Assembly of the southern macrocyclic half of (+)-spirastrellolide a through cyclic acetal tethered ring-closing metathesis and 1,3-anti-mukaiyama-aldol

Article abstract of DOI:10.3987/COM-12-S(N)54

We describe herein details of our efforts in syntheses of A-ring and BC-ring of (+)-spirastrellolide A. While the former would constitute a facile 12-step synthetic endeavor starting from 1,5-pentanediol, the latter would showcase a cyclic acetal-tethered

Full text of DOI:10.3987/COM-12-S(N)54

HETEROCYCLES, Vol. 86, No. 1, 2012
565
HETEROCYCLES, Vol. 86, No. 1, 2012, pp. 565 - 598. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 24th June, 2012, Accepted, 25th July, 2012, Published online, 6th August, 2012
DOI: 10.3987/COM-12-S(N)54
ASSEMBLY OF THE SOUTHERN MACROCYCLIC HALF OF
(+)-SPIRASTRELLOLIDE A THROUGH CYCLIC ACETAL TETHERED
RING-CLOSING METATHESIS AND 1,3-ANTI-MUKAIYAMA-ALDOL†
Yu Tang,*a Jin-Haek Yang,b Jia Liu,b Chao-Chao Wang,a Ming-Can Lv,a
Yi-Biao Wu,a Xue-Liang Yu,a Changhong Ko,b and Richard P. Hsung*b
aSchool of Pharmaceutical Science and Technology, Tianjin University, Tianjin,
300072, P. R. China
bDivision of Pharmaceutical Sciences, School of Pharmacy, and Department of
Chemistry, University of Wisconsin, Madison, WI 53705
tangyu@qibebt.ac.cn, rhsung@wisc.edu
Abstract – We describe herein details of our efforts in syntheses of A-ring and
BC-ring of (+)-spirastrellolide A. While the former would constitute a facile
12-step synthetic endeavor starting from 1,5-pentanediol, the latter would
showcase a cyclic acetal-tethered ring-closing metathesis [RCM] method that was
developed in our lab for de novo synthesis of spiroketals. Constructing the entire
Southern Half of the macrocycle would require 1,3-anti-Mukaiyama aldol
addition for connecting A-ring and BC-ring specifically at C10 and C11, thereby
culminating a 17-step approach for the Southern Macrocyclic Half linearly from
(+)-2,3-(O)-iso-propylidene-L-threitol. Also discussed here is the possibility of
pursuing a more convergent approach toward the assembly of the Southern Half
through first connecting A-ring and C-ring via acetal formation that would first
link together the free C13-OH with C17 at the spiro-BC-ring junction. An ensuing
application of our cyclic acetal-tethered RCM strategy to close B-ring would
adopt this cyclic acetal intermediate.
†This paper is dedicated to Professor Ei-Ichi NEgishi with the deepest respect in
honoring the special occasion of his 77th birthday.
INTRODUCTION
Roberge and Andersen et al. in 2003 unveiled the rough structure of (+)-spirastrellolide A, a macrocyclic

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HETEROCYCLES, Vol. 86, No. 1, 2012
lactone that is rich in spiroketal motifs.1a Subsequently in 2004, they revised and completed the structural
assignment of (+)-spirastrellolide A including all relative stereochemistry sans C46.1b In 2007, with the
isolation of (+)-spirastrellolide B, the absolute configuration of the macrocyclic core was established
through X-ray crystallography.1c In the same year, (+)-spirastrellolide C-G were also identified from the
same marine sponge Spirastrella coccinea.1d (+)-Spirastrellolide A possess the ability to initiate
premature entry into mitosis and untimely mitotic arrest in cells, and more importantly, it exhibits a
potent inhibitory activity against protein phosphatase 2A [IC50 = 1 nM]. The level of inhibitory selectivity
is also outstanding in favor of PP2A over PP1 by a factor of 50 in terms of IC50.2 In addition,
(+)-spirastrellolide A does not inhibit PP2C! Its biological activities, therefore, resemble other known
Ser/Thr phosphatase inhibitors fostriecin and okadaic acid.3
CO2H
OH
CO2H
OH
CO2H
OH
46
46
46
OMe
OMe
OMe
O
O
O
O
O
O
28
28
28
O
O
O
Cl
H
H
4
4
4
1
O
O
O
O
O
O
O
O
O
HO
H
HO
H
HO
H
HO
HO
HO
8
8
8
HO
OH
OMe
OH
OMe
OH
OMe
O O
O O
O O
HO
HO
HO
15
15
15
(+)-spirastrellolide A
(+)-spirastrellolide B
(+)-spirastrellolide C
CO2H
CO2H
CO2H
46
46
46
OH
OR
OH
OMe
Cl
OMe
OMe
Cl
O
O
O
O
O
O
28
28
28
O
O
O
Cl
4
X
4
4
O
O
O
O
O
O
O
O
O
HO
H
HO
H
HO
H
HO
HO
HO
8
8
8
OH
OMe
OH
OMe
OH
OMe
O O
O O
O O
HO
HO
HO
15
15
15
(+)-spirastrellolide D
E: R = H; X = H; G: R = Me; X = Cl
(+)-spirastrellolide F
Figure 1. Spirastrellolides A-G.
Development of protein phosphatase inhibitors has lagged behind the interest in kinase inhibitors because
of the perceived notion that kinases are more highly regulated and specific.4 However, there has been a
renewed interest in recent years because reversible protein phosphorylation is critical "as the other half"
of checkpoints in cell cycles, and protein phosphatases assume an equally important role in regulating
cellular signal transductions and should not be ignored. Designing phosphatase inhibitors can lead to new
paradigms in developing cancer therapeutics.4 As a result, this family of natural products has attracted an

