mmol) in THF (1 mL) were added to a de-
gassed soln of diallyl phosphate 32 (14 mg, 0.014 mmol), and the
mixture was stirred at r.t. for 4 h. MeOH (0.5 mL) and ion-exchange
resin (Dowex 50WX8-200, 85.4 mg prewashed with THF and
MeOH) were added and the mixture was stirred at r.t. for 20 min.
The mixture was then filtered through Celite and concentrated. The
crude product was dissolved in pyridine (25 mL), and a 1:2:20 mix-
ture of 47% HF, H2O, and MeCN (0.5 mL) was added with cooling
in an ice bath. The mixture was stirred at r.t. for 2 h then aq NaHCO3
(0.5 mL) was added with cooling in an ice-bath. The mixture was
washed with Et2O (1 mL ꢀ 3), and the aqueous layer was concen-
trated by lyophilization. Purification of the residue by reversed-
phase column chromatography [Cosmosil 140C18-PREP (Nacalai
Tesque Co. Inc.; 0.5 g), H2O to MeCN–H2O, 1:9] gave (+)-fostrie-
cin (1) as a white powder; yield: 5 mg (79%); [a]D26 +27.6 (c 0.50,
0.1 M sodium phosphate buffer).
1H NMR (500 MHz, D2O): d = 7.10 (ddd, J = 3.0, 5.5, 10.0 Hz, 1
H), 6.76 (ddd, J = 0.5, 11.0, 15.0 Hz, 1 H), 6.56 (t, J = 11.5 Hz, 1
H), 6.35 (t, J = 11.5 Hz, 1 H), 6.15 (t, J = 11.0 Hz, 1 H), 6.01 (ddd,
J = 1.5, 2.5, 10.0 Hz, 1 H), 5.90–5.96 (m, 3 H), 5.54 (t, J = 9.5 Hz,
1 H), 5.10 (m, 1 H), 4.92 (t, J = 10.0 Hz, 1 H), 4.16 (d, J = 6.0 Hz,
2 H), 4.14 (dt, J = 2.0, 10.0 Hz, 1 H), 2.60 (dddd, J = 1.0, 4.5, 5.5,
18.5 Hz, 1 H), 2.51 (ddt, J = 10.5, 18.5, 3.0 Hz, 1 H), 1.68 (t,
J = 13.0 Hz, 1 H), 1.54 (ddd, J = 2.5, 11.0, 14.0 Hz, 1 H), 1.29 (s, 3
H).
(EtO)2P(O)CO2Et (72 mL, 0.36 mol) was added to a stirred soln of
NaH (60% oil dispersion, 29 g, 0.72 mol) in THF (450 mL) at 0 °C,
and the mixture was stirred at r.t. for 1 h. The mixture was cooled to
0 °C, I2 (119 g, 0.47 mol) was added, and the mixture stirred in dark-
ness at r.t. for 1 h. This mixture was again cooled to 0 °C and a soln
of the aldehyde (35 g) in THF (150 mL) was added. The mixture
was stirred in darkness at r.t. for 1.5 h and then the reaction was
quenched with sat. aq NH4Cl (120 mL). The mixture was extracted
with Et2O and the extracts were washed with sat. aq Na2S2O3 and
brine then dried, concentrated, and purified by chromatography [sil-
ica gel (700 g), hexane–EtOAc, 20:1 to 10:1) to give iodopen-
tenoate 34 as a yellow oil; yield: 47 g [67% (two steps); 4:1 Z/E
mixture]
FTIR (film): 1723, 1613, 1514, 1463, 1363, 1264, 1116, 1042 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.30 (t, J = 6.6 Hz, 4/5 H), 7.26
(d, J = 8.5 Hz, 2 H), 7.00 (t, J = 7.0 Hz, 1/5 H), 6.88 (d, J = 8.5 Hz,
2 H), 4.47 (s, 2 ꢀ 4/5 H), 4.44 (s, 2 ꢀ 1/5 H), 4.26 (q, J = 7.0 Hz,
2 ꢀ 4/5 H), 4.23 (q, J = 7.0 Hz, 2 ꢀ 1/5 H), 3.60 (t, J = 6.6 Hz,
2 ꢀ 4/5 H), 3.52 (t, J = 7.0 Hz, 2 ꢀ 1/5 H), 2.77 (q, J = 7.0 Hz,
2 ꢀ 1/5 H), 2.59 (q, J = 6.6 Hz, 2 ꢀ 4/5 H), 1.33 (t, J = 7.0 Hz,
3 ꢀ 4/5 H), 1.31 (t, J = 7.0 Hz, 3 ꢀ 1/5 H).
13C NMR (100 MHz, CDCl3): d = 162.7, 159.2, 153.0, 150.0, 130.0,
129.3, 113.8, 96.7, 72.7, 72.6, 67.9, 67.1, 62.6, 62.2, 55.3, 37.7,
33.8, 14.2, 14.1.
13C NMR (125 MHz, D2O): d = 170.8, 152.0, 140.6, 136.8, 136.3,
133.4, 129.8, 129.1, 127.1, 127.0, 122.3, 81.8, 79.9, 78.2, 66.6,
65.0, 41.7, 31.9, 24.1.
HRMS (FAB, NBA): m/z = 453 [M + Na+], 476 [M + 2Na+].
UV/Vis (MeOH): lmax 268 nm, with inflections at 259 and 278 nm.
HRMS (EI): m/z calcd for C15H19IO4: 390.0338; found: 390.0322.
The spectral data were identical to those for natural fostriecin ob-
tained from a sample (supplied by Dr. Schultz) by purification using
the exactly same procedure as described for the synthetic fostriecin;
(2Z)-2-Iodo-5-[(4-methoxybenzyl)oxy]pent-2-enal (35)
A 1.02 M soln of DIBAL-H in hexane (285 mL, 0.29 mol) was add-
ed to a soln of enoate 34 (47 g, 0.12 mol) in CH2Cl2 (400 mL) at
–78 °C, and the mixture was stirred at –78 °C for 1 h. The reaction
was quenched with sat. aq Rochelle’s salt (200 mL), and the mixture
was diluted with Et2O and filtered through Celite. The filtrate was
washed with H2O and brine, dried, and concentrated to give the cor-
responding alcohol (42 g) as a pale yellow oil (4:1 Z/E mixture) that
was used without purification in the next reaction.
1H NMR (400 MHz, CDCl3): d = 7.26 (d, J = 8.8 Hz, 2 H), 6.88 (d,
J = 8.8 Hz, 2 H), 6.34 (t, J = 5.7 Hz, 1/5 H), 6.00 (t, J = 6.6Hz, 4/5
H), 4.45 (s, 2 H), 4.24 (d, J = 5.5 Hz, 2 H), 3.81 (s, 3 H), 3.53 (t,
J = 6.6 Hz, 2 ꢀ 4/5 H), 3.45 (t, J = 5.7 Hz, 2 ꢀ 1/5 H), 2.19–2.50 (m,
2 H), 2.05 (t, J = 5.5 Hz, 1 H).
[a]D26 +28.3 (c 0.60, 0.1 M sodium phosphate buffer) {Lit.1c [a]D
26
+33 (c 1.0, 0.1 M sodium phosphate buffer)}.
3-[(4-Methoxybenzyl)oxy]propan-1-ol
Powdered KOH (34 g, 0.60 mol) and 4-methoxybenzyl chloride (41
mL, 0.30 mol) were added to a stirred soln of propane-1,3-diol (44
mL) in DMSO (200 mL) at r.t. After 2.5 h, 5 M HCl (120 mL) was
carefully added with cooling in an ice bath, and the mixture was ex-
tracted with Et2O. The extracts were washed with H2O and brine,
dried, concentrated, and purified by chromatography [silica gel,
(800 g), hexane–EtOAc, 5:2 to 3:2) to a pale yellow oil; yield: 54 g
(92%).
FTIR (film): 3400, 1612, 1514, 1463, 1248, 1176, 1089 cm–1.
PhI(OAc)2 (77 g, 0.24 mol) and TEMPO (1.9 g, 0.012 mol) were
added to a stirred soln of the crude alcohol (42 g) in CH2Cl2 (130
mL) at 0 °C, and the mixture was stirred in darkness at r.t. for 3 h.
The mixture was then diluted with Et2O, washed with sat. aq
Na2S2O3, H2O, and brine then concentrated. Purification of the res-
idue by column chromatography [silica gel (800 g), hexane–
EtOAc, 10:1 to 5:1] gave 35 as an yellow oil; yield: 33 g (79% for
two steps; 20:1 Z/E mixture)
1H NMR (400 MHz, CDCl3): d = 7.25 (d, J = 8.2 Hz, 2 H), 6.88 (d,
J = 8.2 Hz, 2 H), 4.45 (s, 2 H), 3.80 (s, 3 H), 3.77 (t, J = 5.8 Hz, 2
H), 3.63 (t, J = 5.8 Hz, 2 H), 2.35 (br s, 1 H), 1.85 (quint, J = 5.8
Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 159.2, 130.1, 129.2, 113.8, 72.8,
69.0, 61.8, 55.2, 32.0.
HRMS (EI): m/z calcd for C11H18O3: 196.1170; found: 196.1182.
FTIR (film): 1693, 1609, 1513, 1361, 1249, 1176, 1096, 1034, cm–1.
Ethyl 2-Iodo-5-[(4-methoxybenzyl)oxy]pent-2-enoate (34)
A soln of DMSO (51 mL, 0.72 mmol) in CH2Cl2 (150 mL) was add-
ed to a stirred soln of oxalyl chloride (31 mL, 0.36 mol) in CH2Cl2
(300 mL) at –78 °C, and the mixture was stirred at –78 °C for 40
min. A soln of 3-[(4-methoxybenzyl)oxy]propan-1-ol (36 g, 0.18
mol) in CH2Cl2 (150 mL) was then added and the mixture was
1H NMR (400 MHz, CDCl3): d = 9.08 (s, 1/20 H), 8.66 (s, 19/20 H),
7.55 (t, J = 8.3 Hz, 1/20 H), 7.22–7.33 (m, 59/20 H), 6.89 (d,
J = 7.3 Hz, 2 H), 4.48 (s, 2 ꢀ 19/20 H), 4.46 (s, 2 ꢀ 1/20 H), 3.81 (s,
3 H), 3.67 (t, J = 6.1 Hz, 2 ꢀ 19/20 H), 3.58 (t, J = 5.9 Hz, 2 ꢀ 1/20
H), 2.92–2.97 (m, 2 ꢀ 1/20 H), 2.80 (q, J = 6.1 Hz, 2 ꢀ 19/20 H).
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2946
S. Shibahara et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 187.8, 184.5, 159.6, 159.4, 159.3,
157.9, 129.8, 129.7, 129.4, 129.3, 113.9, 112.8, 76.7, 72.8, 67.3,
66.8, 55.3, 53.4, 37.2, 32.4.
(s, 2 H), 3.81 (s, 3 H), 3.61 (t, J = 6.3 Hz, 2 H), 2.68 (dt, J = 6.6, 6.3
Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 192.2, 159.3, 153.5, 148.7, 134.9,
HRMS (EI): calcd for C13H15IO3: 346.0092; found: 346.0052.
