Studies on synthesis of the C-1 to C-18 fragment of pamamycins 607 and 621A

Article abstract of DOI:10.1002/cjoc.201090280

Some efforts directed towards synthesis of the C-1 to C-18 fragment of natural antibiotic pamamycins 607 and 621A are disclosed. The nine stereogenic centers in the fragment were installed using a chiral auxiliary-induced asymmetric aldol reaction, a chir

Full text of DOI:10.1002/cjoc.201090280

FULL PAPER
Studies on Synthesis of the C-1 to C-18 Fragment of
Pamamycins 607 and 621A†
Ren, Guobao(任国宝)
Wu, Yikang*(伍贻康)
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
Some efforts directed towards synthesis of the C-1 to C-18 fragment of natural antibiotic pamamycins 607 and
621A are disclosed. The nine stereogenic centers in the fragment were installed using a chiral auxiliary-induced
asymmetric aldol reaction, a chiral building block derived from malic acid, or substrate chirality-induced asymmet-
ric reduction of a ketone carbonyl group.
Keywords aldol reaction, alcohol, antibiotic, cross metathesis, chiron, enantioselective synthesis
Introduction
Results and discussion
Pamamycin 621A (1a) and pamamycin 607 (1b) are
The general feature of our plan for the synthesis of
the larger fragment 2 (C-1 to C-18) of pamamysin 621A
is shown in Scheme 1. The characteristic THF rings
were designed to be built from the linear precursor 3,
which already carried all stereogenic centers of
well-defined desired absolute configurations, via in-
tramolecular O-alkylations. In an earlier endeavor di-
rected to the synthesis of nonactin,5 we developed an
effective protocol for construction of similar THF rings
from the corresponding aldols without suffering other-
wise readily occurred side reactions associated with the
carbonyl groups β to the leaving groups. Judging from
the structural similarity of 2 and nonctin, such a plan
appeared to be feasible.
the only two members in the pamamycin family with
1
full H and 13C NMR data for the natural samples dis-
closed in the literature to date.1 Because of their in-
triguing structures and significant bioactivities,2 pama-
mycins have attracted considerable attention from the
synthetic community around the world soon after their
discovery. Many synthetic efforts,3 along with eight
total syntheses,4 are subsequently documented.
In a retrosynthetic sense, introduction of C-C double
and triple bonds between the C-4/C-5 and the
C-11/C-12 of 3 should make further disconnections
more feasible: The double bond would allow for dis-
connection of the C-1/C-2 sterogenic centers from the
C-5 to C-18 chain, giving smaller fragments 5 and 6.
The triple bond offered another excellent disconnecting
point, which divided the 6 into two even smaller frag-
ments, the Weinreb amide 7 and the alkyne 8.
The fragment 5a, which corresponds to the C-1 to
C-3 part of the target structure, is most readily attainable
from the aldol reaction between the N-acyl-oxazolidi-
none 9 and acrolein 10. As shown in Scheme 2, under
the conditions [TiCl4/TMEDA (N,N'-tetramethyl-
ethylenediamine)] originally reported by Crimmins,6 the
desired syn aldol was obtained in 73% isolated yield.
Further treatment with TESCl (triethylsilyl chloride)/
DMAP (4-dimethyl-aminopyridine) delivered the
Figure 1 Structures of pamamycins 621A (1a) and 607 (1b).
As the structures of the pamamycins are highly
similar to each other, clean separation of individual
components, especially those minor ones, is extremely
difficult. Further biological investigations therefore
have to rely mainly on synthetic samples, providing ad-
ditional stimulus to the synthetic investigations. Herein,
we wish to present some of our efforts directed toward
synthesis of the C-1 to C-18 fragment of pamamycins
607 and 621A.
*
E-mail: yikangwu@sioc.ac.cn
Received April 26, 2010; received May 21, 2010; accepted June 3, 2010.
Project supported by the National Basic Research Program of China (973 Program) (No. 2010CB833200), the National Natural Science Foundation
of China (Nos. 20921091, 20672129, 20621062, 20772143) and the Chinese Academy of Sciences (“Knowledge Innovation”, KJCX2.YW.H08).
† Dedicated to the 60th Anniversary of Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Chin. J. Chem. 2010, 28, 1651— 1659
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Ren & Wu
FULL PAPER
Scheme 1
TES protected aldol 5b.
resulting aldehyde was then subjected to a Crimmins
aldol reaction with oxazolidinethione 14 to deliver aldol
15. Finally, the oxazolidinthione chiral auxiliary was
replaced by a MeN(OMe) group through an exchange
reaction with MeNH(OMe)•HCl in the presence of imi-
dazole to give 16, showing that oxazolidinethione type
auxiliaries like thiazolidinethione type ones8 also enjoy
remarkable advantages at the auxiliary removal stage
compared with the more traditional oxazolidinones aux-
iliaries.
Scheme 2
Scheme 3
As the relative as well as the absolute stereochemis-
try at the C-6/C-7 is the same as at the C-2/C-3 part
embedded in 5, the C-5 to C-8 portion of the carbon
chain could be derived from 5 to simplify the synthesis.
Thus, removal of the oxazolidinone auxiliary from 5a
with LiBH4 in THF-Et2O in the presence of MeOH pro-
vided an intermediate diol, which on reaction with
PhCH(OMe)2 with catalysis of CSA [(±)-camphor-
10-sulfonic acid] afforded the known7 1,3-dioxane 11.
Reductive cleavage of the benzylidene group in 11 with
DIBAL-H (diisobutylaluminium hydride) yielded the
desired alcohol 12, also a previously known7 compound.
Elaboration of 12 into Weinreb amide 16, a conven-
ient precursor to the unstable fragment 7, is depicted in
Scheme 3. First, the primary alcohol was oxidized into
the corresponding aldehyde 13 by treatment with
(COCl)2/DMSO/Et3N in CH2Cl2 (Swern oxidation). The
The other fragment (C-11 to C-18) required for con-
struction of 6 was derived from the alcohol 17, a known
chiral building block readily accessible from (S)-malic
acid using the literature9 procedure. Swern oxidation of
17 followed by Grignard reaction with n-PrMgBr gave a
pair of alcohols 18a and 18b (separable on silica gel),
which on oxidation with Dess-Martin periodinane af-
forded the corresponding ketone 19 (Scheme 4, to make
full use of the undesired isomer).
The desired stereochemistry at the C-15 was then in-
stalled by a 1,3-induced asymmetric reduction10 with
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Studies on Synthesis of the C-1 to C-18 Fragment of Pamamycins 607 and 621A
Scheme 4
seemed to have occurred. However, quenching the reac-
tion with D2O did give deuteriated alkyne 8, proving
that the anion of 8 was indeed formed. Hence, the fail-
ure of further reaction of the acetylide with the amide
was most likely to be caused by the steric crowding
around the amide carbonyl group.