HETEROCYCLES, Vol. 86, No. 1, 2012
567
elegant array of synthetic efforts5 with the very first total synthesis being reported by Paterson.6 We
became interested in spirastrellolide A because we have been developing cyclic acetal tethered methods7a-c
such as RCM7d-g,8 as an unconventional approach to constructing spiroketals.9 We report here our efforts
toward the Southern Half of macrocyclic core of (+)-spirastrellolide A.
RESULTS AND DISCUSSION
1.
Retrosynthetic Analysis.
Our synthetic analysis would first involve a disconnection at C40-41 that will be reconnected through
Julia-Kocienski olefination, which was also documented in Smith5j [Scheme 1]. Consequently, this would
leave behind the central macrocyclic core [labeled as G-ring] that can be further divided into three major
fragments: 1 [C1 through C10], 2 [C11 through C23], and 3 [C24 through C40]. A macrolactonization
could link C1 and C37 between fragments 1 and 3. A methyl ketone enolate anti-aldol will be used to
connect fragments 1 and 2 at C10 and C11,5e,10 and another anti-aldolwould link together fragments 2 and
3 at C23 and C24 but will require the addition of the C25-oxo group. Synthesis of fragment 2 could
feature our cyclic acetal tethered RCM.7d-g
CO2H
C40-41:
Julia-Kocienski
46
40
E
O
3
P1O
OMe
O
OH
D
37
O
Cl
macrolactonization
40
E
OMe
Cl
O
O
F
41
O
D
H
O
25
OH
O
24
37
1
A
1
O
O
O
O
anti-aldol
A
10
O
G
24
O
O
O
HO
23
11
HO
H
23
11
H
22 OH
aldol
O
O
10
OH
O
O
B
C
1: C1-C10
OMe
B
C
HO
OMe
cyclic acetal
tethered RCM
(+)-spirastrellolide A
2: C11-C23
Scheme 1. An Overview of Retrosynthetic Plan for Spirastrellolides A.
2.
A-Ring Synthesis.
Our synthesis of A-ring10 would call for the commercially readily available 1,5-pentanediol as the starting
point. As shown in Scheme 2, 1,5-pentanediol could be quickly transformed into aldehyde 4 in 47%
overall yield via mono-benzylation and standard Swern oxidation. Standard HEW-modified
Wittig-olefination followed by DIBAL-H reduction afforded exclusively E-allylic alcohol 5 in 95%
overall yield. Sharpless asymmetric epoxidation employing D-(-)-diisopropyl tartrate provided epoxy
alcohol 6 in 96% enantiomeric excess. It is noteworthy that we have provided here a completely different
approach for establishing the C3 stereochemistry in A-ring of (+)-spirastrellolide A, as both Paterson5a-d,6
and De Brabander5g employed an asymmetric Brown-allylation.11a