130.0, 129.3, 113.8, 104.0, 72.7, 67.3, 55.3, 37.8.
HRMS (EI): m/z calcd [M+] for C15H17IO3: 372.0222; found:
372.0231.
Ethyl (2E,4Z)-4-Iodo-7-[(4-methoxybenzyl)oxy]hepta-2,4-di-
enoate (36)
Ph3P=CHCO2Et (60 g, 171 mmol) was added to a soln of 35 (33 g,
95 mmol) in THF (480 mL) at 0 °C, and the mixture was stirred in
darkness at r.t. for 2 h. Half the THF was evaporated and the mixture
was diluted with hexane, filtered through Celite, and concentrated.
The residue was purified by chromatography [silica gel (800 g),
hexane–EtOAc, 10:1 to 5:1] to give 36 as a pale reddish oil; yield:
40 g (quant).
(3S,4S,5E,7Z)-3-Ethyl-7-iodo-10-[(4-methoxybenzyl)oxy]deca-
1,5,7-trien-4-ol (38)
(2Z)-Pent-2-ene (17 mL, 153 mmol) and a 2.77 M soln of BuLi in
hexane (37 mL, 102 mmol) were added to a stirred suspension of t-
BuOK (11 g, 102 mmol) in THF (100 mL) at –78 °C, and the mix-
ture was stirred at –50 °C for 10 min. The mixture was then cooled
to –78 °C and a soln of (+)-B-methoxy(diisopinocampheyl)borane
(40 g, 128 mmol) in Et2O (80 mL), BF3·Et2O (32 mL, 255 mmol),
and dienal 33 (19 g, 51 mmol) were added sequentially. The mixture
was stirred in darkness at –78 °C for 9 h then 3 M aq NaOH (160
mL) and 30% H2O2 (160 mL) were added, and the mixture was
stirred in darkness at 0 °C for 6 h. The mixture was then filtered
through Celite and extracted with Et2O. The extracts were washed
with H2O and brine, dried, and concentrated. Purification of the res-
idue by flash column chromatography [silica gel (800 g), hexane–
EtOAc, 30:1 to 6:1] gave 38 as a pale yellow oil; yield: 18 g (82%);
[a]D25 +26.9 (c 1.00, CHCl3).
FTIR (film): 1719, 1627, 1514, 1463, 1364, 1303, 1038 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.25 (d, J = 8.8 Hz, 2 H), 7.00 (d,
J = 14.2 Hz, 1 H), 6.90 (d, J = 8.8 Hz, 2 H), 6.41 (t, J = 6.8 Hz, 1
H), 6.12 (d, J = 14.2 Hz, 1 H), 4.46 (s, 2 H), 4.22 (q, J = 7.3 Hz, 2
H), 3.81 (s, 3 H), 3.58 (t, J = 6.8 Hz, 2 H), 2.64 (q, J = 6.8 Hz, 2 H),
1.31 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 159.3, 146.4, 146.1, 130.1,
129.3, 125.3, 113.8, 104.5, 72.7, 67.5, 60.6, 55.3, 37.6, 14.3.
HRMS (FAB): m/z [M+] calcd for C17H21IO4: 416.0485; found:
416.0506.
FTIR (film): 3446, 1606, 1512, 1456, 1246, 1092, 1034 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.26 (d, J = 8.8 Hz, 2 H), 6.88 (d,
J = 8.8 Hz, 2 H), 6.01–5.90 (m, 3 H), 5.57 (dt, J = 17.0, 9.8 Hz, 1
H), 5.19 (dd, J = 10.2, 2.0 Hz, 1 H), 5.14 (dd, J = 17.1, 2.0 Hz, 1
H), 4.45 (s, 2 H), 4.24 (br s, 1 H), 3.80 (s, 3 H), 3.54 (t, J = 6.3 Hz,
2 H), 2.59 (dt, J = 6.3, 6.9 Hz, 2 H), 2.19–2.14 (m, 1 H), 1.58–1.52
(m, 1 H), 1.34–1.26 (m, 1 H), 0.90 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 137.9, 137.1, 132.6, 130.2,
129.2, 118.4, 113.7, 107.5, 73.6, 72.5, 67.9, 55.2, 52.6, 37.1, 23.1,
11.8.
(2E,4Z)-4-Iodo-7-[(4-methoxybenzyl)oxy]hepta-2,4-dien-1-ol
(37)
A 1.02 M soln of DIBAL-H in hexane (216 mL, 220 mmol) was
added to a soln of dienoate 36 (34 g, 82 mmol) in CH2Cl2 (460 mL)
at –78 °C, and the mixture was stirred in darkness at –78 °C for 1 h.
The reaction was quenched with sat. aq Rochelle’s salt (200 mL),
and the mixture was diluted with Et2O and filtered through Celite.
The filtrate was washed with H2O and brine, dried, and concentrated
to give a residue that was purified by chromatography [silica gel
(600 g), hexane–EtOAc, 5:1 to 3:1] to give 37 as a pale yellow oil;
yield: 30 g (98%).
HRMS (EI): m/z calcd for C20H27IO3: 442.1005; found: 442.0965.
FTIR (film): 3417, 1614, 1516, 1254, 1174, 1103 cm–1.
tert-Butyl [(3E,4E,6S,7S)-7-Ethyl-6-hydroxy-3-{3-[(4-methoxy-
benzyl)oxy]propylidene}nona-4,8-dien-1-yl]carbamate (39)
A 0.5 M soln of 9-BBN in THF (7.9 mL, 3.94 mmol) was added to
a soln of tert-butyl vinylcarbamate34 (845 mg, 5.91 mmol) in 1,4-di-
oxane (20 mL) at 10 °C, and the mixture was stirred at r.t. for 9 h.
The mixture was then cooled to 10 °C, and 3 M aq NaOH (7.9 mL)
was added. The resulting mixture was added to a mixture of trienol
38 (870 mg, 1.97 mmol) and [PdCl2(dppf)] (73 mg, 0.10 mmol) in
1,4-dioxane (20 mL) at 10 °C, and the mixture was stirred in dark-
ness at r.t. for 7 h. Most of the 1,4-dioxane was evaporated and the
residue was extracted with Et2O. The extracts were washed with
brine, dried, and concentrated. The residue was purified by chroma-
tography [silica gel (30 g), hexane–EtOAc, 6:1 to 3:1] to give 39 as
a pale yellow oil; yield: 816 mg (90%); [a]D25 +4.9 (c 0.98, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.26 (d, J = 8.6 Hz, 2 H), 6.88 (d,
J = 8.6 Hz, 2 H), 6.09 (dt, J = 14.4, 5.5 Hz, 1 H), 5.99 (t, J = 6.3
Hz, 1 H), 5.97 (d, J = 14.4 Hz, 1 H), 4.45 (s, 2 H), 4.29 (t, J = 5.5
Hz, 2 H), 3.81 (s, 3 H), 3.54 (t, J = 6.3 Hz, 2 H), 2.60 (q, J = 6.3 Hz,
2 H), 1.50 (t, J = 5.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 137.3, 135.8, 132.3, 130.1,
129.3, 128.1, 113.8, 107.3, 72.5, 68.0, 62.1, 55.3, 37.1.
HRMS (EI): m/z calcd for C15H19IO3: 374.0379; found: 374.0364.
(2E,4Z)-4-Iodo-7-[(4-Methoxybenzyl)oxy]hepta-2,4-dienal (33)
A soln of DMSO (2.87 mL, 40.4 mmol) in CH2Cl2 (10 mL) was
added to stirred soln of oxalyl chloride (1.76 mL, 20.2 mmol) in
CH2Cl2 (71 mL) at –78 °C, and the mixture was stirred at –78 °C for
40 min. A soln of 37 (3.78 g, 10.1 mmol) in CH2Cl2 (30 mL) was
then added, and the mixture was stirred in darkness at –78 °C for 70
min. Et3N (11.3 mL, 80.8 mmol) was added, and the mixture was
stirred in darkness at 0 °C for 20 min, then neutralized with 1 M HCl
(100 mL) and extracted with Et2O. The extracts were washed with
H2O and brine, dried, and concentrated. Purification of the residue
by column chromatography [silica gel (38 g), hexane–EtOAc, 4:1]
gave 33 as a pale yellow oil; yield: 3.14 g (84%).
FTIR (film): 3371, 1699, 1516, 1458, 1363, 1250, 1173, 1093 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.24 (d, J = 8.3 Hz, 2 H), 6.87 (d,
J = 8.3 Hz, 2 H), 6.13 (d, J = 15.6 Hz, 1 H), 5.65–5.50 (m, 3 H),
5.15 (d, J = 10.3 Hz, 1 H), 5.10 (d, J = 17.6 Hz, 1 H), 4.90–4.80 (br
s, 1 H), 4.46 (s, 2 H), 4.10–4.00 (br s, 1 H), 3.80 (s, 3 H), 3.47 (t,
J = 6.4 Hz, 2 H), 3.21–3.10 (br s, 2 H), 2.50–2.30 (m, 4 H), 2.15–
2.00 (m, 1 H), 2.00–1.88 (br s, 1 H), 1.87–1.78 (br s, 1 H), 1.60–1.45
(m, 1 H), 1.42 (s, 9 H), 1.30–1.15 (m, 1 H), 0.88 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 155.9, 138.3, 135.7, 134.2,
131.2, 130.3, 129.2, 127.5, 117.9, 113.7, 75.0, 72.5, 68.9, 55.2,
52.7, 39.2, 29.0, 28.4, 28.2, 27.0, 23.3, 11.8.
FTIR (film): 1678, 1610, 1512, 1456, 1244, 1092, 1030 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.71 (d, J = 7.6 Hz, 1 H), 7.26 (d,
J = 8.6 Hz, 2 H), 6.89 (d, J = 8.6 Hz, 2 H), 6.83 (d, J = 14.6 Hz, 1
H), 6.55 (t, J = 6.6 Hz, 1 H), 6.41 (dd, J = 14.6, 7.6 Hz, 1 H), 4.47
HRMS (EI): m/z calcd for C27H41NO5: 459.2984; found: 459.2973.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2947
(3S,4S,5E,7E)-7-{2-[(tert-Butoxycarbonyl)amino]ethyl}-3-eth-
yl-10-[(4-methoxybenzyl)oxy]deca-1,5,7-trien-4-yl Acrylate
(40)
on recovered starting material)] as a colorless viscous oil, and re-
covered 17 (130 mg, 7%) as a pale yellow oil. The enantiomeric pu-
rities of 42 and the recovered 41 were determined to be 100% ee and
59% ee, respectively, by means of 1H NMR (500 MHz) analysis of
the corresponding (R)- and (S)-MTPA esters.
Acryloyl chloride (2.2 mL, 26 mmol) was added to an ice-cooled
soln of 39 (6.0 g, 13 mmol) and DIPEA (4.9 mL, 29 mmol) in
CH2Cl2 (130 mL), and the mixture was stirred stirring at 0 °C for 1
h. The mixture was then poured into sat. aq NaHCO3 (100 mL), ex-
tracted with CH2Cl2, dried, and concentrated. Purification of the res-
idue by column chromatography [Florisil (180 g), hexane–
EtOAc, 20:1 to 10:1] gave 40 as a yellow oil; yield 6.6 g (99%);
[a]D24 +17.5 (c 0.53, CHCl3).