Scheme 5
LiAlH4/LiI. It is noteworthy that in this reaction 10 mo-
lar equivalent (with respect to ketone 19) of LiI proved
to be necessary for the desired stereoselectivity. Use of
less amounts of LiI or with LiCl instead all led to sig-
nificant loss of the setereoselectivity.
The newly introduced hydroxyl group was subse-
quently masked as a MOM (methoxymethyl) ether by
treatment with MOMCl/i-Pr2NEt in CH2Cl2. The ace-
tonide group in the resulting 20 was cleaved by treat-
ment with 50% aqueous F3CCO2H to yield an interme-
diate diol, which was transformed into the desired alco-
hol 22 via a three-step sequence: (1) acetyl protection of
the primary hydroxyl group with AcCl in the presence
of 2,6-lutidine at －78 ℃, (2) masking the secondary
hydroxyl group as a TBS (tert-butyldimethylsilyl) ether
using TBSCl/imidazole in DMF, and (3) reductive
cleavage of the Ac group with DIBAL-H to free the
primary hydroxyl group. The 22 was further oxidized
with Dess-Martin periodinane to yield the correspond-
ing aldehyde, which on further treatment with CBr4/
PPh3 followed by n-BuLi afforded4h alkyne 8.
The catenation of the C-5 to C-10 and C-11 to C-18
fragments was first attempted (Scheme 5) using direct
coupling of the Weinreb amide 7, which was prepared
from 16 via silylation with TMSCl (trimethylsilyl chlo-
ride) in the presence of imidazole, with lithiated 8 (gen-
erated in situ from alkyne 8 by reaction with either
n-BuLi or LiMe with or without HMPA (hexamethyl-
phosphoramide) at different temperatures even after
prolonged reaction time) without success. No reaction
Unable to realize direct coupling mentioned above,
we decided to switch to a more feasible alternative—to
achieve the same goal via the addition of the acetylide
to aldehyde 23 followed by oxidation of the resulting
propargyl alcohols. To this end, the amide 7 was re-
duced to the corresponding aldehyde 23 by reaction
with DIBAL-H at －78 ℃ in THF. Subsequent ex-
posure of 23 to the lithiated 8 led to expected propargyl
alcohol as a 1∶1 mixture of the two epimers, which
were oxidized into a single ketone 24 using Dess-Martin
oxidation with an overall yield (from 16) of 73%.
The TMS protecting group was then removed with
50% aqueous F3CCO2H to give the hydroxyketone 25 in
98% yield. With a free hydroxyl group at the carbon β
to the carbonyl group, the stage was set for Evans’
asymmetric reduction11 of the ketone. Thus, treatment
of 25 with Me4NBH(OAc)3 at －20 ℃ in MeCN-
AcOH afforded the 1,3-anti diol 26 in 92% yield. To
meet the functional group elaboration requirements at
later stages the hydroxyl groups were masked with
benzylidene group through an acetal exchange reaction
with PhCH(OMe)2 in the presence of a catalytic amount
of CSA in CH2Cl2.
Chin. J. Chem. 2010, 28, 1651— 1659
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FULL PAPER
According to our initial plan, construction of the full
linear chain that contains C-1 to C-18 (4) relied on a
cross metathesis (CM) reaction between fragments 5
and 6. Although there have been a huge number of
ring-closing metathesis reports in the literature, the
precedents of cross coupling between two fragments
carrying multi-functionalities/stereogenic centers are
scant. One of such examples was reported by Crimmins
and co-workers,12 which did not require large excess of
any of the two coupling partners as in most known CM
reactions, yet still gave reasonably good yield (68%).
One of the two substrates in their case bore a free hy-
droxyl group at the allylic position immediately next to
the reaction center, which appeared to be critical to the
success. Therefore, we decided to use 5a rather than
more hindered 5b in our CM attempts (Scheme 6).
However, to our disappointment with the Grubbs II
catalyst at different temperatures (r.t., refluxing CH2Cl2,
refluxing toluene, 130 ℃/sealed tube) in different sol-
vents (CH2Cl2 or toluene) with different reactant ratios
no acceptable results could be obtained. At low temp-
eratures essentially no reactions took place, while at
elevated temperatures extensive side products formation
occurred, with the desired 4a formed in ＜4% yield. As
this approach did not work out as planned, later we
turned to other alternatives, which eventually led to a
total synthesis of pamamycin 621A.4h
to C-18 chain via a cross metathesis reaction failed to
give expected coupling product in acceptable yields.
Experimental
Dry THF was distilled over Na/Ph2CO under N2
prior to use. Dry CH2Cl2 was distilled over CaH2 under
N2 prior to use. Addition of air/moisture sensitive re-
agents was done using syringe techniques. PE (for
chromatography) stands for petroleum ether (b.p. 60—
90 ℃). Column chromatography was performed on
silica gel (300—400 mesh) under slightly positive pres-
sure. CSA refers to (±)-camphor-10-sulfonic acid.
NMR spectra were recorded on a Varian Mercury 300
or a Bruker Avance 300 NMR spectrometer with Me4Si
as the internal standard. IR spectra were measured on a
FT-IR 440 or a Nicolet Avatar 360 infrared spectrome-
ter. ESI-MS data were acquired on a HP5989A mass
spectrometer. HRMS data were obtained with a Bruker
APEXIII 7.0 Tesla FT-MS spectrometer. Optical rota-
tions were measured on a Perkin-Elmer Polarimeter 341
or an Agilent Technologies P-1030 polarimeter. Ele-
mental analysis was performed with an Elementar
VarioEL III instrument.