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HETEROCYCLES, Vol. 86, No. 1, 2012
O
1)
1) NaH, THF; then BnBr, rt
OEt
OBn
, CH2Cl2, rt
2) (COCl)2, DMSO, Et3N, CH2Cl2
PPh3
HO
O
OBn
HO
2) DIBAL-H, CH2Cl2, – 78 oC
95% yield for 2 steps
OH
1,5-pentanediol
H
47% yield for 2 steps
4
5: E : Z ! 40 : 1
1) Red-Al, THF, -10 oC to rt
0.2 equiv Ti(O-iPr)4
OBn
MeO OMe
OBn
0.3 equiv (-)-diisopropyl tartrate
2)
, p-TsOH, acetone, rt
O
O
1
3
t-BuOOH, MS 4Å, CH2Cl2, – 20 oC
87% yield, 96 % ee
91% yield for 2 steps
O
HO
1
3
O
6
7
1)
1) 1 atm H2, 10% Pd/C, EtOH, rt
2) SO3-Py, DMSO, Et3N, CH2Cl2, 0 oC
Me
O
, THF, reflux
PPh3
OH OH
O
O
O
H
59% yield for 2 steps
2) p-TsOH-H2O
CH2Cl2, 0 oC
Me
8
9
key nOe
H
H
H
H
PivCl, Pyr, DMAP, CH2Cl2, rt
87% yield
1
9
Me
9
1
PivO
O
HO
O
Me
3
7
A
O
O
10: 87% yield for 2 steps
A-ring 11
Scheme 2. A Facile Assembly of the Pyranyl A-Ring 11.
A directed-reductive ring-opening of the epoxide proceeded regioselectively and a subsequent diol
protection using 2,2-dimethoxy propane gave acetonide 7. With the optically enriched acetonide 7 in
hand, we proceeded to complete the pyran synthesis. Debenzylation followed by Doering–Parikh
oxidation11b gave aldehyde 8. Wittig olefination and hydrolytic removal of the acetonide group occurred
concomitantly with the pyran formation yielded pyran 10 in 87% overall yield as a single diastereomer.
The relative syn stereochemical relationship at C3 and C7 was confirmed through NOE. Although kinetic
control has been noted,12 the high level of stereoselectivity is likely a result of thermodynamically
controlled O-1,4-addition, leading to complete chirality transfer from C3 to C7. Subsequent
Piv-protection of C1-OH in 10 gave methyl ketone 11, which would then complete our asymmetric
synthesis of A-ring, and set up the critical C10 and C11 connection via an anti-aldol [Scheme 1].
3.
BC-Ring Construction.
Synthesis of the Key Cyclic Acetal. Unlike the A-ring synthesis that featured asymmetric catalysis, to
prepare BC-ring, we elected the Hanessian’s chiron-pool concept and commenced with commercially
available (+)-2,3-(O)-iso-propylidene-L-threitol,10b,13a thereby borrowing the desired C21 and C22
stereochemistry. Mono-protection of the hydroxyl group in (+)-2,3-(O)-iso-propylidene-L-threitol with
TBDPSCl followed by Doering–Parikh oxidation11b gave aldehyde 12 in 68% yield [Scheme 3]. A

HETEROCYCLES, Vol. 86, No. 1, 2012
569
five-carbon chain extension of aldehyde 12 was accomplished with a five-step sequence: (i) Brown’s
asymmetric allylation to set up the C20 stereochemistry in a reagent controlled manner;11a (ii) standard
O-methylation to give methyl ether 13; (iii) classical 9-BBN hydroboration of 13; (iv) Doering–Parikh
oxidation,11b or modified-Moffat protocol, to afford aldehyde 14; and (v) vinyl Grignard addition to yield
allylic alcohol 15. Stereochemistry at C20 was confirmed using the classical Mosher ester analysis11c,d
after the Brown’s asymmetric allylation step using 12.
MgBr
1)
1) NaH, TBDPSCl, rt
O
O
O
O
O
O
21
20
H
OTBDPS
OTBDPS
OH
22
(-)-(Ipc)2BOMe
Et2O, – 78 oC
2) NaH, MeI, THF
2) SO3-Py, DMSO, Et3N
CH2Cl2, – 10 oC
O
OMe
HO
12: 68% yield overall
13: 43% yield overall
a single isomer
O
vinyl-MgBr, Et2O, – 78 oC
1) 9-BBN, THF, rt
OH
O
O
H
O
O
OTBDPS
OTBDPS
and then NaOH, H2O2
2) SO3-Pyr, DMSO, Et3N
OMe
OMe
14: 71% yield overall
15: 68% yield
Scheme 3. Synthesis of Aldehyde 14 and Allyl Alcohol 15.
1) AcOH/H2O (7:3), 70 oC
2) MnO2, CH2Cl2, rt
Tf2NH, – 78 oC
CH2Cl2
O
HO
OH
OH
O
O
O
OP
22
21
22
46% for 2 steps
OTBDPS
OMe
OMe
OP
OMe OH
OH
15: P = TBDPS
16: P = TBDPS
17
OH
O
O
H
O
O
O
22
21
OTBDPS
22
OP
OTBDPS
H
MeO
H
OMe OH
17: P = TBDPS
OMe OH
18: 81% yield
19: not detected
Scheme 4. Failed Attempt on Cyclic Acetal Construction from Allyl Alcohol 15.
At this juncture, we recognizing the potential of a more facile route to the key vinyl cyclic acetal, and thus,
we proceeded to remove the acetonide group in allylic alcohol 15, and a subsequent MnO2 oxidation gave
enone 16 that contains the free diol at C21 and C22 [Scheme 4]. However, attempts to access cyclic
acetal 19 from 16 through oxocarbenium ion 17 via acid promoted condensation with 1,6-heptadiene-4-ol
failed. From these attempts,14 we were only able to observe and/or isolate bicyclic acetal 18 in 81% yield
when using Tf2NH.15-17 The formation of 18 is clearly a result of trapping of vinyl oxocarbenium ion 17