Compound 42
[a]D26 +83.2 (c 1.00, CHCl3).
FTIR (film): 3417, 1730, 1612, 1520, 1260, 1180 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.23 (d, J = 8.5 Hz, 2 H), 6.95 (dd,
J = 9.8, 5.4 Hz, 1 H), 6.88 (d, J = 8.5 Hz, 2 H), 6.04 (d, J = 9.8 Hz,
1 H), 5.91–5.89 (m, 2 H), 5.10–4.95 (m, 2 H), 4.44 (s, 2 H), 3.80 (s,
3 H), 3.70–3.60 (m, 3 H), 3.48–3.40 (m, 1 H), 3.30–3.09 (m, 2 H),
3.09 (s, 1 H), 2.44–2.40 (m, 1 H), 1.86–1.65 (m, 4 H), 1.65–1.54 (m,
1 H), 1.43 (s, 9 H), 1.59–1.39 (m, 1 H), 0.94 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.0, 159.2, 156.1, 150.1, 135.7,
129.6, 129.2, 125.0, 120.6, 113.7, 100.5, 79.9, 79.0, 76.5, 72.8,
68.8, 55.1, 39.1, 36.0, 35.3, 30.5, 28.3, 21.4, 10.9.
FTIR (film): 3359, 1712, 1616, 1512, 1400, 1252, 1180, 1093 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.25 (d, J = 8.5 Hz, 2 H), 6.87 (d,
J = 8.5 Hz, 2 H), 6.40 (dd, J = 17.3, 1.5 Hz, 1 H), 6.17 (d, J = 15.1
Hz, 1 H), 6.15 (dd, J = 17.3, 10.3 Hz, 1 H), 5.81 (dd, J = 10.3, 1.5
Hz, 1 H), 5.63–5.53 (m, 3 H), 5.33 (t, J = 7.3 Hz, 1 H), 5.12 (dd,
J = 10.4, 1.8 Hz, 1 H), 5.05 (dd, J = 17.3, 1.8 Hz, 1 H), 4.92–4.84
(br s, 1 H), 4.46 (s, 2 H), 3.80 (s, 3 H), 3.46 (t, J = 6.3 Hz, 2 H),
3.21–3.02 (br s, 2 H), 2.45–2.40 (m, 4 H), 2.31–2.20 (m, 1 H), 1.57–
1.49 (m, 1 H), 1.42 (s, 9 H), 1.31–1.23 (m, 1 H), 0.88 (t, J = 7.4 Hz,
3 H).
HRMS (EI): m/z calcd for C28H41NO8: 519.2833; found: 519.2841.
6,7-(OH)2-Isomer
[a]D20 +76.0 (c 0.80, CHCl3).
FTIR (film): 3367, 1707, 1514, 1456, 1375, 1248, 1169, 1066 cm–1.
13C NMR (75 MHz, CDCl3): d = 165.2, 159.0, 155.7, 137.4, 137.3,
136.4, 132.4, 130.5, 130.3, 129.2, 128.7, 123.1, 117.4, 113.7, 78.9,
77.2, 72.5, 68.8, 55.2, 50.0, 39.2, 29.1, 28.5, 28.4, 23.2, 11.6.
1H NMR (400 MHz, CDCl3): d = 7.26 (d, J = 8.5 Hz, 2 H), 7.12 (dd,
J = 9.6 Hz, 6.6 Hz, 1 H), 6.88 (d, J = 8.5 Hz, 2 H), 6.04 (d, J = 9.6
Hz, 1 H), 5.70 (t, J = 7.4 Hz, 1 H), 4.89–4.75 (m, 1 H), 4.52 (d,
J = 3.3 Hz, 1 H), 4.49 (d, J = 3.3 Hz, 1 H), 4.45 (s, 2 H), 4.41 (d,
J = 4.1 Hz, 1 H), 3.81 (s, 3 H), 3.75 (t, J = 7.4 Hz, 1 H), 3.66–3.57
(m, 1 H), 3.47 (t, J = 7.1 Hz, 2 H), 3.41–3.19 (m, 2 H), 2.62–2.53
(m, 1 H), 2.48–2.36 (m, 3 H), 2.32–2.18 (m, 1 H), 1.90–1.74 (m, 1
H), 1.40 (s, 9 H), 1.59–1.38 (m, 1 H), 0.97 (t, J = 7.4 Hz, 3 H).
HRMS (EI): m/z calcd for C30H43NO6: 513.3091; found: 513.3079.
tert-Butyl {(3E)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-
2H-pyran-2-yl]vinyl}-6-[(4-methoxybenzyl)oxy]hex-3-en-1-
yl}carbamate (41)
Grubbs second-generation catalyst (1.01 g, 1.19 mmol) was added
to a degassed soln of acrylate 40 (6.09, 11.9 mmol) in CH2Cl2 (1187
mL), and the mixture was refluxed for 11 h. The mixture was then
washed with sat. aq NaHCO3, dried, and concentrated. The residue
was purified by chromatography [silica gel (200 g), hexane–
EtOAc 4:1–2:1] to give 41 as a pale yellow oil; yield: 4.41 g (77%);
[a]D24 +68.7 (c 0.69, CHCl3). The optical purity was determined to
be 93% ee by HPLC (Chiralcel AD, Daicel, hexane–i-PrOH, 8:1).
13C NMR (75 MHz, CDCl3): d = 164.3, 159.1, 157.0, 151.7, 137.8,
130.2, 129.3, 126.6, 120.6, 113.7, 79.6, 78.3, 72.6, 72.3, 69.9, 62.2,
55.2, 39.6, 35.7, 29.0, 28.6, 28.3, 20.4, 10.9.
HRMS (EI): m/z calcd for C28H41NO8: 519.2832; found: 519.2822.
FTIR (film): 3361, 1716, 1614, 1512, 1373, 1248, 1171, 1097 cm–1.
Allyl [(3R,4R)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-2H-
pyran-2-yl]vinyl}-3,4,6-trihydroxyhexyl]carbamate (43)
1H NMR (400 MHz, CDCl3): d = 7.25 (d, J = 8.3 Hz, 2 H), 6.97 (dd,
J = 9.8, 5.4 Hz, 1 H), 6.88 (d, J = 8.3 Hz, 2 H), 6.32 (d, J = 16.1
Hz, 1 H), 6.05 (dd, J = 10.2, 1.4 Hz, 1 H), 5.73–5.65 (m, 2 H), 5.02
(t, J = 4.4 Hz, 1 H), 4.93–4.84 (br s, 1 H), 4.47 (s, 2 H), 3.81 (s, 3
H), 3.48 (t, J = 6.3 Hz, 2 H), 3.22–3.06 (br m, 2 H), 2.52–2.35 (m,
5 H), 1.68–1.55 (m, 1 H), 1.52–1.44 (m, 1 H), 1.42 (s, 9 H), 0.96 (t,
J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 163.9, 159.0, 155.7, 150.0, 139.9,
136.3, 135.1, 133.1, 130.2, 129.1, 120.8, 120.6, 113.6, 80.1, 72.4,
68.7, 55.1, 39.5, 39.1, 28.9, 28.2, 26.9, 21.4, 10.9.
To an ice-cooled soln of diol 42 (720 mg, 1.39 mmol) in THF (9.8
mL) was treated with 5 M HCl (4.2 mL), and the mixture was stirred
at r.t. for 2.5 days. The mixture was then cooled to 0 °C and
NaHCO3 (2.0 g, 28.8 mmol) and allyl chloroformate (0.3 mL, 2.78
mmol) were added. The mixture was stirred at r.t. for 3 h, then di-
luted with sat. aq NaHCO3 (10 mL) and extracted with EtOAc. The
extracts were dried and concentrated, and the residue was purified
by column chromatography [silica gel (22 g), EtOAc] to give 43 as
24
an amorphous solid; yield: 520 mg (98%); [a]D +90.6 (c 0.53,
CHCl3).
HRMS (EI): m/z calcd for C28H39NO6: 485.2778; found: 485.2769.
FTIR (film): 3390, 1714, 1533, 1385, 1257, 1061 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.96 (dd, J = 9.8 Hz, 5.4 Hz, 1 H),
6.05 (d, J = 9.8 Hz, 1 H), 5.97–5.89 (m, 3 H), 5.30 (d, J = 17.1 Hz,
1 H), 5.20 (d, J = 10.5 Hz, 1 H), 5.28–5.19 (br s, 1 H), 5.08–5.01 (m,
1 H), 4.56 (d, J = 5.6 Hz, 2 H), 3.95–3.80 (m, 2 H), 3.75–3.65 (m, 1
H), 3.58–3.43 (m, 1 H), 3.38–3.28 (m, 2 H), 3.28–3.14 (m, 2 H),
2.49–2.41 (m, 1 H), 2.45–2.27 (m, 1 H), 1.97–1.84 (m, 1 H), 1.80–
1.63 (m, 3 H), 1.55–1.40 (m, 1 H), 0.96 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 164.3, 156.5, 150.4, 135.3, 132.7,
125.0, 120.3, 117.4, 80.1, 75.8, 74.6, 65.4, 60.5, 39.1, 36.6, 35.3,
32.7, 21.5, 11.0.
Dihydroxylation of Carbamate 41
Super AD-mix2 prepared by mixing K3Fe(CN)6 (4.0 g, 12.3 mmol),
K2CO3 (1.7 g, 12.3 mmol), (DHQD)2PHAL (320 mg, 0.41 mmol),
K2OsO2(OH)4 (15 mg, 0.041 mmol), and MeSO2NH2 (800 mg, 8.2
mmol), was added to an ice-cooled soln of 41 (2.0 g, 4.1 mmol) in
1:1 t-BuOH–H2O (40 mL). The mixture was stirred at 0 °C for 10 h,
sat. aq Na2S2O3 (40 mL) was added, and the mixture was stirred for
another 40 min at r.t. The mixture was then extracted with EtOAc,
and the extracts were washed with brine, dried, and concentrated.
Purification of the residue by column chromatography [silica gel
(60 g), hexane–EtOAc 2:1–1:4] gave diol 42 [yield: 1.26 g (59%,
63% based on recovered starting material)] as a colorless amor-
phous solid, the 6,7-(OH)2-isomer [yield: 180 mg (9%, 10% based
HRMS (EI): m/z calcd for C19H29NO7: 383.1944; found: 383.1930.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2948
S. Shibahara et al.
PAPER
Allyl {(3R,4R)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-2H-
pyran-2-yl]vinyl}-3,4,6-tris[(triethylsilyl)oxy]hexyl}carbamate
(44)
Less-Polar Epimer of 46
[a]D26 +46.9 (c 0.75, CHCl3).
FTIR (film): 3408, 1714, 1520, 1456, 1244, 1103, 1007 cm–1.