(4R)-3-[(2R,3S)-3-Hydroxy-2-methyl-pent-4-eno-
yl]-4-phenyl-oxazolidin-2-one (5a) TiCl4 (4.8 mL,
44.0 mmol) was added (via a syringe) dropwise to a
solution of 9 (8.63 g, 140.0 mmol) in dry CH2Cl2 (240
mL) stirred at 0 ℃ (ice-water bath) under N2. After
completion of the addition, the mixture was stirred at
the same temperature for 10 min before dry TMEDA
(16.8 mL, 104.0 mmol) was introduced dropwise. The
dark red-brown mixture was stirred at 0 ℃ for another
30 min. A solution of aldehyde 10 (8.39 g, 149.8 mmol)
in dry CH2Cl2 (5 mL) was added dropwise. After com-
pletion of the addition, the mixture was stirred at the
same temperature for 1 h. Aqueous NH4Cl (20 mL) was
added. The mixture was filtered through Celite (washing
with CH2Cl2 three times). The filtrate and washings
were combined, washed with water and brine before
being dried over anhydrous Na2SO4. Removal of the
solvent on a rotary evaporator and column chromato-
graphy [V(EtOAc)∶V(PE)＝1∶45] on silica gel gave
enantiopure aldol 5a as a yellowish oil (8.02 g, 29.1
Scheme 6
Conclusion
1
mmol, 73%). [α]2D6 －86.9 (c 3.90, CHCl3); H NMR
(CDCl3, 300 MHz) δ: 7.41—7.26 (m, 5H), 5.86 (ddd,
J＝16.4, 10.9, 5.4 Hz, 1H), 5.46 (dd, J＝8.8, 3.8 Hz,
1H), 5.30 (d, J＝17.2 Hz, 1H), 5.19 (d, J＝10.4 Hz, 1H),
4.70 (t, J＝8.8 Hz, 1H), 4.49 (m, 1H), 4.26 (dd, J＝9.0,
3.8 Hz, 1H), 3.91 (dq, J＝3.3, 7.1 Hz, 1H), 2.82 (d, J＝
3.2 Hz, 1H), 1.15 (d, J＝7.1 Hz, 1H); 13C NMR (CDCl3,
75 MHz) δ: 176.1, 153.4, 138.8, 137.3, 129.3, 128.8,
125.5, 116.2, 72.3, 69.9, 57.5, 42.5, 10.8; FT-IR (film－) ν:
Attempts directed toward synthesis of the linear
precursor to the C-1 to C-18 fragment of pamamycins
607 and 621A are presented. The target chain structure
was planned to be built up from three subunits, which
contained the C-1 to C-4, C-5 to C-10, and C-11 to C-18,
respectively. Among the nine stereogenic centers spread
over the 18-carbon chain, the one at the C-13 was de-
rived from (S)-malic acid. The C-10 and C-15 stereo-
genic centers were installed via asymmetric reduction.
The remainders were generated using chiral auxiliary-
induced asymmetric aldol reactions. Catenation of the
C-5 to C-18 portion has been successfully achieved.
However, incorporation of the C-1 to C-4 onto the C-5
1
3525, 2982, 1773, 1699, 1476＋, 1418, 1201, 706 cm ;
ESI-MS m/z: 298.2 ([M＋Na] ); ESI-HRMS calcd for
C15H17NO4Na ([M＋Na]＋) 298.1050, found 298.1063.
(4R)-3-[(2R,3S)-3-Triethylsilyloxy-2-methyl-pent-
4-enoyl]-4-phenyl-oxazolidin-2-one (5b) A solution
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Chin. J. Chem. 2010, 28, 1651— 1659

Studies on Synthesis of the C-1 to C-18 Fragment of Pamamycins 607 and 621A
of 5a (681 mg, 2.48 mmol), imidazole (337 mg, 4.95
mmol), DMAP (15 mg, 0.12 mmol), and TESCl (0.64
mL, 3.72 mmol) in dry CH2Cl2 (8 mL) was stirred at
ambient temperature for 20 min. Water (10 mL) was
added. The mixture was extracted with Et2O (50 mL×
3). The combined organic layers were washed with wa-
ter and brine before being dried over anhydrous Na2SO4.
Removal of the solvent by rotary evaporation and col-
umn chromatography [V(EtOAc)∶V(PE)＝1∶10] on
silica gel gave 5b (947 mg, 2.43 mmol, 98%) as a white
solid. m.p. 64—66 ℃; [α]2D6 －95.4 (c 1.05, CHCl3);
1H NMR (CDCl3, 300 MHz) δ: 7.41—7.26 (m, 5H),
5.86 (ddd, J＝17.0, 10.4, 7.0 Hz, 1H), 5.37 (dd, J＝8.5,
3.3 Hz, 1H), 5.18 (d, J＝17.0 Hz, 1H), 5.11 (d, J＝10.4
Hz, 1H), 4.62 (t, J＝8.4 Hz, 1H), 4.30—4.23 (m, 2H),
4.06 (m, 1H), 1.12 (d, J＝6.5 Hz, 3H), 0.94 (t, J＝7.8
Hz, 9H), 0.57 (q, J＝7.6 Hz, 6H); FT-IR (film) ν: 2955,
2912, 2877, 1782, 1706, 1457, 138＋1, 1197, 848, 699
and brine before being dried over anhydrous Na2SO4.
Removal of the solvent by rotary evaporation and col-
umn chromatography [V(EtOAc)∶V(PE)＝1∶6] on
silica gel gave the known alcohol 12 (924 mg, 4.49
mmol, 74% from 5a) as a yellowish oil. [α]2D6 ＋39.4 (c
1
1.45, CHCl3); H NMR (CDCl3, 300 MHz) δ: 7.41—
7.26 (m, 5H), 5.86 (ddd, J＝17.7, 10.4, 7.8 Hz, 1H),
5.34 (dd, J＝10.6, 3.3 Hz), 5.18 (d, J＝17.6 Hz, 1H),
4.62 (d, J＝11.8 Hz, 1H), 4.61 (d, J＝11.8, 1H), 3.90
(dd, J＝7.2, 4.2 Hz, 1H), 3.70—3.51 (m, 2H), 2.51 (br s,
1H), 2.06—1.99 (m, 1H), 0.91 (d, J＝7.1 Hz, 1H).
(2S,3R,4R,5S)-5-Benzyloxy-1-[(4R)-4-benzyl-2-
thioxo-oxazolidin-3-yl]-3-hydroxy-2,4-dimethyl-hept-
6-en-1-one (16) DMSO (0.58 mL, 8.15 mmol) was
added dropwise to a solution of (COCl)2 (0.36 mL, 4.08
mmol) in dry CH2Cl2 (15 mL) stirred at －78 ℃. After
stirring for 30 min, a solution of alcohol 12 (600 mg,
2.91 mmol) in CH2Cl2 (3 mL) was introduced. Stirring
was continued at －78 ℃ for another 2 h. Et3N (2.1
mL, 14.6 mmol) was added dropwise. The cooling bath
was allowed to warm naturally to ambient temperature.
Aqueous NaHCO3 (10 mL) was added. The mixture was
extracted with Et2O (100 mL×3). The combined or-
ganic layers were washed with water and brine before
being dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chroma-
tography [V(EtOAc)∶V(PE)＝1∶5] on silica gel gave
aldehyde 13 (575 mg, 2.82 mmol, 97% from 12) as a
colorless oil.
－1
cm ; ESI-MS m/z: 412.1 ([M＋Na] ). Anal. calcd for
C21H31NO4Si: C 64.75, H 8.02, N 3.60; found C 64.90,
H 7.83, N 3.20.