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HETEROCYCLES, Vol. 86, No. 1, 2012
by the free C22-OH in a facile intramolecular manner. Given that 19 and 18 are both derived through 17
in a reversible manner, we tried but again failed at longer reaction time and higher temperatures to force
18 equilibrating toward 19.
After much experimentation, we ultimately suc ceeded in synthesizing the key vinyl cyclic acetal 25 via
the route shown in Scheme 5. Lindgren oxidation18 of aldehyde 14 afforded acid 20. Removal of the
acetonide group led to a selective lactone formation involving only C21-OH, and subsequent capping of
C22-OH with PivCl gave lactone 21 in 64% overall yield. The ensuing addition of vinyl magnesium
bromide followed by treatment of the resulting lactol mixture 22a/b with Tf2NH17 in the presence of
alcohol 2419a,b afforded the desired vinyl cyclic acetal 25 in 56% yield, albeit still accompanied with the
elimination product 26 that was not easily separable.
O
NaClO2, NaH2PO4
2-Me-2-butene
1) p-TsOH-H2O, CH2Cl2
O
O
O
H
O
O
OTBDPS
21 22
OTBDPS
HO
17
2) PivCl, Et3N, DMAP, CH2Cl2
OMe
OMe
14
20: 98% yield overall
O
OH
O
OH OP
vinyl-MgBr, THF, – 78 oC
OTBDPS
0.5 equiv Tf2NH
17
O
17
O
22
21
OP
CH2Cl2, 4 Å MS
– 78 oC, 1-3 min
OMe OPiv
22a
OMe OPiv
OMe OPiv
P = TBDPS
83% yield
22b
21: 64% yield overall
PMBO
OTBDPS
11
17
17
from 23
via
E1-elimination
H
OPiv
OMe
O
O
13
O O
17
OH
OTBDPS
OTBDPS
13
OMe OPiv
OMe OPiv
11
OPMB
23
26
24
25: 56% yield
Scheme 5. A Successful Route to Cyclic Acetal 25 from Aldehyde 14.
Exploring Conditions for the Cyclic Acetal Formation. Although we have developed our own unique
protocols for the acetal formation using simple pyranyl systems7,8 and that there are ample reports for
more robust carbohydrate systems,20 it is worthy to note that this particular cyclic acetal formation took
some efforts to investigate. As summarized in Table 1, formation of cyclic acetal using lactol 27 [epi at
C22], which contains the anomeric vinyl group at C17, proved to be challenging. A range of acids as well
as solvents and temperatures were screened. While most frequently used Lewis acids and Brønsted acids
in anomeric substitutions20 led to the over addition product 30, Tf2NH [entry 5] proved to be an excellent
Brønsted acid at –78 oC, leading to 29 as the sole product in 89% yield as a single diastereomer with the
oxo-butenyl group being axial.13b The ability of Tf2NH in leading to the desired outcome in an array of

HETEROCYCLES, Vol. 86, No. 1, 2012
571
reaction pathways have been well noted,15,16 albeit poorly understood other than the fact that represents
one softest anionic complex.17
Table 1. A Comparison of Acid Promoters in the Cyclic Acetal Formation.
O
OH
O
O
O
O
O
H
H
OH
O
OP
O
OP
17
OP
OP
OP
+
+
22
P = TBDPS
epi
MeO
OBn
MeO
OBn
MeO
OBn
MeO
OBn
MeO
OBn
27: P = TBDPS
29: 1,2-addition
30: 1,2-, and 1,4-add
31: elimination
28
entry
acid
equiv
solvent
temp
time
product
1.0
1.0
100 min
15 min
5-15 h
1-15 h
5 min
CH2Cl2
CH2Cl2
benzene
CH2Cl2
CH2Cl2
1
2
3
4
5
BF3-Et2O
TMSOTf
K-10
-78 oC
0
30 [82%]
30 [88%]
30 [89%]
No rxn
1.2-2.5
0.5-1.0
1.0
rt-reflux
rt-reflux
-78
CSA or PPTS
Tf2NH
29 [89%]
Cyclic Acetal-Tethered RCM. At last, the key ring-closing metathesis [RCM] of vinyl cyclic acetal 25 led
to BC-ring 32 in 95% yield using Grubbs' Generation-II Ru-catalyst [Scheme 6].21 It is noteworthy that
NOE experiments of 32 revealed its the desired relative stereochemistry, which closely resemble those
reported for the same region in spirastrellolide A.1 More importantly, the current synthesis of the
C11-C23 fragment 32 took only 12 steps from (+)-2,3-(O)-iso-propylidene-L-threitol.13a This chiron
approach is much shorter and synthetically more practical comparing to the previous 18-step route from
D-glucose, which also led to epi-stereochemistry at C22.13b We should point out that our synthetic study
represented the first in the area of spirastrellolide synthesis when we pursued the 18-step
C22-epi-synthesis, and the correct assignment had not been reported by Roberge and Andersen et al.
Our intent at the time was to simply showcase our strategy.
12 steps from (+)-2,3-(O)-iso-
key
propylidene-
L
-threitol
H
CH3
H
nOe
PMBO
OTBDPS
OPiv
20
H
H
OTBDPS
O
11
30 mol %
OPiv
23
O
PMBO
H
22
H
Grubbs' G-II
21
H
OPiv
OMe
H
13
11
O O
H
O O
O
OTBDPS
OPMB
C
OMe
Tol [0.01 M], rt
B
C
H
H
G-II =
Mes
H
N
N
CH3
Mes
Ph
32: BC-ring: 95% yield
25
Cl
Cl
Ru
PCy3
Scheme 6. Synthesis of BC-Ring 32 via Cyclic Acetal Tethered RCM.