TESOTf (2.1 mL, 9.1 mmol) was added to a soln of triol 43 (500
mg, 1.3 mmol) and 2,6-lutidine (1.5 mL, 13 mmol) in CH2Cl2 (13
mL) at –78 °C, and the mixture was stirred at –78 °C for 3 h. The
reaction was quenched with brine (15 mL), and the mixture was
stirred at r.t. for a further 10 h. The mixture was then extracted with
Et2O and the extracts were washed with brine then dried and con-
centrated. Purification of the residue by column chromatography
[silica gel (25 g), hexane–EtOAc, 10:1 to 5:1] gave 44 as a colorless
oil; yield: 700 mg (74%); [a]D23 +52.2 (c 0.65, CHCl3).
1H NMR (400 MHz, CDCl3): d = 6.95 (dd, J = 9.8, 4.9 Hz, 1 H),
6.06 (d, J = 9.8 Hz, 1 H), 5.96–5.85 (m, 2 H), 5.83 (dd, J = 15.6, 5.6
Hz, 1 H), 5.29 (d, J = 17.5 Hz, 1 H), 5.19 (d, J = 10.2 Hz, 1 H), 5.04
(t, J = 5.6 Hz, 1 H), 5.00–4.91 (br s, 1 H), 4.64–4.50 (m, 2 H), 4.49–
4.39 (br, 1 H), 3.85 (d, J = 7.8 Hz, 1 H), 3.31–3.11 (m, 2 H), 2.48–
2.39 (m, 2 H), 2.18–2.10 (br, 1 H), 2.08–1.96 (m, 2 H), 1.92–1.70
(m, 1 H), 1.70–1.44 (m, 3 H), 0.99–0.84 (m, 21 H), 0.72–0.58 (m,
12 H).
13C NMR (100 MHz, CDCl3): d = 163.7, 155.9, 149.5, 136.3, 132.9,
125.1, 120.8, 117.3, 85.2, 80.2, 79.6, 74.6, 72.4, 65.3, 58.6, 41.0,
39.5, 37.4, 36.5, 21.6, 11.1, 7.2, 7.0, 6.9, 5.4.
FTIR (film): 3350, 1727, 1520, 1461, 1382, 1244, 1104, 1011 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.93 (dd, J = 9.8, 5.1 Hz, 1 H),
6.05 (d, J = 9.8 Hz, 1 H), 5.97–5.74 (m, 3 H), 5.29 (d, J = 17.3 Hz,
1 H), 5.19 (d, J = 10.2 Hz, 1 H), 5.03–5.00 (m, 1 H), 4.96–4.82 (br
s, 1 H), 4.55 (d, J = 4.9 Hz, 2 H), 3.77–3.52 (m, 3 H), 3.38–3.06 (m,
2 H), 2.46–2.38 (m, 1 H), 2.08–1.99 (m, 1 H), 1.92–1.70 (m, 2 H),
1.70–1.48 (m, 2 H), 1.38–1.24 (m, 1 H), 1.00–0.87 (m, 30 H), 0.72–
0.50 (m, 18 H).
13C NMR (100 MHz, CDCl3): d = 163.6, 155.8, 149.5, 136.5, 132.8,
124.4, 120.7, 117.0, 80.3, 79.8, 75.0, 65.1, 59.4, 39.5, 37.6, 36.5,
35.6, 21.5, 10.9, 7.1, 7.0, 6.8, 6.7, 5.4, 4.3.
HRMS (EI): m/z calcd for C33H57NO7Si2: 635.3673; found:
635.3672.
More-Polar Epimer of 46
[a]D26 +27.3 (c 0.81, CHCl3).
FTIR (film): 3305, 1712, 1522, 1456, 1242, 1107, 1009 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.94 (dd, J = 9.8, 5.4 Hz, 1 H),
6.06 (d, J = 9.8 Hz, 1 H), 5.98–5.85 (m, 2 H), 5.82 (dd, J = 15.6, 5.6
Hz, 1 H), 5.30 (d, J = 17.0 Hz, 1 H), 5.20 (d, J = 10.7 Hz, 1 H), 5.03
(t, J = 5.6 Hz, 1 H), 5.03–4.94 (br s, 1 H), 4.62–4.50 (m, 2 H), 4.49–
4.40 (m, 1 H), 3.79 (d, J = 6.4 Hz, 1 H), 3.36–3.10 (m, 2 H), 2.53
(s, 1 H), 2.50–2.40 (m, 1 H), 2.08–1.90 (m, 2 H), 1.90–1.74 (m, 2
H), 1.74–1.58 (m, 2 H), 1.55–1.44 (m, 1 H), 1.00–0.88 (m, 21 H),
0.72–0.64 (m, 12 H).
HRMS (FAB): m/z [M + Na+] calcd for C37H71NO7Si3Na:
748.4439; found: 748.4422.
Allyl {(3R,4R)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-2H-
pyran-2-yl]vinyl}-6-oxo-3,4-bis[(triethylsilyl)oxy]hexyl}car-
bamate (45)
13C NMR (100 MHz, CDCl3): d = 163.7, 156.0, 149.5, 136.2, 132.9,
125.2, 120.8, 117.3, 84.6, 80.2, 79.7, 75.6, 74.1, 65.4, 60.5, 41.0,
39.4, 37.4, 36.6, 21.7, 11.1, 7.2, 7.1, 6.9, 5.5.
DMSO (1.11 mL, 15.6 mmol) and a soln of carbamate 44 (1.29 g,
1.78 mmol) in CH2Cl2 (8 mL) were added to a stirred soln of oxalyl
chloride (0.68 mL, 7.82 mmol) in CH2Cl2 (4.9 mL) at –78 °C, and
the mixture was stirred at –78 °C for 20 min and then at –40 °C for
20 min. The mixture was cooled to –78 °C, Et3N (3.72 mL, 26.7
mmol) was added, and the mixture was stirred at 0 °C for 20 min.
The mixture was then diluted with Et2O, washed with 1 M HCl,
H2O, and sat. aq NaHCO3, then dried and concentrated. Purification
of the residue by column chromatography [Florisil (20 g), hexane–
EtOAc, 5:1] gave 45 as a pale yellow oil; yield: 909 mg (84%);
[a]D25 +24.8 (c 0.75, CHCl3).
HRMS (EI): m/z calcd for C33H57NO7Si2: 635.3673; found:
635.3669.
Allyl {(3R,4R)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-2H-
pyran-2-yl]vinyl}-6-oxo-3,4-bis[(triethylsilyl)oxy]oct-7-yn-1-
yl}carbamate (47)
Alcohol 46 (698 mg, 1.10 mmol) was oxidized by using Dess–
Martin periodinane (1.42 g, 3.29 mmol) and NaHCO3 (924 mg, 11.0
mmol) in the same manner as described for the preparation of 21
from 20. Purification by column chromatography [silica gel (24 g),
hexane–EtOAc, 5:1] gave 47 as a colorless oil; yield: 666 mg
(96%); [a]D26 +38.6 (c 1.00, CHCl3).
FTIR (film): 3346, 1718, 1525, 1460, 1242, 1107, 1005 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.77 (s, 1 H), 6.95 (dd, J = 9.8, 5.4
Hz, 1 H), 6.06 (d, J = 9.8 Hz, 1 H), 5.98–5.89 (m, 2 H), 5.83 (dd,
J = 15.6, 5.2 Hz, 1 H), 5.30 (d, J = 17.1 Hz, 1 H), 5.20 (d, J = 10.2
Hz, 1 H), 5.03 (t, J = 5.2 Hz, 1 H), 4.88–4.75 (br s, 1 H), 4.65–4.55
(m, 2 H), 4.15 (t, J = 3.9 Hz, 1 H), 3.41–3.07 (m, 2 H), 2.64 (dd,
J = 18.0, 3.9 Hz, 1 H), 2.49–2.37 (m, 2 H), 2.15–2.05 (m, 1 H),
1.85–1.71 (m, 1 H), 1.65–1.45 (m, 2 H), 1.10–0.80 (m, 21 H), 0.64
(q, J = 7.5 Hz, 6 H), 0.62 (q, J = 7.5 Hz, 6 H).
FTIR (film): 3350, 1720, 1523, 1460, 1242, 1105, 1009 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.95 (dd, J = 9.8, 5.4 Hz, 1 H),
6.07 (d, J = 9.8 Hz, 1 H), 5.97–5.85 (m, 2 H), 5.82 (dd, J = 15.6, 5.9
Hz, 1 H), 5.30 (d, J = 17.3 Hz, 1 H), 5.20 (d, J = 10.2 Hz, 1 H), 5.06
(t, J = 5.9 Hz, 1 H), 4.84–4.75 (br s, 1 H), 4.62–4.45 (m, 2 H), 4.25
(d, J = 5.8 Hz, 1 H), 3.26 (s, 1 H), 3.35–3.11 (m, 2 H), 2.88 (dd,
J = 17.6, 2.5 Hz, 1 H), 2.54 (dd, J = 17.6, 5.8 Hz, 1 H), 2.49–2.40
(m, 1 H), 2.13–2.05 (m, 1 H), 1.82–1.70 (m, 1 H), 1.70–1.45 (m, 2
H), 1.01–0.92 (m, 21 H), 0.71–0.56 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 200.7, 163.8, 156.0, 149.7, 135.3,
133.0, 125.9, 121.0, 117.5, 80.1, 79.8, 73.0, 65.5, 47.7, 39.5, 37.8,
36.8, 21.8, 11.2, 7.3, 7.1, 6.9, 5.2.
HRMS (EI): m/z calcd for C31H55NO7Si2: 609.3517; found:
13C NMR (100 MHz, CDCl3): d = 185.1, 163.7, 156.0, 149.5, 135.3,
133.0, 125.5, 120.9, 117.5, 81.7, 80.1, 79.5, 79.1, 73.0, 65.5, 49.9,
39.6, 37.6, 36.7, 21.8, 11.2, 7.3, 7.1, 6.9, 5.2.
609.3515.
Ethynylation of Aldehyde 45
Aldehyde 45 (909 mg, 1.49 mmol) was subjected to ethynylation by
using anhyd CeCl3 (1.07 g, 4.33 mmol) and a 1.07 M soln of ethy-
nylmagnesium bromide in THF (4.0 mL, 4.33 mmol), in the same
manner as described for the preparation of 20 from 19. Purification
by column chromatography [silica gel (50 g), hexane–EtOAc, 5:1 to
2:1] gave 46, a colorless oil, as an epimeric mixture; yield: 698 mg
(74%; 11R/11S = 1:1).
HRMS (EI): m/z calcd for C33H55NO7Si2: 633.3517; found:
633.3509.
Allyl {(3R,4R,7Z)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-
2H-pyran-2-yl]vinyl}-8-iodo-6-oxo-3,4-bis[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (48)
Ynone 47 (339 mg, 0.521 mmol) was subjected to Z-selective hy-
droiodination by using AcOH (31 mL, 0.546 mmol) and NaI (156
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2949
mg, 1.04 mmol) in acetone (0.52 mL) in darkness at r.t. for 7 days,
in the same manner as described for the preparation of 22 from 21.
Purification by flash column chromatography [silica gel (15 g),
hexane–t-BuOMe, 3:1] gave 48 [yield: 360 mg (90%)] and 49
[yield: 30 mg (8%)], each as a yellow oil.