(2S,3S)-2-Methyl-3-benzyloxy-pent-4-en-1-ol (12)
－1
LiBH4 (1.5 mol•L in THF, 6.0 mL, 9.0 mmol) was
added dropwise to a solution of 5a (1.658 g, 6.00 mmol)
in anhydrous Et2O (20 mL) and anhydrous MeOH (0.36
mL, 9.0 mmol) stirred at 0 ℃ under N2 (balloon). Af-
ter completion of the addition, the mixture was stirred at
the same temperature until TLC showed completion of
－1
the reaction. Aqueous NaOH (1.0 mol•L , 1.0 mL) was
added. The mixture was stirred for another hour before
the volatiles were removed on a rotary evaporator. The
residue was extracted with CH2Cl2 (50 mL×5). The
combined organic layers were dried over anhydrous
MgSO4. Solvents were removed by rotary evaporation.
The residue was dissolved in CH2Cl2 (20 mL). To this
solution CSA (130 mg, 0.6 mmol) was added, followed
by PhCH(OMe)2 (0.92 mL, 6.6 mmol). The mixture was
stirred at ambient temperature until TLC showed com-
pletion of the reaction. Aqueous saturated NaHCO3 was
added. The mixture was extracted with Et2O (50 mL×
4). The combined organic layers were washed with wa-
ter and brine before being dried over anhydrous Na2SO4.
Solvents were removed by rotary evaporation. To the
residue was triturated with Et2O to dissolve the inter-
mediate 11. The insoluble white solids (the recovered
chiral auxiliary) were filtered off. The filtrate was con-
centrated on a rotary evaporator to give a yellow oil,
which was dissolved in CH2Cl2 (10 mL) and stirred at 0
In another flask, a solution of 14 (220 mg, 0.88
mmol) in dry CH2Cl2 (9 mL) was stirred at －78 ℃
while TiCl4 (0.21 mL, 1.77 mmol) was introduced
dropwise. Stirring was continued at the same tempera-
ture for 15 min before i-Pr2NEt (0.17 mL, 0.97 mmol)
was introduced. The mixture was stirred at －78 ℃
for another 30 min. Then a solution of the above ob-
tained aldehyde 13 (98 mg, 0.48 mmol) in dry CH2Cl2
(1 mL) was introduced. Stirring was continued at －78
℃ until TLC showed completion of the reaction.
Aqueous NH4Cl was added. The mixture was extracted
with Et2O (20 mL×4). The combined organic layers
were washed with water and brine before being dried
over anhydrous Na2SO4. Removal of the solvent by ro-
tary evaporation and column chromatography
[V(EtOAc)∶V(PE)＝1∶8] on silica gel gave 15 (186
mg, 0.41 mmol, 85% from 13, 82% from 12) as a yel-
lowish oil, from which the following data were acquired.
ESI-MS m/z: 476.2 ([M＋Na]＋). ESI-HRMS calcd for
C26H31NO4SNa ([M＋Na]＋) 476.1866, found 476.1873.
A solution of the above obtained 15 (180 mg, 0.396
mmol), MeNH(OMe)•HCl (48 mg, 0.49 mmol), and
imidazole (41 mg, 0.62 mmol) in dry CH2Cl2 (4 mL)
was stirred at ambient temperature for several hours.
Another portion of MeNH(OMe)•HCl (48 mg, 0.49
mmol), and imidazole (121 mg, 1.86 mmol) was added.
After that, the mixture was stirred at ambient tempera-
ture for 4 d before being diluted with Et2O, washed with
water and brine, and dried over anhydrous Na2SO4.
－1
℃. To the solution DIBAL-H (1.0 mol•L in cyclo-
hexane, 10.0 mL, 10.0 mmol) was added dropwise. The
mixture was stirred at the same temperature until TLC
showed completion of the reaction. MeOH was added to
quench the excess hydride, followed by an aqueous so-
lution of sodium potassium tartrate. The mixture was
stirred at ambient temperature for 2 h, forming a
two-phase system. The phases were separated. The
aqueous layer was extracted with CH2Cl2 (50 mL×3).
The combined organic layers were washed with water
Chin. J. Chem. 2010, 28, 1651— 1659
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Removal of the solvent by rotary evaporation and col-
umn chromatography [V(EtOAc)∶V(PE)＝1∶7] on
silica gel gave 16 (116 mg, 0.361 mmol, 91% from 15,
75% from 12) as a colorless oil. [α]2D6 ＋9.2 (c 1.21,
CHCl3); 1H NMR (CDCl3, 300 MHz) δ: 7.33—7.24 (m,
5H), 5.86 (ddd, J＝17.3, 10.7, 6.6 Hz, 1H), 5.30 (d, J＝
17.2 Hz, 1H), 5.23 (d, J＝10.3 Hz, 1H), 4.60 (d, J＝
11.7 Hz, 1H), 4.40—4.36 (m, 2H), 4.15 (d, J＝2.7 Hz,
1H), 3.90—3.85 (m, 1H), 3.65 (s, 3H), 3.18 (s, 3H),
3.00 (br, 1H), 1.70—1.65 (m, 1H), 1.26 (d, J＝7.0 Hz,
3H), 0.91 (d, J＝7.1 Hz, 3H); 13C NMR (CDCl3, 75
MHz) δ: 138.8, 137.6, 128.3, 127.7, 127.4, 116.8, 79.3,
73.2, 61.5, 40.4, 36.4, 10.4, 9.9; FT-IR (film) ν: 3470,
(CDCl3, 75 MHz) δ: 208.7, 108.7, 71.7, 69.4, 46.8, 45.3,
26.8, 25.4, 17.0, 13.6; FT-IR (film) ν: 2986, 2936, 2876,
－1
1712, 1379, 1052, 848 cm ; ESI-MS m/z: 209.1 ([M＋
Na]＋); ESI-HRMS calcd for C10H18ONa ([M＋Na]＋)
209.1148, found 209.1147.
(2S)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-pen-
tan-2-ol (18a) via reduction of 19 LiI (540 mg, 4.03
mmol) was added to a solution of 19 (75 mg, 0.403
mmol) in dry Et2O (8 mL) stirred at －40 ℃. The
mixture was stirred for 10 min to result in a yellow so-
lution. The temperature of the cooling bath was lowered
to －78 ℃. LiAlH4 (78 mg, 2.02 mmol) was added in
one portion. The mixture was stirred at the same tem-
perature until TLC showed completion of the reaction.
MeOH (5 mL) was added (still at －78 ℃) to destroy
excess hydride, followed by an aqueous solution of so-
dium potassium tartrate. The mixture was stirred while
the bath temperature was allowed to warm to ambient
temperature. The mixture was extracted with EtOAc (20
mL×3). The phases were combined, washed with water
and brine, and dried over anhydrous Na2SO4. Removal
of the solvent by rotary evaporation and column chro-
matography [V(EtOAc)∶V(PE)＝1∶3] on silica gel
gave 18a (60 mg, 0.319 mmol, 79%) and 18b (5 mg,
0.027 mmol, 6.7%) as colorless oils.