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HETEROCYCLES, Vol. 86, No. 1, 2012
4.
Attempted Convergent Approach to C1-C23.
To examine the concept of connecting A-ring and BC-ring at C10 and C11 through a diastereoselective
aldol addition, and to explore a possibly more convergent route, we prepared aldehyde 33a19a,b and 33b.19c
By employing Mukaiyama's conditions,22 methyl ketone 11 was first converted to its respective TMS-enol
ether using LDA and TMSCl, and the resulting TMS-enol ether was added to aldehyde 33a [or 33b]
followed by the addition of a stoichiometric amount of BF3-Et2O at –78 oC to give the aldol product 34 in
72% yield with a diastereomeric ratio of 9:1 [Scheme 7]. The major isomer was initially assigned as the
desired C11,13-anti product based on Evans' non-chelation 1,3-asymmetric induction model.23 By using
aldehyde 33b under the same conditions, the yield for the respective aldol product 35 was comparable but
the dr was only 3:1. It is noteworthy that following Evans boron enolate conditions24 via di-n-butylboron
o
enolate derived from 11 and aldehyde 33a in CH2Cl2 at –78 C afforded 34 with 29% yield but in ~ 1:1
ratio.
LDA, TMSCl, THF, – 78 oC to 0 oC
and then BF3-Et2O, CH2Cl2, – 78 oC
H
H
H
H
9
PivO
O
Me
11
9
13
PivO
O
1
O
OP
O
O
OH OP
33a: P = TBS
33b: P = PMB
34: P = TBS: 72% yield; dr = 9 : 1
35: P = PMB: 60% yield; dr = 3 : 1
11
H
13
11
Me4NBH(OAc)3, AcOH
CH3CN, – 40 oC
PivO
PivO
H
H
H
H
13
13
9
11
9
11
O
O
OH OH OTBS
36: 72% yield; dr = 5 : 1
OH OH OPMB
37: 72% yield; dr = 5 : 1
p-TsOH, acetone
MS 4Å, rt
MeO OMe
DDQ, CH2Cl2
MS 4Å
PivO
OPiv
PivO
H
H
H
O
H
H
H
TBAF
CH2Cl2
13
9
11
13
13
9
11
9
11
O
O
OH
O
O
O
O
OH
O
O
OTBS
PMP
39: 90% yield
38: 93% yield
40: 60% yield
PivO
H
H
OH
only NOE
H
13
9
O
13
13
A-ring
H
11
11
11
O
O
OTBS
OTBS
H
9
9
O
H
O
O
O
H
H
H
A-ring
OMe
38': C9,11-syn acetonide
38: C9,11-anti acetonide
40
Scheme 7. Synthesis of Alcohol 39 and PMP-C11,13-Anti-Acetal 40.
A directed reduction of hydroxyl ketone 34 and 35 using Me4NBH(OAc)3 led to diols 36 and 37,
respectively. The diastereoselectivity here is modest with the dr being 5:1 for both diols 36 and 37, the

HETEROCYCLES, Vol. 86, No. 1, 2012
573
major isomer indeed favored C9 and C11 anti in relative stereochemistry. This anti-selectivity was
unambiguously confirmed through NOE experiments using C9,11-anti acetonide 38 that could be
prepared from C13-TBS-protected C9,11-anti-diol 36. To be ascertain, C9,11-syn acetonide 38’ was
also prepared in an analogous sequence to obtain a contrasting NOE outcome [Scheme 7].25 On the other
hand, by using C13-PMB-protected C9,11-anti-diol 37, we were able to finally unambiguously assign the
C11,13-anti relative stereochemistry through NOE of the corresponding PMP acetal 40, which could be
accessed via DDQ oxidation of 37.
PivO
OH
H
H
0.3 equiv Tf2NH, CH2Cl2, 4 Å MS
13
9
11
O
17
O
+
A
– 78 oC, 3 to 60 min
O
O
OH
OTBDPS
OMe OPiv
39
22b
PivO
PivO
H
H
1
1
O H
O H
A
OTBDPS
OPiv
OTBDPS
RCM
closing of B-ring
9
9
23
23
11
11
O
H
O
H
OPiv
OMe
13
13
O
O O
O
O O
B
C
17
OMe
41
42
Scheme 8. A Failed Convergent Approach to ABC-Ring 42 via Cyclic Acetal Tethered RCM of 41.
While syntheses of C9,11-anti acetonide 38 was quintessential in confirming key stereochemical
assignments, we were also attempting to explore a more convergent route to the Southern Half by first
connecting the A-ring and C-ring through cyclic acetal formation, linking first together C13-OH with C17.
However, that possibility did not work well. As shown in Scheme 8, attempted synthesis of vinyl cyclic
acetal 41 using alcohol 39 [via desilylation of 38] and lactol 22b was not successful under standard
conditions as well as other conditions. Thus, this thwarted our efforts to assembly the entire ABC
tricycle 42 through closing of the B-ring at the very end via the cyclic acetal tethered RCM strategy.
5.
Completing the Southern Macrocyclic Half.
To complete the synthesis of the Southern Half of the macrocycle G-ring, BC-ring 32 was transformed to
aldehyde 43 via removal of the PMB protecting group and SO3-Pyr/DMSO oxidation [Scheme 9]. To
connect the C10-C11 bond, aldehyde 43 was subjected to the same Mukaiyama aldol conditions21
employing TMS-enol ether derived in situ from methyl ketone 11. It was once again important here that
TMS-enol ether was first added to aldehyde 43 prior to the addition of a stoichiometric amount of