J = 18.5 Hz, 1 H), 5.20 (d, J = 10.2 Hz, 1 H), 5.03 (t, J = 5.3 Hz, 1
H), 5.12–4.96 (br s, 1 H), 4.70–4.45 (m, 2 H), 4.08 (d, J = 7.8 Hz,
1 H), 3.20–3.04 (m, 2 H), 2.82 (d, J = 17.1 Hz, 1 H), 2.56 (dd,
J = 17.1, 9.8 Hz, 1 H), 2.50–2.35 (m, 1 H), 2.07–1.88 (m, 2 H), 1.70
(d, J = 9.3 Hz, 1 H), 1.70–1.40 (m, 2 H), 0.96 (t, J = 7.8 Hz, 12 H),
0.65 (q, J = 7.8 Hz, 6 H).
Compound 48
[a]D24 +68.2 (c 1.05, CHCl3).
FTIR (film): 3349, 1722, 1569, 1460, 1243, 1103, 1009 cm–1.
13C NMR (100 MHz, CDCl3): d = 198.8, 163.5, 156.1, 149.6, 135.3,
135.0, 132.9, 126.1, 120.8, 117.4, 92.1, 79.9, 78.6, 72.8, 65.4, 45.8,
39.4, 36.5, 36.5, 21.7, 11.1, 7.3, 6.9.
1H NMR (400 MHz, CDCl3): d = 7.31 (d, J = 8.8 Hz, 1 H), 7.17 (d,
J = 8.8 Hz, 1 H), 6.95 (dd, J = 9.8, 5.3 Hz, 1 H), 6.07 (d, J = 9.8 Hz,
1 H), 5.98–5.87 (m, 2 H), 5.81 (dd, J = 15.6, 5.4 Hz, 1 H), 5.29 (d,
J = 17.1 Hz, 1 H), 5.20 (d, J = 10.3 Hz, 1 H), 5.06 (t, J = 5.4 Hz, 1
H), 4.89–4.76 (br s, 1 H), 4.62–4.49 (m, 2 H), 4.30 (d, J = 6.3 Hz,
1 H), 3.35–3.08 (m, 2 H), 2.82 (dd, J = 18.0, 1.5 Hz, 1 H), 2.49 (dd,
J = 18.0, 7.8 Hz, 1 H), 2.52–2.40 (m, 1 H), 2.14–2.04 (m, 1 H),
1.81–1.71 (m, 1 H), 1.71–1.58 (m, 1 H), 1.58–1.45 (m, 1 H), 1.00–
0.90 (m, 21 H), 0.68–0.53 (m, 12 H).
HRMS (EI): m/z calcd for C27H42INO7Si: 647.1775; found:
647.1783.
Allyl {(3R,4R,6R,7Z)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihy-
dro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-8-iodo-3-[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (51)
Hydroxy ketone 50 (64 mg, 0.099 mmol) was subjected to anti-se-
lective reduction using Me4NBH(OAc)3 (313 mg, 1.19 mmol) and
AcOH (0.37 mL) in MeCN (5.0 mL) at –10 °C for 3 h, in the same
manner as described for the preparation of 25 from 24. Purification
by column chromatography [silica gel (2 g), CH2Cl2–MeOH, 40:1
to 30:1] gave 51 as a colorless oil; yield: 62 mg (96%); [a]D21 +43.7
(c 0.90, CHCl3).
13C NMR (100 MHz, CDCl3): d = 196.7, 163.6, 155.9, 149.4, 135.6,
135.3, 132.9, 125.0, 120.9, 117.3, 90.8, 80.0, 79.5, 73.0, 65.3, 48.4,
39.4, 37.5, 36.7, 21.7, 11.1, 7.2, 7.0, 6.8, 5.1.
HRMS (EI): m/z calcd for C33H56INO7Si2: 761.2640; found:
761.2624.
FTIR (film): 3373, 1711, 1527, 1412, 1248, 1090 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.96 (dd, J = 9.7, 5.3 Hz, 1 H),
6.41 (t, J = 7.5 Hz, 1 H), 6.31 (d, J = 7.5 Hz, 1 H), 6.05 (d, J = 9.7
Hz, 1 H), 5.97–5.88 (m, 2 H), 5.82 (dd, J = 15.6, 5.2 Hz, 1 H), 5.29
(d, J = 18.5 Hz, 1 H), 5.20 (d, J = 10.3 Hz, 1 H), 5.33–5.15 (br s, 1
H), 5.02 (t, J = 5.2 Hz, 1 H), 4.75–4.48 (m, 3 H), 3.92–3.75 (m, 1
H), 3.50–3.12 (m, 4 H), 2.53–2.38 (m, 1 H), 2.05–1.82 (m, 2 H),
1.82–1.70 (m, 1 H), 1.70–1.40 (m, 3 H), 1.05–0.94 (m, 12 H), 0.64
(q, J = 7.8 Hz, 6 H).
Allyl {(3R,4R,7E)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-
2H-pyran-2-yl]vinyl}-8-iodo-6-oxo-3,4-bis[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (49)
Ynone 47 (10 mg, 0.015 mmol) was subjected to E-selective hy-
droiodination by using AcOH (0.1 mL) and NaI (5.2 mg, 0.035
mmol) in acetone (0.15 mL) in darkness at r.t. for 3 h, in the same
manner as described for the preparation of 23 from 21. Purification
by preparative TLC (hexane–t-BuOMe, 1:1) gave 49 as a yellow
oil; yield: 9.5 mg (79%); [a]D24 +68.2 (c 1.05, CHCl3).
13C NMR (100 MHz, CDCl3): d = 163.6, 156.3, 149.6, 143.0, 135.9,
132.8, 126.0, 120.8, 117.4, 81.4, 80.1, 79.9, 73.5, 72.6, 65.4, 39.4,
36.6, 36.0, 35.7, 21.7, 11.1, 7.2, 6.9.
FTIR (film): 3359, 1716, 1566, 1244, 1101, 1001 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.80 (d, J = 14.9 Hz, 1 H), 7.13
(d, J = 14.9 Hz, 1 H), 6.96 (dd, J = 9.8, 4.8 Hz, 1 H), 6.08 (d,
J = 9.8 Hz, 1 H), 5.97–5.87 (m, 2 H), 5.82 (dd, J = 15.6, 5.2 Hz, 1
H), 5.30 (d, J = 17.1 Hz, 1 H), 5.20 (d, J = 10.2 Hz, 1 H), 5.08 (t,
J = 5.2 Hz, 1 H), 4.84–4.77 (br s, 1 H), 4.62–4.50 (m, 2 H), 4.23 (d,
J = 7.3 Hz, 1 H), 3.35–3.08 (m, 2 H), 2.70 (d, J = 16.5 Hz, 1 H),
2.52–2.40 (m, 2 H), 2.20–2.00 (m, 1 H), 1.80–1.70 (m, 1 H), 1.70–
1.45 (m, 2 H), 1.00–0.88 (m, 21 H), 0.68–0.52 (m, 12 H).
HRMS (EI): m/z calcd for C27H44INO7Si: 649.1932; found:
649.1944.
Allyl {(3R,4R,6S,7Z)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihy-
dro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-8-iodo-3-[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (52)
Hydroxy ketone 50 (20 mg, 0.030 mmol) was subjected to syn-se-
lective reduction by using NaBH4 (2 mg, 0.045 mmol) and Et3B (1.0
M in THF, 45 mL, 0.045 mmol) in THF (0.6 mL) and MeOH (0.1
mL) at –78 °C for 14 h, in the same manner as described for the
preparation of 26 from 24. Purification by preparative TLC (hex-
ane–EtOAc, 1:1) gave 52 as a colorless oil; yield: 14 mg (74%);
[a]D21 +44.2 (c 0.6, CHCl3).
13C NMR (100 MHz, CDCl3): d = 195.3, 163.6, 155.9, 149.4, 145.0,
135.4, 132.9, 125.1, 120.9, 117.4, 99.0, 79.9, 79.5, 73.2, 65.4, 44.3,
39.5, 37.6, 36.7, 21.8, 11.2, 7.2, 7.0, 6.8, 5.1.
HRMS (EI): m/z calcd C33H56INO7Si2: 761.2640; found: 761.2631.
FTIR (film): 3346, 1718, 1519, 1460, 1383, 1252, 1090, 1012 cm–1.
Allyl {(3R,4R,7Z)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihydro-
2H-pyran-2-yl]vinyl}-4-hydroxy-8-iodo-6-oxo-3-[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (50)
H2O (0.7 mL) and AcOH (2.1 mL) were added to an ice-cooled soln
of 48 (188 mg, 0.247 mmol) in THF (2.1 mL), and the mixture was
stirred in darkness at r.t. for 2.5 days. The mixture was then diluted
with EtOAc, washed with sat. aq NaHCO3, dried, and concentrated.
The residue was purified by chromatography [silica gel (6 g), hex-
ane–EtOAc, 10:1 to 2:1] to give 50 as a colorless oil; yield: 142 mg
(89%); [a]D24 +43.8 (c 0.73, CHCl3).
1H NMR (400 MHz, CDCl3): d = 6.96 (dd, J = 9.3, 5.2 Hz, 1 H),
6.44–6.26 (m, 2 H), 6.06 (d, J = 9.3 Hz, 1 H), 6.00–5.81 (m, 3 H),
5.30 (d, J = 17.0 Hz, 1 H), 5.20 (d, J = 10.2 Hz, 1 H), 5.28–5.15 (br
s, 1 H), 5.06 (t, J = 3.9 Hz, 1 H), 4.63–4.48 (m, 3 H), 4.30–4.10 (br
s, 1 H), 3.80 (t, J = 5.8 Hz, 1 H), 3.65–3.48 (br s, 1 H), 3.40–3.08
(m, 2 H), 2.52–2.40 (m, 1 H), 1.96–1.74 (m, 4 H), 1.71–1.58 (m, 1
H), 1.58–1.42 (m, 1 H), 0.96 (t, J = 7.8 Hz, 12 H), 0.64 (q, J = 7.8
Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 163.6, 149.6, 148.5, 142.7, 135.5,
132.6, 125.2, 120.6, 117.3, 81.7, 79.6, 77.2, 75.2, 71.5, 65.4, 39.0,
38.8, 36.3, 21.3, 10.7, 6.7, 4.8.
FTIR (film): 3388, 2951, 2877, 1707, 1522, 1458, 1381, 1238,
1078, 735 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40 (d, J = 8.7 Hz, 1 H), 7.26 (d,
J = 8.7 Hz, 1 H), 6.96 (dd, J = 9.7, 5.3 Hz, 1 H), 6.06 (d, J = 9.7 Hz,
1 H), 5.98–5.88 (m, 2 H), 5.84 (dd, J = 15.6, 5.3 Hz, 1 H), 5.30 (d,
HRMS (FAB): m/z [M+] calcd for C27H44NO7SiI: 649.1932; found:
649.1940.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2950
S. Shibahara et al.
PAPER
Allyl {(3R,4R,6R,7E)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihy-
dro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-8-iodo-3-[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (53)
H), 1.70–1.58 (m, 2 H), 1.58–1.45 (m, 1 H), 1.00–0.88 (m, 12 H),
0.66–0.58 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 163.8, 149.9, 149.8, 147.8, 136.0,
132.8, 125.5, 120.9, 117.7, 79.8, 77.2, 76.7, 75.2, 65.8, 39.9, 39.3,
36.5, 36.2, 21.6, 11.0, 6.9, 5.1.