－1
2972, 2938, 1637, 1458, 1420＋, 1389, 1067, 996 cm ;
ESI-MS m/z: 344.1 ([M＋Na] ); ESI-HRMS calcd for
C18H27NO4Na ([M＋Na]＋) 344.1836, found 344.1832.
1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-pentan-
one (19) DMSO (0.15 mL, 2.04 mmol) was added
dropwise to a solution of (COCl)2 (90 µL, 1.02 mmol)
in dry CH2Cl2 (6 mL) stirred at －78 ℃. After stirring
for 30 min, a solution of alcohol 17 (125 mg, 0.86 mmol)
in CH2Cl2 (3 mL) was introduced. Stirring was contin-
ued at －78 ℃ for another 2 h. Et3N (0.60 mL, 4.30
mmol) was added dropwise. The cooling bath was al-
lowed to warm naturally to ambient temperature.
Aqueous NaHCO3 was added. The mixture was ex-
tracted with Et2O (100 mL×4). The combined organic
layers were washed with water and brine before being
dried over anhydrous MgSO4. Solvents were removed
by rotary evaporation. The residue was dissolved in dry
Et2O (3 mL) and cooled to －78 ℃. A solution of
Data for 18a. [α]D24 ＋6.4 (c 2.35, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ: 4.32—4.24 (m, 1H), 4.10 (t, J＝
7.1 Hz, 1H), 3.86—3.78 (m, 1H), 3.56 (t, J＝7.4 Hz,
1H), 3.12 (br, 1H), 1.72—1.60 (m, 2H), 1.60—1.22 (m,
4H), 1.42 (s, 3H), 1.36 (s, 3H), 0.93 (t, J＝6.9 Hz, 3H);
13C NMR (CDCl3, 75 MHz) δ: 109.2, 75.8, 70.6, 69.7,
40.3, 39.6, 26.8, 25.7, 18.5, 14.0; FT-IR (film) ν: 3443,
－1
n-PrMgBr (1.0 mol•L in THF, 2.0 mL, 2.0 mmol) was
－1
added dropwise. The mixture was stirred at the same
temperature until TLC showed completion of the reac-
tion. Aqueous saturated NH4Cl was added. The mixture
was extracted with Et2O (20 mL×3). The combined
organic layers were washed with water and brine before
being dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatog-
raphy [V(EtOAc)∶V(PE)＝1∶4] on silica gel gave 18a
and 18b as colorless oils (135 mg, 0.717 mmol, 83%
from 17, with data for 18a/18b listed in next experi-
ment). The two alcohols were dissolved in dry CH2Cl2
(2 mL). To this solution was added Dess-Martin perio-
dinane (609 mg, 1.434 mmol), followed by NaHCO3
(301 mg, 3.585 mmol). The mixture was stirred at am-
bient temperature until TLC showed completion of the
reaction before being diluted with Et2O (50 mL) and
filtered through Celite. The filtrate and ethereal wash-
ings were combined and chromatographed [V(EtOAc)∶
V(PE)＝1∶5] on silica gel to give ketone 19 (132 mg,
0.701 mmol, 98% from 18a/18b, 82% from 17) as a
2985, 2873, 1060, 870, 826 cm ; EI-MS m/z (%): 173
([M－CH3]＋), 43 (100); EI-HRMS calcd for C9H17O3
([M－CH3]＋) 173.1178, found 173.1180.
1
Data for 18b. [α]D24 －2.03 (c 1.35, CHCl3); H
NMR (CDCl3, 300 MHz) δ: 4.40—4.30 (m, 1H), 4.09
(br t, J＝7.1 Hz, 1H), 3.85—3.77 (m, 1H), 3.58 (dt, J＝
1.7, 8.0 Hz, 1H), 2.35 (br, 1H), 1.80—1.58 (m, 2H),
1.52—1.30 (m, 4H), 1.44 (s, 3H), 1.36 (s, 3H), 0.93 (t,
J＝6.7 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ: 108.7,
73.6, 69.5, 68.6, 39.9, 39.8, 26.9, 25.6, 18.8, 14－.0;
1
FT-IR (film) ν: 3443, 2985, 2873,＋1060, 870, 826 cm ;
EI-MS m/z (%): 173 ([M－CH3] ), 43 (100), 95 (81);
EI-HRMS calcd for C10H20O3 188.1412, found
188.1414.
(2S)-1-((4S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-
met-hoxymethyl-pentane (20) i-Pr2NEt (0.78 mL,
4.52 mmol) was added to a solution of 18a (85 mg,
0.452 mmol) and DMAP (28 mg, 0.23 mmol) in dry
CH2Cl2 (5 mL) stirred at ambient temperature. The
mixture was stirred for 30 min before MOMCl (0.17 mL,
2.26 mmol) was introduced (with cooling in a 0 ℃
bath). The mixture was stirred at ambient temperature
until TLC showed completion of the reaction. Aqueous
NaHCO3 was added. The mixture was extracted with
Et2O (50 mL×3). The organic phases were combined,
washed with water and brine, and dried over anhydrous
1
colorless oil. [α]D24 ＋21.7 (c 1.65, CHCl3); H NMR
(CDCl3, 300 MHz) δ: 4.50—4.40 (m, 1H), 4.18 (t, J＝
6.7 Hz, 1H), 3.53 (t, J＝7.8 Hz, 1H), 2.89 and 2.56
(ABX, JAB＝6.7 Hz, JAX＝6.1 Hz, JBX＝7.2 Hz, 2H),
2.43 (t, J＝7.0 Hz, 2H), 1.67—1.55 (m, 2H), 1.40 (s,
3H), 1.35 (s, 3H), 0.92 (t, J＝7.5 Hz, 3H); 13C NMR
1656
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1651— 1659

Studies on Synthesis of the C-1 to C-18 Fragment of Pamamycins 607 and 621A
Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography [V(EtOAc)∶V(PE)＝1∶
10] on silica gel gave 20 (87 mg, 0.375 mmol, 83%) as
a colorless oil. [α]2D4 ＋17.7 (c 1.65, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ: 4.61 (s, 2H), 4.18 (quint, J＝6.4
Hz, 1H), 4.05 (dd, J＝6.0, 7.9 Hz, 1H), 3.62 (quint, J＝
5.9 Hz, 1H), 3.50 (t, J＝7.6 Hz, 1H), 3.36 (s, 3H),
1.95—1.88 (m, 1H), 1.71—1.60 (m, 1H), 1.54—1.47
(m, 2H), 1.40—1.32 (m, 2H), 1.39 (s, 3H), 1.33 (s, 3H),
0.90 (t, J＝7.0 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ:
108.5, 95.3, 74.7, 73.1, 69.7, 55.6, 38.0, 36.5, 26.9, 25－.7,
reaction. MeOH (1 mL) was added, followed by Et2O
(30 mL) and aqueous sodium potassium tartrate. The
mixture was stirred at ambient temperature until a two
phase clear system was formed. The product was taken
into Et2O by repeated extraction (30 mL×3). The or-
ganic phases were combined, washed with water and
brine, and dried over anhydrous MgSO4. Removal of the
solvent by rotary evaporation and column chromatog-
raphy [V(EtOAc)∶V(PE)＝1∶1] on silica gel afforded
alcohol 22 (43 mg, 0.141 mmol, 75% from 21) as a col-
1
orless oil. [α]2D4 ＋ 22.6 (c 2.20, CHCl3); H NMR
1
18.5, 14.1; FT-IR (film) ν: 2985, 2935, 2875, 1040 cm ;
(CDCl3, 300 MHz) δ: 4.63 (d, J＝7.1 Hz, 1H), 4.60 (d,
J＝7.1 Hz, 1H), 3.95—3.88 (m, 1H), 3.67—3.60 (m,
1H), 3.59—3.42 (m, 2H), 3.36 (s, 3H), 2.28 (br, 1H),
1.74—1.69 (m, 2H), 1.58—1.42 (m, 2H), 1.41—1.26
(m, 2H), 0.90 (t, J＝7.3 Hz, 3H), 0.88 (s, 9H), 0.07 (s,
6H); 13C NMR (CDCl3, 75 MHz) δ: 95.3, 74.4, 69.9,
65.9, 55.7, 38.8, 36.9, 25.7, 18.4, 18.0, 14.1, －4.7;
FT-IR (film) ν: 3481, 2956, 2930, 2858, 1464, 10＋39,
ESI-MS m/z: 255.1 ([M＋Na]＋); ESI-HRMS calcd for
C12H24O4Na ([M＋Na]＋) 255.1567, found 255.1575.