574
HETEROCYCLES, Vol. 86, No. 1, 2012
o
BF3-Et2O at –78 C. The aldol product 44 was obtained as a single isomer in 62% yield with C11-C13
relative stereochemistry assigned as anti based on the study described above in the preparation of 40.
OTBDPS
OPiv
OTBDPS
OPiv
PivO
PMBO
O
11
10
1) DDQ, CH2Cl2/H2O
H
H
H
H
+
O
11
O O
O O
A
2) SO3-Pyr, DMSO, Et3N
B
C
OTMS
B
C
OMe
OMe
32
43: 79% yield overall
OPiv
LDA, TMSCl
in THF
– 78 oC to 0 oC
3.0 equiv BF3-Et2O, CH2Cl2, -78 oC
A
O
OTBDPS
HO
11
13
H
10
9
H
H
OPiv
1
9
O O
PivO
O
Me
B
C
O
OMe
O
44: 62% yield; a single isomer
OPiv
11
OPiv
8.0 equiv Me4NBH(OAc)3
CH3CN, AcOH, – 30 oC
O
O
OTBDPS
OTBDPS
HO
HO
11
11
H
H
O O
9
9
OPiv
OMe
OPiv
OMe
O O
HO
HO
3 : 1
separable
46: 23% yield
OPiv
45: 68% yield
OPiv
1
1
A
C9,11-anti
C9,11-syn
O
O
0.30 equiv PPTS, acetone
MeO OMe
OTBDPS
OTBDPS
23
23
O
O
11
11
H
H
OPiv
OMe
OPiv
OMe
9
9
O O
O O
B
C
O
O
100.1 ppm
25.3 & 26.0 ppm
98.6 ppm
20.2 & 30.4 ppm
42: 85% yield
47: 90% yield
Scheme 9. A Successful Assembly of the Southern Macrocyclic Half.
This assignment is again also consistent with Evans non-chelation 1,3-asymmetric induction dipole
directed model.22 Directed reduction led to diols 45 and 46 with a 3:1 ratio in favor of the C9,11-anti
isomer. Although the selectivity was low, both isomers would sever a real purpose. Acetonide formation
of both anti and syn diol isomers 45 and 46 gave the desired C9,11-anti acetonide 42, and C9,11-syn
acetonide 47, respectively. With both syn and anti isomers in hand, we could unambiguously assign the
C9 and C11 relative stereochemistry in both 42 and 47 through the Rychnovsky-Evans C-13 analysis,26,27
thereby completing our endeavor in the assembly of the entire Southern macrocyclic Half of
(+)-spirastrellolide A.