HRMS (FAB): m/z [M+] calcd for C27H44NO7SiI: 649.1932; found:
649.1959.
Compound 49 (100 mg, 0.13 mmol) was subjected to desilylation
using AcOH (1.2 mL) and H2O (0.4 mL) in THF (1.2 mL) at r.t. for
1.5 days, in the same manner as described for the preparation of 50
from 48. Purification by preparative TLC (hexane–EtOAc, 1:1)
gave recovered 49 (41 mg, 41%) and the corresponding hydroxy ke-
tone as a yellow oil; yield: 40 mg (48%, 81% based on recovered
starting material); [a]D21 +88.5 (c 2.0, CHCl3).
Allyl {(3R,4R,6R,7Z,9Z)-10-Cyclohexyl-3-{(E)-2-[(2S,3S)-3-eth-
yl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-3-
[(triethylsilyl)oxy]deca-7,9-dien-1-yl}carbamate (56)
FTIR (film): 3380, 2956, 2877, 1718, 1567, 1460, 1382, 1248, 1083
cm–1.
A soln of stannane 55 (479 mg, 1.17 mmol) in THF (4 mL) and
[Pd(MeCN)2Cl2] (31 mg, 0.117 mmol) were added to a degassed
soln of 51 (250 mg, 0.39 mmol) in MeCN (16 mL) at 0 °C, and the
mixture was stirred at r.t. for 1 h. The mixture was then concentrated
and the residue was purified by chromatography [silica gel (15 g),
hexane–EtOAc, 2:1 to 1:1] to give unreacted 51 (108 mg, 43%) and
56 as a colorless oil; yield: 113 mg (46%, 81% based on residual
starting material); [a]D21 +78.4 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.90 (d, J = 4.8 Hz, 1 H), 7.17 (d,
J = 4.8 Hz, 1 H), 6.97 (dd, J = 9.7, 4.4 Hz, 1 H), 6.07 (d, J = 9.7 Hz,
1 H), 5.98–5.89 (m, 2 H), 5.83 (dd, J = 15.6, 5.4 Hz, 1 H), 5.30 (d,
J = 11.5 Hz, 1 H), 5.21 (d, J = 10.3 Hz, 1 H), 5.16–5.07 (br s, 1 H),
5.03 (t, J = 5.4 Hz, 1 H), 4.66–4.50 (m, 2 H), 4.03 (d, J = 8.8 Hz, 1
H), 3.38–3.20 (m, 2 H), 3.21 (s, 1 H), 2.75 (d, J = 17.1 Hz, 1 H),
2.60–2.40 (m, 3 H), 2.02–1.88 (m, 2 H), 1.64–1.46 (m, 2 H), 1.03–
0.92 (m, 12 H), 0.65 (q, 7.3 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 197.2, 163.7, 156.2, 149.7, 144.6,
135.3, 132.9, 126.2, 120.9, 117.6, 100.5, 85.0, 79.8, 78.5, 72.8,
65.4, 41.7, 39.3, 36.5, 21.6, 11.0, 7.1, 6.7
MS (FAB): m/z (%): 136 (85), 154 (100), 648 [M+].
HRMS (FAB): m/z [(M + 1)+] calcd for C27H43NO7SiI: 648.1854;
FTIR (film): 3385, 1712, 1523, 1451, 1382, 1248, 1083 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.94 (dd, J = 9.7, 5.4 Hz, 1 H),
6.33 (t, J = 11.5 Hz, 1 H), 6.12 (t, J = 11.5 Hz, 1 H), 6.06 (d, J = 9.7
Hz, 1 H), 5.95–5.79 (m, 3 H), 5.45 (t, J = 10.2 Hz, 1 H), 5.39 (t,
J = 10.2 Hz, 1 H), 5.29 (d, J = 17.3 Hz, 1 H), 5.20 (d, J = 10.8 Hz,
1 H), 5.30–5.20 (m, 1 H), 5.01 (t, J = 4.4 Hz, 1 H), 5.00–4.90 (br s,
1 H), 4.55 (m, 2 H), 3.86 (d, J = 9.2 Hz, 1 H), 3.32 (m, 2 H), 3.01
(s, 1 H), 2.45–2.40 (m, 2 H), 2.15–2.10 (br s, 1 H), 1.99–1.83 (m, 2
H), 1.72–1.03 (m, 14 H), 0.97–0.91 (m, 12 H), 0.63 (q, J = 7.8 Hz,
6 H).
13C NMR (100 MHz, CD3OD): d = 166.5, 152.6, 140.3, 137.7,
135.4, 134.6, 129.3, 126.6, 124.5, 122.7, 121.1, 117.4, 82.2, 81.0,
74.3, 66.2, 65.4, 40.7, 40.3, 37.8, 37.7, 34.3, 29.2, 27.9, 27.1, 22.8,
14.0, 11.4, 7.8.
found: 648.1835.
The hydroxy ketone (20 mg, 0.031 mmol) thus obtained was sub-
jected to anti-selective reduction in the same manner as described
for the preparation of 26 from 24. Purification by preparative TLC
(hexane–EtOAc, 1:2) gave 53 as a colorless oil; yield: 17 mg
(85%); [a]D21 +69.5 (c 0.85, CHCl3).
FTIR (film): 3408, 1709, 1526, 1459, 1383, 1249, 1084 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.96 (dd, J = 9.8, 5.4 Hz, 1 H),
6.58 (dd, J = 14.6, 5.3, Hz, 1 H), 6.40 (d, J = 14.6 Hz, 1 H), 6.07 (d,
J = 9.8 Hz, 1 H), 6.05–5.78 (m, 3 H), 5.30 (d, J = 17.1 Hz, 1 H),
5.17 (d, J = 10.2 Hz, 1 H), 5.25–5.10 (br s, 1 H), 5.02 (t, J = 4.8 Hz,
1 H), 4.70–4.51 (br, 2 H), 4.60–4.38 (br, 1 H), 3.92–3.70 (br, 1 H),
3.42–3.22 (br, 2 H), 3.22–3.10 (br s, 1 H), 3.05–2.83 (br s, 1 H),
2.55–2.40 (m, 1 H), 2.11–1.80 (m, 2 H), 1.80–1.40 (m, 4 H), 1.18–
0.85 (m, 12 H), 0.64 (q, J = 7.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 163.7, 156.4, 149.7, 148.1, 136.0,
132.8, 126.4, 120.9, 117.7, 117.6, 80.0, 78.8, 73.5, 72.2, 65.5, 39.3,
36.5, 36.2, 35.7, 21.6, 11.0, 7.1, 6.8.
HRMS (FAB): m/z [M+] calcd for C27H44NO7SiI: 649.1932; found:
649.1939.
HRMS (FAB): m/z [M+] calcd for C35H57NO7Si: 631.3905; found:
631.3895.
Allyl {(3R,4R,6S,7Z,9Z)-10-Cyclohexyl-3-{(E)-2-[(2S,3S)-3-eth-
yl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-3-
[(triethylsilyl)oxy]deca-7,9-dien-1-yl}carbamate (57)
Coupling of 52 (12 mg, 0.018 mmol) with 55 (21 mg, 0.054 mmol)
was carried out by using Pd(MeCN)2Cl2 (1.4 mg, 0.0054 mmol) in
4:1 MeCN–THF (2 mL), in the same manner as described for the
preparation of 56 from 51. Purification by preparative TLC (hex-
ane–EtOAc, 1:1) gave 57 as a yellow oil; yield: 6.5 mg (56%);
[a]D21 +115.5 (c 0.40, CHCl3).
FTIR (film): 3353, 2927, 1716, 1517, 1453, 1247, 1092, 1012 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.95 (dd, J = 9.7, 5.4 Hz, 1 H),
6.33 (t, J = 11.2 Hz, 1 H), 6.10 (t, J = 11.2 Hz, 1 H), 6.06 (d, J = 9.7
Hz, 1 H), 5.96–5.90 (m, 2 H), 5.86 (dd, J = 6.6, 4.9 Hz, 1 H), 5.45
(t, J = 9.8 Hz, 1 H), 5.40 (t, J = 11.2 Hz, 1 H), 5.30 (dd, J = 17.1, 1.5
Hz, 1 H), 5.40–5.30 (br s, 1 H), 5.20 (dd, J = 10.8, 1.5 Hz, 1 H), 5.05
(t, J = 4.9Hz, 1 H), 4.91–4.82 (br, 1 H), 4.55 (d, J = 5.8 Hz, 2 H),
4.18–4.05 (br 1 H), 3.78 (t, J = 4.4 Hz, 1 H), 3.42–3.10 (m, 2 H),
2.99–2.80 (br s, 1 H), 2.51–2.39 (m, 2 H), 1.94–1.56 (m, 9 H),
1.56–1.41 (m, 1 H), 1.35–1.01 (m, 6 H), 0.93 (t, J = 7.8 Hz, 12 H),
0.61 (q, J = 7.8 Hz, 6 H).
13C NMR (100 MHz, CD3OD): d = 166.5, 158.7, 152.6, 140.8,
137.4, 134.6, 126.3, 126.3, 126.0, 122.9, 121.1, 117.3, 82.3, 77.9,
77.0, 66.3, 65.9, 43.0, 40.7, 38.6, 37.7, 37.5, 34.4, 34.2, 27.1, 22.8,
11.3, 7.5, 6.3.
Allyl {(3R,4R,6S,7E)-3-{(E)-2-[(2S,3S)-3-Ethyl-6-oxo-3,6-dihy-
dro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-8-iodo-3-[(triethylsi-
lyl)oxy]oct-7-en-1-yl}carbamate (54)
Syn-selective reduction of the hydroxy ketone prepared from 49 fol-
lowed by purification by preparative TLC (hexane–EtOAc, 1:2)
gave 54 in the same manner as described for the preparation of 26
from 24; yield: 74%; [a]D21 +79.0 (c 0.5, CHCl3).
FTIR (film): 3369, 1715, 1521, 1383, 1247, 1097, 1011 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.96 (dd, J = 9.8, 5.4 Hz, 1 H),
6.54 (dd, J = 14.2, 5.4 Hz, 1 H), 6.38 (d, J = 14.2 Hz, 1 H), 6.06 (d,
J = 9.8 Hz, 1 H), 5.96–5.81 (m, 3 H), 5.30 (dd, J = 17.1, 1.5 Hz, 1
H), 5.21 (dd, J = 10.3, 1.5 Hz, 1 H), 5.25–5.10 (br s, 1 H), 5.04 (t,
J = 4.0 Hz, 1 H), 4.56 (d, J = 5.8 Hz, 2 H), 4.38–4.30 (br s, 1 H),
4.13–3.95 (br s, 1 H), 3.92–3.80 (br s, 1 H), 3.77 (dd, J = 3.7, 6.3
Hz, 1 H), 3.38–3.12 (m, 2 H), 2.47–2.42 (m, 1 H), 1.93–1.70 (m, 3
HRMS (FAB): m/z [M+] calcd for C35H57NO7Si: 631.3905; found:
631.3879.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

PAPER
(+)-Fostriecin and (+)-Phoslactomycin B
2951
Allyl {(3R,4R,6R,7E,9Z)-10-Cyclohexyl-3-{(E)-2-[(2S,3S)-3-eth-
yl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-3-
[(triethylsilyl)oxy]deca-7,9-dien-1-yl}carbamate (58)
Coupling of 53 (17 mg, 0.026 mmol) with 55 (31 mg, 0.078 mmol)
was carried out by using [Pd(MeCN)2Cl2] (2.0 mg, 0.0078 mmol) in
4:1 MeCN–THF (2.5 mL), in the same manner as described for the
preparation of 56 from 51. Purification by preparative TLC (hex-
ane–EtOAc, 1:1) gave recovered 53 (4.4 mg, 26%) and 58 as a yel-
low oil: yield: 7.1 mg (42%); [a]D21 75.0 (c 0.40, CHCl3).