(2S,4S)-4-Methoxymethoxy-heptane-1,2-diol (21)
A solution of 20 (53 mg, 0.229 mmol) and aqueous
F3CCO2H (50%, 0.2 mL) in CH2Cl2 (8 mL) was stirred
at ambient temperature until TLC showed completion of
the reaction. Aqueous saturated NaHCO3 was added.
The mixture was extracted with EtOAc (30 mL×4).
The organic phases were combined, washed with water
and brine, and dried over anhydrous Na2SO4. Removal
of the solvent by rotary evaporation and column chro-
matography [V(EtOAc)∶V(PE)＝1∶1] on silica gel
gave diol 21 (39 mg, 0.203 mmol, 89%) as a colorless
oil. [α]2D4 ＋52.1 (c 1.80, CHCl3); 1H NMR (CDCl3, 300
MHz) δ: 4.69 (d, J＝6.7 Hz, 2H), 3.88—3.78 (m, 2H),
3.69 (br, 1H), 3.64—3.45 (m, 2H), 3.40 (s, 3H), 2.92 (br,
1H), 1.80—1.42 (m, 4H), 1.40—1.22 (m, 2H), 0.92 (t,
J＝6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ: 95.1,
76.8, 71.0, 66.7, 55.7, 37.4, 36.5, 18.1, 14.1; FT-IR
－ 1
836, 776 cm ; ESI-MS m/z: 329.2 ([M＋Na] ＋).
ESI-HRMS calcd for C15H34O4SiNa ([M ＋ Na]
)
329.2119, found 329.2130.
(3S,4R,5R,6S,10S,12S)-3-Benzyloxy-10-(tert-but-
yldimethylsilyloxy)-12-methoxymethoxy-4,6-dimeth-
yl-5-trimethylsilyloxy-pentadec-1-en-8-yn-7-one (24)
TMSCl (0.26 mL, 2.037 mmol) was added dropwise to
a solution of 16 (218 mg, 0.680 mmol) and imidazole
(183 mg, 2.716 mmol) in dry CH2Cl2 (7 mL) stirred in
an ice-water bath. The mixture was stirred at the same
temperature until TLC showed completion of the reac-
tion. Aqueous NaHCO3 was added. The mixture was
extracted with Et2O (100 mL×3). The organic phases
were combined, washed with water and brine, and dried
over anhydrous Na2SO4. Removal of the solvent by ro-
tary evaporation and column chromatography
[V(EtOAc)∶V(PE)＝1∶6] on silica gel afforded 7
(269 mg, 0.68 mmol, 100%) as a colorless oil. A portion
of this oil (119 mg, 0.302 mmol) was dissolved in dry
THF (3.0 mL) and cooled in a －78 ℃ bath. To this
－1
(film) ν: 3422, 2934,＋2874, 1466, 1035 cm ; ESI-MS
m/z: 215.0 ([M＋Na] ). ESI-HRMS calcd for C9H20O4-
Na ([M＋Na]＋) 215.1254, found 215.1255.
(2S,4S)-2-tert-Butyldimethylsilyloxy-4-methoxy-
methoxy-heptanol (22) Acetyl chloride (14.6 µL,
0.206 mmol) was added dropwise to a solution of 21 (36
mg, 0.187 mmo) and 2,6-lutidine (46.4 µL, 0.374 mmol)
in dry CH2Cl2 (2 mL) stirred at －78 ℃. The mixture
was stirred until TLC showed completion of the reaction.
MeOH (1 mL) was added, followed by aqueous sodium
potassium tartrate. Stirring was continued to give a
two-phase clear system. The mixture was extracted with
Et2O (30 mL×3). The organic phases were combined,
washed with water and brine, and dried over anhydrous
Na2SO4. Solvents were removed by rotary evaporation.
The residue was dissolved in dry DMF (1 mL), to which
imidazole (64 mg, 0.935 mmol), DMAP (23 mg, 0.187
mmol), and TBSCl (57 mg, 0.374 mmol) were added in
turn. The mixture was stirred at ambient temperature
until TLC showed completion of the reaction before
being diluted with Et2O, washed with water and brine,
and dried over anhydrous Na2SO4. The solvent was re-
moved by rotary evaporation. The residue was dissolved
in dry CH2Cl2 (2 mL) and cooled in a －78 ℃ bath.
－1
solution was added DIBAL-H (1.0 mol•L in cyclohe-
nane, 0.60 mL, 0.60 mmol). Stirring was continued at
－78 ℃ until TLC showed completion of the reaction.