HETEROCYCLES, Vol. 86, No. 1, 2012
575
CONCLUSION
We have described here details of our efforts toward the construction of both A-ring and BC-ring of
(+)-spirastrellolide A. The A-ring synthesis constituted a facile 12-step linear sequence starting from
1,5-pentanediol, and the BC-ring synthesis would ultimately showcase a cyclic acetal-tethered RCM
strategy that was developed in our lab for de novo synthesis of spiroketals. Assembly of the entire
Southern Half of this unique macrocycle would also require 1,3-anti-Mukaiyama aldol addition for
connecting A-ring and BC-ring specifically between C10 and C11, thereby culminating a successful and
practical 17-step approach linearly from (+)-2,3-(O)-iso-propylidene-L-threitol. An attempt toward an
even more convergent synthesis of the Southern Half was also carried out. However, our efforts failed in
connecting A-ring and C-ring through an acetal formation that would have linked together the free
C13-OH with C17 at the spiro-BC-ring junction. This cyclic acetal intermediate was to be subjected to
our cyclic acetal-tethered RCM strategy to close the B-ring. Nevertheless, the current 17-step approach
should prove to be highly practical for an ultimate total synthesis of (+)-spirastrellolide A.
EXPERIMENTAL
Synthesis of Allyl Alcohol 5.
To a slurry of NaH (9.22 g, 230 mmol) in anhyd THF was added dropwise 1,5-pentanediol at 0 °C. After
stirring this slurry for 30 min, benzyl bromide (25.6 mL, 211.2 mmol) was added. The reaction mixture
was refluxed for 12 h before being quenched with dropwise addition of H2O. The organic phase was
extracted with EtOAc, washed with sat aq NaCl, and dried over Na2SO4. The solvent was concentrated
under reduced pressure and the crude residue was purified by flash silica gel column chromatography
[33% EtOAc in hexane] to provide mono-benzylated diol as colorless oil (21.0 g) in 56% yield. Rf = 0.30
[33% EtOAc in hexane]; 1H NMR (500MHz, CDCl3) ! 1.41-1.48 (m, 2H), 1.58 (tt, J = 6.5, 6.5 Hz, 2H),
1.64 (tt, J = 7.0, 7.0 Hz, 2H), 2.02 (brs, 1H), 3.48 (t, J = 6.5 Hz, 2H), 3.62 (t, J = 7.0 Hz, 2H), 4.51 (s, 2H),
7.26-7.36 (m, 5H); 13C NMR (125MHz, CDCl3) ! 22.7, 29.7, 32.8, 63.1, 70.6, 73.2, 127.8, 127.9, 128.7,
138.8; IR (neat) cm-1 3393br, 3031s, 2936s, 2861s, 2360s, 2342s, 1455s, 1363s, 1098m; mass spectrum
(APCI): m/z (% relative intensity) 195 (M+H) + (75), 191 (8), 184 (9), 168 (10), 145 (19), 139 (15), 117
(30), 101 (100), 100 (51).
To a solution of oxalyl chloride (10.5 mL, 118 mmol) in CH2Cl2 was added a solution of DMSO (17
mL, 238.0 mmol) in CH2Cl2 at – 78 °C. After the addition, the mixture was stirred for 30 min. before the
above mono-benzylated diol (21.0 g, 108.0 mmol) was added to dropwise over 20 min period. The
mixture was stirred for an additional 1 h at –78 °C before Et3N (80.0 mL, 570.0 mmol) was added
through a syringe, and the mixture was slowly warmed up to rt. Subsequently, the reaction mixture was

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HETEROCYCLES, Vol. 86, No. 1, 2012
washed with H2O and sat aq NH4Cl. The organic phase was extracted with EtOAc, dried over Na2SO4,
and concentrated under reduced pressure. The crude residue was purified by flash silica gel column
chromatography [20% EtOAc in hexane] to aldehyde 4 as yellow oil (18.0 g) in 87% yield. Rf = 0.33
[20% EtOAc in hexane]; 1H NMR (400MHz, CDCl3) ! 1.59-1.67 (m, 2H), 1.68-1.76 (m, 2H), 2.42 (td, J
= 2.0, 7.2 Hz, 2H), 3.47 (t, J = 6.4 Hz, 2H), 4.51 (s, 2H), 7.24-7.35 (m, 5H), 9.72 (t, J = 2.0 Hz, 1H); 13C
NMR (125MHz, CDCl3) ! 19.2, 29.4, 43.8, 70.0, 73.2, 127.8, 127.9, 128.6, 138.7, 202.7; IR (neat) cm-1
2936s, 2860s, 1720s; mass spectrum (APCI): m/z (% relative intensity) 215 (M+Na)+ (11), 171 (8), 145
(41), 121 (20), 115 (55), 101 (100).
To a solution of aldehyde 4 (18.0 g, 94.0 mmol) in CH2Cl2 was added Wittig reagent Ph3P=CHCO2Et
(50.0 g, 141.0 mmol). After stirring at rt for 5 h, excess of CH2Cl2 was evaporated under reduced pressure
and the residue was diluted with a small amount of hexane. The slurry was filtered through a pad of
CeliteTM to remove triphenylphosphine oxide. The filtrate was concentrated under reduced pressure. The
crude residue was purified by flash silica gel column chromatography [10% EtOAc in hexane] to provide
Wittig olefination product as colorless oil (24.0 g) in 98% yield and !25:1 E:Z selectivity. Rf = 0.30
1
[10% EtOAc in hexane]; H NMR (400MHz, CDCl3) ! 1.27 (t, J = 7.0 Hz, 3H), 1.51-1.59 (m, 2H),
1.60-1.67 (m, 2H), 2.20 (ddt, J = 2.0, 7.2, 14.4 Hz, 2H), 3.46 (t, J = 6.0 Hz, 2H), 4.17 (q, J = 7.0 Hz, 2H),
4.50 (s, 2H), 5.81 (dt, J = 1.6, 15.6 Hz, 1H), 6.95 (dt, J = 6.8, 15.6 Hz, 1H), 7.24-7.36 (m, 5H); 13C NMR
(125 MHz, CDCl3) ! 14.6, 25.0, 29.5, 32.2, 60.4, 70.2, 73.2, 121.8, 127.8, 127.9, 128.7, 138.8, 149.2,
167.0; IR (neat) cm-1 2980m, 2937s, 2859s, 2360br, 1719s, 1654s; mass spectrum (APCI): m/z (%
relative intensity) 263 (M+H) + (7), 218(15), 217(100), 200(7), 199(52), 175(7), 171(10), 157(10).
To a solution of the above Wittig olefination product (24.0 g, 92.0 mmol) in THF was added DIBAL-H
(1.0 M in toluene, 239.0 mL, 230.0 mmol) at –78 °C. The mixture was gradually warmed up to –50 °C
and stirred for an additional 1.5 h before being quenched with aq HCl (1.0 M, 150 mL). The reaction
mixture was extracted with EtOAc, and combined organic layers was dried over Na2SO4 and concentrated
under reduced pressure. The crude residue was purified with flash silica gel column chromatography
[33% EtOAc in hexane] to provide allyl alcohol 5 (20.0 g) in 98 % yield. Rf = 0.35 [33% EtOAc in
hexane]; 1H NMR (400 MHz, CDCl3) ! 1.44-1.51 (m, 2H), 1.60-1.67 (m, 2H), 1.80 (s, 1H), 2.04-2.09 (q,
J = 7.2 Hz, 2H), 3.47 (t, J = 6.4 Hz, 2H), 4.08 (d, J = 4.0 Hz, 2H), 4.50 (s, 2H), 5.60-5.73 (m, 2H),
7.25-7.37 (m, 5H); 13C NMR (125 MHz, CDCl3) ! 26.0, 29.5, 32.2, 63.8, 70.4, 73.1, 127.8, 127.9, 128.6,
129.6, 132.9, 138.8; IR (neat) cm-1 3393brs, 2934s, 2858s, 2361s, 1455s, 1363s; mass spectrum (ESI):
m/z (% relative intensity) 243 (M+Na)+ (100),