1H NMR (400 MHz, CDCl3): d = 6.93 (dd, J = 9.8, 5.4 Hz, 1 H),
6.22 (t, J = 11.7 Hz, 1 H), 6.05 (d, J = 9.8 Hz, 1 H), 6.02 (t, J = 11.7
Hz, 1 H), 5.95–5.87 (m, 2 H), 5.78 (dd, J = 15.8, 5.0 Hz, 1 H), 5.44
(t, J = 9.8 Hz, 1 H), 5.36 (t, J = 9.8 Hz, 1 H), 5.28 (d, J = 17.1 Hz,
1 H), 5.18 (d, J = 10.3 Hz, 1 H), 5.20–5.17 (m, 1 H), 5.01 (t, J = 5.0
Hz, 1 H), 4.97–4.88 (br, 1 H), 4.62–4.49 (br, 2 H), 3.83 (d, J = 10.7
Hz, 1 H), 3.38 (s, 1 H), 3.31–3.29 (m, 2 H), 2.43–2.38(m, 2 H),
1.95–1.85 (m, 2 H), 1.72–1.62 (m, 7 H), 1.60–1.41 (m, 2 H), 1.31–
1.02 (m, 5 H), 0.97–0.89 (m, 12 H), 0.87 (s, 9 H), 0.61 (q, J = 7.7
Hz, 6 H), 0.06 (s, 3 H), 0.02 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 163.7, 156.2, 149.6, 140.1, 136.1,
133.4, 133.1, 125.5, 123.1, 120.9, 120.8, 117.2, 80.1, 79.0, 73.4,
67.5, 65.3, 39.4, 38.5, 36.5, 36.4, 36.0, 33.1, 33.0, 25.9, 25.8, 25.7,
21.6, 17.9, 11.0, 7.1, 6.8, –4.4, –5.2.
FTIR (film): 3421, 2925, 1717, 1522, 1454, 1246, 1083 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.95 (dd, J = 9.6, 5.4 Hz, 1 H),
6.55 (dd, J = 11.0, 14.8 Hz, 1 H), 6.06 (d, J = 9.6 Hz, 1 H), 5.95–
5.78 (m, 4 H), 5.67 (dd, J = 14.8, 5.8 Hz, 1 H), 5.32–5.25 (m, 2 H),
5.20 (d, J = 10.3 Hz, 1 H), 5.18–5.07 (br s, 1 H), 5.01 (t, J = 4.8 Hz,
1 H), 4.55 (d, J = 4.9 Hz, 2 H), 4.52–4.45 (m, 1 H), 3.91–3.75 (br s,
1 H), 3.40–3.22 (m, 2 H), 3.04–2.95 (br s, 1 H), 2.52–2.40 (m, 2 H),
2.38–2.20 (br s, 1 H), 2.03–1.80 (m, 2 H), 1.74–1.44 (m, 8 H), 1.35–
1.00 (m, 6 H), 0.97 (t, J = 7.3 Hz, 3 H), 0.96 (t, J = 7.8 Hz, 9 H),
0.64 (q, J = 7.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 158.7, 152.6, 138.8, 137.8,
137.7, 134.6, 127.5, 126.6, 126.0, 121.1, 117.3, 82.2, 80.9, 79.5,
74.4, 69.9, 66.2, 40.7, 40.1, 38.1, 37.7, 34.4, 27.1, 27.0, 22.8, 11.4,
7.9, 7.7.
HRMS (FAB): m/z [(M +Na)+] calcd for C41H71NO7Si2Na:
768.4667; found: 768.4669.
Allyl {(3R,4R,6R,7Z,9Z)-4-{[Bis(allyloxy)phosphoryl]oxy}-6-
{[tert-butyl(dimethyl)silyl]oxy}-10-cyclohexyl-3-{(E)-2-
[(2R,3R)-3-ethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-3-
[(triethylsilyl)oxy]deca-7,9-dien-1-yl}carbamate (61)
(CH2=CHO)2PN(i-Pr) (0.26 mL, 1.04 mmol) was added to an ice-
cooled soln of 60 (100 mg, 0.13 mmol) and tetrazole (140 mg, 2.08
mmol) in CH2Cl2 (6.5 mL), and the mixture was stirred at r.t. for 1
h. 30% H2O2 (0.21 mL) was added at 0 °C, and the mixture was
stirred at 0 °C for 2 h. The reaction was quenched with sat. aq
Na2S2O3 (10 mL), and the mixture was extracted with EtOAc. The
extracts were washed with brine, dried, concentrated, and purified
by preparative TLC (hexane–EtOAc, 1:1) to give 61 (111 mg, 94%)
as a colorless oil: [a]D21 +58.3 (C 0.40, CHCl3).
HRMS (FAB): m/z [(M + 1)+] calcd for C35H57NO7Si: 632.3983;
found: 632.4003.
Allyl {(3R,4R,6S,7E,9Z)-10-Cyclohexyl-3-{(E)-2-[(2S,3S)-3-eth-
yl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-4,6-dihydroxy-3-
[(triethylsilyl)oxy]deca-7,9-dien-1-yl}carbamate (59)
Coupling of 54 (10 mg, 0.015 mmol) with 55 (18 mg, 0.045 mmol)
was carried out by using [Pd(MeCN)2Cl2] (1.2 mg, 0.0045 mmol) in
4:1 MeCN–THF (1.5 mL) in the same manner as described for the
preparation of 56 from 51. Purification by preparative TLC (hex-
ane–EtOAc, 1:1) gave recovered 53 (4.4 mg, 26%) and 59 as a yel-
low oil; yield: 4.9 mg (52%); [a]D21 +111.0 (c 0.20, CHCl3).
FTIR (film): 3336, 1724, 1525, 1457, 1252, 1084, 1018 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.93 (dd, J = 9.8, 5.4 Hz, 1 H),
6.18 (t, J = 11.2 Hz, 1 H), 6.09 (t, J = 11.2 Hz, 1 H), 6.04 (d, J = 9.8
Hz, 1 H), 5.98–5.89 (m, 5 H), 5.76 (dd, J = 15.9, 5.6 Hz, 1 H), 5.39–
5.17 (m, 8 H), 5.02–4.95 (br s, 1 H), 4.91 (t, J = 9.5 Hz, 1 H), 4.62
(t, J = 7.3 Hz, 1 H), 4.53 (m, 6 H), 3.45–3.24 (br, 2 H), 2.39–2.27
(m, 2 H), 2.12–1.80 (m, 2 H), 1.69–1.46 (m, 10 H), 1.38–1.08 (m, 4
H), 0.99–0.90 (m, 12 H), 0.87 (s, 9 H), 0.68 (q, J = 7.4 Hz, 6 H),
0.10 (s, 3 H), 0.03 (s, 3 H).
13C NMR (100 MHz, C6D6): d = 162.5, 158.8, 148.5, 141.8, 135.4,
135.0, 133.8, 133.1, 127.2, 123.5, 123.0, 122.2, 121.2, 118.0, 117.7,
116.8, 80.1, 79.6, 78.3, 77.6, 68.3, 65.8, 65.3, 40.8, 39.4, 37.1, 36.8,
36.7, 33.4, 30.0, 26.5, 26.4, 26.2, 21.8, 18.4, 11.0, 7.7, 7.2, –3.7,
–4.0.
FTIR (film): 3370, 2926, 1715, 1519, 1454, 1248, 1101 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.95 (dd, J = 9.7, 5.4 Hz, 1 H),
6.52 (dd, J = 11.0, 15.1 Hz, 1 H), 6.06 (d, J = 9.7 Hz, 1 H), 5.95–
5.80 (m, 4 H), 5.63 (dd, J = 15.1, 6.4 Hz, 1 H), 5.35–5.20 (m, 3 H),
5.20 (d, J = 10.3 Hz, 1 H), 5.07–5.02 (br, 1 H), 4.55 (d, J = 4.8 Hz,
2 H), 4.49–4.40 (br s, 1 H), 3.95–3.80 (br s, 1 H), 3.78–3.70 (br, 1
H), 3.38–3.00 (m, 3 H), 2.50–2.38 (m, 2 H), 1.92–1.40 (m, 12 H),
1.33–1.00 (m, 4 H), 0.95 (t, J = 7.4 Hz, 12 H), 0.61 (q, J = 7.4 Hz,
6 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 158.7, 152.6, 139.5, 137.5,
136.5, 134.6, 128.2, 127.2, 126.3, 121.1, 117.3, 82.3, 77.7, 77.5,
71.1, 66.3, 42.2, 40.7, 38.3, 38.1, 37.5, 34.4, 34.1, 27.0, 22.8, 11.3,
7.5, 6.5.
HRMS (FAB): m/z [(M +Na)+] calcd for C47H80NO10PSi2Na:
928.4956; found: 928.4957.
Desilylation of 61
H2O (0.8 mL), 47% HF (1.6 mL), and pyridine (0.4 mL) were added
to an ice-cooled soln of phosphate 61 (101 mg, 0.11 mmol) in
MeCN (8.0 mL), and the mixture was stirred at r.t. for 2 h. The mix-
ture was then cooled to 0 °C, basified with sat. aq NaHCO3 (10 mL),
and extracted with EtOAc. The extracts were washed with sat. aq
NaHCO3 and brine, dried, concentrated, and purified by preparative
TLC (EtOAc) to give diol 62 (22 mg) and the partially desilylated
11-hydroxy derivative (50 mg). The latter was dissolved in MeCN
(4.9 mL) and desilylated again by treatment with H2O (0.49 mL),
47% HF (0.98 mL), and pyridine (0.25 mL) at r.t. for 2 h. After
work-up, preparative TLC (EtOAc) gave diol 62 (16 mg) and the
11-monohydroxy derivative (10 mg). As a result, diol 62 was ob-
tained as a colorless oil; total yield: 38 mg (51%). Note that expo-
sure of 61 to the desilylation conditions for 3 hours caused
appreciable decomposition of 62. The optimal procedure for obtain-
ing 62 involves a 2-hour reaction of 61, and a further 2-hour reac-
tion of the 11-mono hydroxy deriviative.
HRMS (FAB): m/z [M+] calcd for C35H57NO7Si: 631.3904; found:
631.3876.