MeOH (5 mL) was added, followed by Et2O (100 mL)
and aqueous sodium potassium tartrate. The mixture
was stirred at ambient temperature until a two-phase
clear system was formed. The product was taken into
Et2O by repeated extraction (20 mL×3). The organic
phases were combined, washed with water and brine,
and dried over anhydrous Na2SO4. Removal of the sol-
vent by rotary evaporation and column chromatography
[V(EtOAc)∶V(PE)＝1∶15] on silica gel afforded al-
dehyde 23 (101 mg, 0.302 mmol, 100% from 16 or 7) as
a colorless oil. A portion of this aldehyde (58 mg, 0.173
mmol) was dissolved in dry THF (3.0 mL) and cooled
in a －78 ℃ bath. This solution was added via a can-
nula to a solution of lithiated 8 (prepared by treating a
solution of 8 (134 mg, 0.－447 mmol) in dry THF (3.0 mL)
－1
To this solution were added DIBAL-H (1.0 mol•L in
cyclohenane, 0.37 mL, 0.37 mmol). Stirring was con-
1
tinued at －78 ℃ until TLC showed completion of the
with n-BuLi (1.6 mol•L in hexanes, 0.33 mL, 0.526
Chin. J. Chem. 2010, 28, 1651— 1659
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1657

Ren & Wu
FULL PAPER
mmol) at －78 ℃ for 30 min). The mixture was then
stirred at the same temperature for 2 h. Water was added
to quench the reaction. The mixture was extracted with
Et2O (50 mL×4). The organic phases were combined,
washed with water and brine, and dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography [V(EtOAc)∶V(PE)＝1∶
15] on silica gel afforded the propargyl alcohols (81 mg,
0.128 mmol, 74% from 16) as a colorless oil.
A portion of the propargyl alcohols (66 mg, 0.104
mmol) was dissolved in dry CH2Cl2 (1 mL). To this so-
lution were added Dess-Martin periodinane (132 mg,
0.311 mmol) and NaHCO3 (87 mg, 1.04 mmol). The
mixture was stirred at ambient temperature for 20 min.
About half of the solvent was removed by rotary
evaporation. The residue was chromatographed
[V(EtOAc)∶V(PE)＝1∶15] on silica gel to give ketone
24 (61 mg, 0.0964 mmol, 93% from the alcohols, 69%
butyldimethylsilyloxy)-12-methoxymethoxy-4,6-di-
methylpentadec-1-en-8-yn-5,7-diol (26) A solution
of ketone 25 (52 mg, 0.0932 mmol) in an dry MeCN
(1.0 mL) was added to a solution of Me4NBH(OAc)3
(262 mg, 1.00 mmol) in glacial HOAc (1.0 mL) and dry
MeCN (1.0 mL) stirred at －20 ℃. Stirring was then
continued at the same temperature fo－r 14 h. Aqueous
1
sodium potassium tartrate (1.0 mol•L , 1.0 mL) was
added, followed by Et2O. The pH of the aqueous layer
was adjusted to ca. 8 with aqueous saturated NaHCO3.
The mixture was extracted with Et2O (20 mL×5). The
organic phases were combined, washed with water and
brine, and dried over anhydrous Na2SO4. Removal of
the solvent by rotary evaporation and column chroma-
tography [V(EtOAc)∶V(PE)＝1∶8] on silica gel af-
forded diol 26 (48 mg, 0.086 mmol, 92%) as a colorless
oil. [α]2D5 －30.7 (c 2.25, CHCl3); 1H NMR (CDCl3, 300
MHz) δ: 7.36—7.25 (m, 5H), 5.95 (ddd, J＝17.7, 10.2,
7.9 Hz, 1H), 5.37 (d, J＝10.6 Hz, 1H), 5.28 (d, J＝17.4
Hz, 1H), 4.67—4.56 (m, 4H), 4.41—4.26 (m, 3H), 4.04
(s, 1H), 3.96 (m, 1H), 3.80—3.74 (m, 2H), 3.36 (s, 3H),
2.04—1.89 (m, 2H), 1.80—1.21 (m, 6H), 1.02 (d, J＝
7.5 Hz, 3H), 0.90 (t, J＝7.4 Hz, 3H), 0.88 (s, 9H), 0.09
(d, J＝7.1 Hz, 6H); FT-IR (film) ν: 3459, 2929, 2857,
from 16) as a colorless oil. [α]D25

1H NMR (CDCl3, 300 MHz) δ: 7.37—7.25 (m, 5H),
5.89 (ddd, J＝17.1, 10.7, 6.6 Hz, 1H), 5.30 (d, J＝16.8
Hz, 1H), 5.28 (d, J＝11.0 Hz, 1H), 4.70 (t, J＝6.7 Hz,
1H), 4.62 (s, 2H), 4.61 (d, J＝11.8 Hz, 1H), 4.34 (d, J＝
11.8 Hz, 1H), 4.50 (d, J＝8.7 Hz, 1H), 4.13 (d, J＝7.4
Hz, 1H), 3.75—3.67 (m, 1H), 3.35 (s, 3H ), 2.80—2.70
(m, 1H), 2.01—1.80 (m, 1H ), 1.72—1.60 (m, 2H),
1.54—1.27 (m, 4H), 1.14 (d, J＝6.9 Hz, 3H), 0.97—
0.91 (m, 15H),＋0.13—0.19 (m, 15H); ESI-MS m/z:
655.7 ([M＋Na] ); ESI-HRMS calcd for C35H60O6NaSi
([M＋Na]＋) 655.3821, found 655.3845.
－1
1463, 1040, 838, 778 cm ; ESI-MS m/z: 585.5 ([M＋
Na]＋); MALDI/DHB calcd for C32H54SiO6Na ([M＋
Na]＋) 585.3582, found 583.3553.
(3S,5S)-1-[(4S,5S,6R)-6-((2R,3S)-2-Methyl-3-ben-
zyloxy-buta-3-enyl)-2-phenyl-5-methyl-1,3-dioxan-4-
yl]-3-tert-butyldimethylsilyl-5-methoxymethoxy-1-oc-
tyne (6) A solution of 26 (11 mg, 0.0196 mmol), CSA
(2 mg), and PhCH(OMe)2 (6 µL, 0.0392 mmol) in dry
CH2Cl2 (0.5 mL) was stirred at ambient temperature for
1 d. Another portion of PhCH(OMe)2 (12 µL, 0.0784
mmol) was added. Stirring was continued at ambient
temperature until TLC showed completion of the reac-
tion. The mixture was diluted with EtOAc (50 mL),
washed in turn with aqueous saturated NaHCO3, water,
and brine before being dried over anhydrous Na2SO4.