Allyl {(3R,4R,6R,7Z,9Z)-10-Cyclohexyl-3-{(E)-2-[(2S,3S)-3-eth-
yl-6-oxo-3,6-dihydro-2H-pyran-2-yl]vinyl}-6-{[tert-butyl(di-
methyl)silyl]oxy}-4-hydroxy-3-[(triethylsilyl)oxy]deca-7,9-
dien-1-yl}carbamate (60)
TBDMSOTf (54 mL, 0.24 mmol) was added to a soln of 56 (100 mg,
0.16 mmol) and 2,6-lutidine (37 mL, 0.32 mmol) in CH2Cl2 (8.0 mL)
at –78 °C, and the mixture was stirred at –78 °C for 40 min. The re-
action was then quenched with sat. aq NaHCO3 (10 mL), and the
mixture was extracted with EtOAc. The extracts were washed with
brine, dried, and concentrated. Purification of the residue by prepar-
ative TLC (CH2Cl2–EtOAc, 15:1) gave 60 as a yellow oil; yield:
113 mg (95%); [a]D21 +57.1 (c 0.35, CHCl3).
FTIR (film): 3450 1725, 1520, 1463, 1382, 1251, 1079 cm–1.
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

2952
S. Shibahara et al.
PAPER
11-Mono Hydroxy Derivative
Colorless oil; [a]D21 +45.5 (C 1.5, MeOH).
FTIR (film): 3415, 1725, 1525, 1455, 1248, 1019 cm–1.
(46 mL) at –78 °C, and stirring was maintained at –78 °C for 30
min. Bu3SnCl (2.26 mL, 8.33 mmol) was added, and the mixture
was stirred at –78 °C for 5 h. The mixture was then diluted with hex-
ane, washed with H2O, dried, and concentrated to give tributyl(2-
cyclohexylethynyl)stannane (3.90 g) as a colorless oil that was used
for the next reaction without purification.
1H NMR (400 MHz, CDCl3): d = 6.92 (dd, J = 9.7, 5.3 Hz, 1 H),
6.26 (t, J = 11.2 Hz, 1 H), 6.14–5.75 (m, 7 H), 5.52–5.25 (m, 7 H),
5.19 (d, J = 10.3 Hz, 1 H), 5.02 (t, J = 4.4 Hz, 1 H), 4.94–4.82 (br s,
1 H), 4.82–4.70 (br s, 1 H), 4.70–4.50 (m, 7 H), 3.95–3.78 (br s, 1
H), 3.40–3.11 (m, 2 H), 2.51–2.35 (m, 2 H), 2.18–2.00 (m, 1 H),
2.00–1.38 (m, 10 H), 1.38–0.85 (m, 17 H), 0.68 (q, J = 7.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 163.7, 156.0, 149.6, 139.9, 134.2,
132.8, 132.1, 132.1, 132.0, 126.2, 123.9, 121.2, 121.0, 118.9, 118.8,
117.4, 80.0, 79.9, 79.8, 68.8, 68.7, 65.3, 62.6, 39.4, 38.2, 37.5, 36.4,
33.1, 33.0, 25.9, 21.6, 11.0, 7.1, 6.7.
1H NMR (400 MHz, CDCl3): d = 2.48–2.39 (m, 1 H), 1.82–1.39 (m,
13 H), 1.39–1.22 (m, 9 H), 0.98–0.84 (m, 15 H).
A soln of crude tributyl(2-cyclohexylethynyl)stannane (1.42 g) in
THF (7.0 mL) was added to a soln of [Cp2ZrHCl] (1.38 g, 5.35
mmol) in THF (10.9 mL), and the mixture was stirred at r.t. for 7 h.
The mixture was then diluted with hexane and stirred at r.t. for 20
min. The resulting precipitates were filtered off and the filtrate was
concentrated. Purification of the residue by column chromatogra-
phy [silica gel (30 g), hexane] gave 55 as a colorless oil; yield: 977
mg (69% for two steps)
HRMS (FAB): m/z [M+] calcd for C41H66NO10PSi: 791.4194;
found: 791.4182.
FTIR (film): 1595, 1452 cm–1.
Allyl {(3R,4R,6R,7Z,9Z)-4-{[Bis(allyloxy)phosphoryl]oxy}-10-
cyclohexyl-3-{(E)-2-[(2S,3S)-3-ethyl-6-oxo-3,6-dihydro-2H-py-
ran-2-yl]vinyl}-3,6-dihydroxydeca-7,9-dien-1-yl}carbamate
(62)
1H NMR (400 MHz, CDCl3): d = 6.32 (dd, J = 12.2, 9.3 Hz, 1 H),
5.66 (d, J = 12.2, 7.3 Hz, 1 H), 1.80–1.39 (m, 11 H), 1.39–1.08 (m,
12 H), 1.00–0.97 (m, 15 H).
13C NMR (100 MHz, CDCl3): d = 154.9, 125.3, 46.9, 33.3, 29.2,
27.4, 25.9, 13.7, 10.4.
Colorless oil; [a]D21 +30.1 (C 0.25, MeOH).
FTIR (film): 3372, 1725, 1522, 1449, 1254, 1022 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.91 (dd, J = 9.8, 5.9 Hz, 1 H),
6.30 (t, J = 11.7 Hz, 1 H), 6.10–5.83 (m, 8 H), 5.44–5.28 (m, 8 H),
5.23 (dd, J = 14.4, 1.4 Hz, 1 H), 5.12–5.00 (br s, 1 H), 4.79 (t,
J = 8.8 Hz, 1 H), 4.62–4.50 (m, 6 H), 4.48 (t, J = 9.8 Hz, 1 H), 4.12–
3.90 (br s, 1 H), 3.42–3.08 (m, 2 H), 2.51–2.38 (m, 2 H), 1.94–1.42
(m, 10 H), 1.34–1.03 (m, 6 H), 0.94 (t, J = 7.8 Hz, 3 H).
13C NMR (100 MHz, CD3OD): d = 166.6, 158.9, 152.9, 141.0,
135.6, 135.0, 134.8, 134.1, 134.1, 134.0, 127.8, 122.8, 121.2, 119.1,
117.6, 83.8, 83.7, 82.1, 76.6, 70.1, 66.5, 64.7, 40.7, 40.2, 38.2, 37.9,
37.4, 34.5, 27.4, 27.1, 23.0, 11.5.
HRMS (EI): m/z calcd for C20H40Sn: 400.2152; found: 400.2166.
Acknowledgment
We thank Dr. Robert J. Schultz of the Drug Synthesis and Chemi-
stry Branch, Developmental Therapeutics Program, Division of
Cancer Treatment and Diagnosis, National Cancer Institute for the
generous supply of natural fostriecin. We also thank Professor Yui-
chi Kobayashi (Tokyo Institute of Technology) for the 1H and 13
C
NMR spectra of phoslactomycin B. This work was partly supported
by Grant-in-Aid for Scientific Research of Japan Society for the
Promotion of Science (JSPS) and The Ministry of Education,
Culture, Sports, Science and Technology (MEXT).
HRMS (FAB): m/z: [(M + Na)+] calcd for C35H52NO10PNa:
700.3227; found: 700.3220.
(+)-Phoslactomycin B (2)
To an ice-cooled soln of 62 (10 mg, 0.015 mmol) in CH2Cl2 (1.5
mL) were added H2O (13 mL), [PdCl2(PPh3)2] (0.5 mg, 0.75 mmol),
and Bu3SnH (15 mL, 0.057 mmol), and the mixture was stirred at
0 °C for 1.5 h. The mixture was concentrated and the residue was
subjected to preparative TLC (MeCN–H2O, 5:2) followed by re-
verse-phase HPLC (J’sphere ODSM-80, MeCN–H2O, 1:2) to give
References
(1) (a) Tunac, J. B.; Graham, B. D.; Dobson, W. E. J. Antibiot.
1983, 36, 1595. (b) Stampwala, S. S.; Bunge, R. H.; Hurley,
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(c) Boger, D. L.; Hikota, M.; Lewis, B. M. J. Org. Chem.
1997, 62, 1748.
22
2 as a colorless powder; yield: 5.6 mg (73%); [a]D +82.0 (c 0.2,
MeOH) [Lit.2c [a]D21 +81 (c 1.0, MeOH)].
FTIR (film): 3209, 1724, 1642, 1450, 1384, 1246, 1105 cm–1.
(2) (a) Fushimi, S.; Nishikawa, S.; Shimizu, A.; Seto, H.
J. Antibiot. 1989, 42, 1019. (b) Fushimi, S.; Furihata, K.;
Seto, H. J. Antibiot. 1989, 42, 1026. (c) Ozasa, T.; Suzuki,
K.; Sasamata, M.; Tanaka, K.; Kobori, M.; Kadota, S.;
Nagai, K.; Saito, T.; Watanabe, S.; Iwanami, M. J. Antibiot.
1989, 42, 1331. (d) Ozasa, T.; Tanaka, K.; Sasamata, M.;
Kaniwa, H.; Shimizu, M.; Matsumoto, H.; Iwanami, M.
J. Antibiot. 1989, 42, 1339. (e) Shibata, T.; Kurihara, S.;
Yoda, K.; Haruyama, H. Tetrahedron 1995, 51, 11999.
(f) Sekiyama, Y.; Palaniappan, N.; Reynolds, K. A.; Osada,
H. Tetrahedron 2003, 59, 7465. (g) Choudhuri, S. D.;
Ayers, S.; Soine, W. H.; Reynolds, K. V. J. Antibiot. 2005,
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Kuroda, M.; Doe, M.; Iio, H.; Tanaka, T. J. Antibiot. 2007,
60, 762.
1H NMR (500 MHz, CD3OD): d = 7.08 (dd, J = 9.6, 5.0, 1 H), 6.14–
6.05 (m, 1 H), 6.23 (d, J = 8.0 Hz, 2 H), 6.01 (dd, J = 9.6, 1.2 Hz, 1
H), 5.91 (d, J = 16.0 Hz, 1 H), 5.41 (t, J = 8.0 Hz, 1 H), 5.31 (t,
J = 8.0 Hz, 1 H), 5.09 (t, J = 4.8 Hz, 1 H), 4.98 (t, J = 9.1 Hz, 1 H),
4.32–4.20 (br, 1 H), 3.15–2.98 (br, 2 H), 2.60–2.40 (m, 2 H), 2.35–
2.18(m, 1 H), 1.78–1.00 (m, 17 H), 0.95 (t, J = 7.5 Hz, 3 H).
13C NMR (100 Hz, CD3OD): d = 166.4, 152.7, 140.2, 137.4, 134.6,
127.5, 124.5, 123.0, 121.0, 82.3, 78.2, 77.9, 64.6, 40.6, 37.6, 37.1,
34.4, 34.3, 27.1, 26.9, 22.7, 11.4.
HRMS (FAB): m/z [(M + Na)+] calcd for C25H40NO8PNa:
536.2389; found: 536.2380.
These spectral data exhibited good agreement with those reported
for the natural specimen.2c
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118.
Tributyl[(Z)-2-cyclohexylvinyl]stannane (55)
A 1.58 M soln of BuLi in hexane (5.9 mL, 9.25 mmol) was added
to a stirred soln of ethynylcyclohexane (1.0 g, 9.25 mmol) in THF
Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York

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Synthesis 2009, No. 17, 2935–2953 © Thieme Stuttgart · New York