Removal of the solvent by rotary evaporation and col-
umn chromatography [V(EtOAc)∶V(PE)＝1∶15] on
silica gel gave 6 (12 mg, 0.0185 mmol, 94%) as a col-
(3S,4R,5R,6S,10S,12S)-3-Benzyloxy-10-(tert-butyl-
dimethylsilyloxy)-12-methoxymethoxy-4,6-dimethyl-
5-hydroxy-pentadec-1-en-8-yn-7-one (25) Aqueous
F3CCO2H (50%, 0.7 mL) was added dropwise to a solu-
tion of 24 (60 mg, 0.095 mmol) in CH2Cl2 (3.2 mL)
stirred at ambient temperature. Stirring was continued at
the same temperature for 5 min. Aqueous saturated
NaHCO3 was added. The mixture was extracted with
Et2O (10 mL×3). The organic phases were combined,
washed with water and brine, and dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography [V(EtOAc)∶V(PE)＝1∶8]
on silica gel afforded hydroxyketone 25 (52 mg, 0.0932
1
orless oil. H NMR (CDCl3, 300 MHz) δ: 7.38—7.25
mmol, 98%) as a colorless oil. [α]D25
(m, 10H), 5.80 (ddd, J＝17.7, 10.2, 7.9 Hz, 1H), 5.32—
5.24 (m, 3H), 4.72—4.60 (m, 5H), 4.34—4.28 (m, 2H),
3.87 (d, J＝10.0 Hz, 1H), 3.81—3.75 (m, 1H), 3.35 (s,
3H), 2.04—1.89 (m, 2H), 1.80—1.21 (m, 6H), 1.19 (d,
J＝6.9 Hz, 3H), 0.94—0.82 (m, 15H), 0.12 (d, J＝10.5
Hz, 6H); ESI-MS m/z: 673.6 ([M＋Na]＋＋); MALDI/
DHB calcd for C39H58SiO6Na ([M＋Na] ) 673.3895,
found 673.3897.
CHCl3); 1H NMR (CDCl3, 300 MHz) δ: 7.37—7.27 (m,
5H), 5.91 (ddd, J＝17.5, 10.4, 7.3 Hz, 1H), 5.37 (d, J＝
9.6 Hz, 1H), 5.29 (d, J＝17.5 Hz, 1H), 4.71 (t, J＝6.6
Hz, 1H), 4.65 (s, 2H), 4.65 (d, J＝11.5 Hz, 1H), 4.34 (d,
J＝11.5 Hz, 1H), 4.24—4.15 (m, 2H), 3.80—3.70 (m,
1H), 3.44 (d, J＝4.1 Hz, 1H), 3.38 (s, 3H), 2.65—2.55
(m, 1H), 1.97—1.82 (m, 1H), 1.56—1.49 (m, 2H), 1.43
—1.26 (m, 4H), 1.20 (d, J＝7.3 Hz, 3H), 0.97—0.91 (m,
15H), 0.14 (d, J＝9.4 Hz, 6H); FT-IR (film) ν: 3496,
References
3031, 2960, 2208, 1678, 1496＋, 1463, 836, 779 cm ;
1
For an excellent review, see: Metz, P. Top. Curr. Chem.
2005, 244, 215.
ESI-MS m/z: 583.4 ([M＋Na] )＋; MALDI/DHB calcd
for C32H52SiO6Na ([M ＋ Na] ) 583.3425, found
583.3454.
2
(a) Kozone, I.; Hashimoto, M.; Gräfe, U.; Kawaide, H.; Abe,
H.; Natsume, M. J. Antibiot. 2008, 61, 98.
(3S,4R,5R,6S,7S,10S,12S)-3-Benzyloxy-10-(tert-
1658
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1651— 1659

Studies on Synthesis of the C-1 to C-18 Fragment of Pamamycins 607 and 621A
(b) Lefevre, P.; Peirs, P.; Braibant, M.; Fauville-Dufaux, M.;
Vanhoof, R.; Huygen, K.; Wang, X.-M.; Pogell, B.; Wang,
Y.; Fischer, P.; Metz, P.; Content, J. J. Antimicrob. Chemo-
ther. 2004, 54, 824.
(d) Wang, Y.; Bernsmann, H.; Gruner, M.; Metz, P.
Tetrahedron Lett. 2001, 42, 7801.
(e) Kang, S. H.; Jeong, J. W.; Hwang, Y. S.; Lee, S. B.
Angew. Chem., Int. Ed. 2002, 41, 1392.
(c) For reviews, see: Pogell, B. M. Cell. Mol. Biol. (Paris)
1998, 44, 461.
(a) Walkup, R. D.; Kim, Y. S. Tetrahedron Lett. 1995, 36,
3091.
(f) Lanners, S.; Norouzi-Arasi, H.; Salom-Roig, X. J.; Han-
quet, G. Angew. Chem., Int. Ed. 2007, 46, 7086.
(g) Fischer, P.; Segovia, A. B. G.; Gruner, M.; Metz, P.
Angew. Chem., Int. Ed. 2005, 44, 6231.
3
(b) Fraser, B.; Mulder, R. J.; Perlmutter, P. Tetrahedron
2006, 62, 2857.
(c) Mandville, G.; Bloch, R. Eur. J. Org. Chem. 1999, 2303.
(d) Lanners, S.; Norouzi-Arasi, H.; Khiri, N.; Hanquet, G.
Eur. J. Org. Chem. 2007, 4065.
(e) Calter, M. A.; Bi, F. C. Org. Lett. 2000, 2, 1529.
(f) Bernsmann, H.; Gruner, M.; Frolich, R.; Metz, P.
Tetrahedron Lett. 2001, 42, 5377.
(g) Miura, A.; Takigawa, S.-Y.; Furuya, Y.; Yokoo, Y.;
Kuwahara, S.; Kiyota, H. Eur. J. Org. Chem. 2008, 4955.
(a) Germay, O.; Kumar, N.; Thomas, E. J. Tetrahedron Lett.
2001, 42, 4969.
(h) Ren, G.-B.; Wu, Y.-K. Org. Lett. 2009, 11, 5638.
Wu, Y.-K.; Sun, Y.-P. Org. Lett. 2006, 8, 2831.
Crimmins, M. T.; King, B. W.; Tabet, E. A. J. Am. Chem.
Soc. 1997, 119, 7883.
Anderson, J. C.; McDermott, B. P.; Griffin, E. J. Tetrahe-
dron 2000, 56, 54747.
Crimmins, M. T.; Chaudhary, K. Org. Lett. 2000, 2, 775.
Gaunt, M. J.; Jessiman, A. S.; Osini, P.; Tanner, H. R.;
Hook, D. F.; Ley, S. V. Org. Lett. 2003, 5, 4819.
5
6
7
8
9
10 Mori, Y.; Takeuchi, A.; Kageyama, H.; Suzuki, M. Tetra-
hedron Lett. 1988, 29, 5423.
11 Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem.
Soc. 1988, 110, 3560.
12 Crimmins, M. T.; Zhang, Y.; Diaz, F. A. Org. Lett. 2006, 8,
2369.
4
(b) Lee, E.; Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S.
K. J. Am. Chem. Soc. 2001, 123, 10131.
(c) Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S. K.; Lee,
E. J. Am. Chem. Soc. 2002, 124, 14655.
(E1004261 Li, L.)
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