HETEROCYCLES, Vol. 86, No. 1, 2012
577
Sharpless Asymmetric Epoxidation of Allyl Alcohol 5.
To a suspension of dried and pulverized Molecular Sieve 4Å in anhyd CH2Cl2 (6 mL) was added
D-(-)-di-isopropyl tartrate (0.051 mL, 0.24 mmol) followed by slow addition of Ti(Oi-Pr)4 (0.048 mL,
0.16 mmol) at –20 °C. After which the above allyl alcohol 5 (176.6 mg, 0.802 mmol) was added and the
mixture was stirred for 5 min. before TBHP (3.4 M, 0.71 mL, 2.40 mmol) was added slowly and the
resulting solution was stirred at – 20 °C for 1.5 h. The reaction was then quenched with aq NaOH (1.0 N)
and was stirred for an additional 1 h at 0 °C before it was warmed up to rt. The reaction mixture was
filtered through a pad of CeliteTM. The organic phase was extracted with CH2Cl2, dried over Na2SO4 and
concentrated under reduced pressure. The crude residue was purified by flash silica gel column
chromatography [50% EtOAc in hexane] to provide the desired epoxy alcohol 6 (164.4 mg) in 87% yield
and 96% ee. The enantiomeric excess was determined using chiral HPLC. The retention times of the
two enantiomers were 25.789 (S) min and 27.861 (R) min respectively. Rf = 0.10 [30% EtOAc in
23
1
hexane]; ["]D = 36.6 [c = 0.89, CH2Cl2]; H NMR (500 MHz, CDCl3) ! 1.42-1.60 (m, 4H), 1.60-1.69
(m, 2H), 2.20 (brt, J = 5.0 Hz, 1H), 2.91 (dt, J = 2.5, 4.0 Hz, 1H), 2.95 (dt, J = 2.5, 5.5 Hz, 1H), 3.49 (t, J
= 6.5 Hz, 2H), 3.62 (ddd, J = 4.5, 7.0, 11.5 Hz, 1H), 3.89 (ddd, J = 2.5, 5.5, 13.0 Hz, 1H), 4.51 (s, 2H),
7.28-7.30 (m, 1H), 7.30-7.35 (m, 4H); 13C NMR (125 MHz, CDCl3) ! 22.7, 29.5, 31.4, 56.0, 58.7, 61.9,
70.1, 72.9, 127.6, 127.7, 128.4, 138.5; IR (neat) cm-1 3434brs, 3030m, 2936s, 2861m, 1100s; mass
spectrum (APCI): m/z (% relative intensity) 237.2 (M+H)+ (100); m/z calcd for C14H20O3Na+ 259.1310,
found 259.1305.
Preparation of Acetonide 7.
To a solution of epoxy alcohol 6 (1.80 g, 7.50 mmol) in THF (10 mL) was added Red-Al (8.0 mL, 26.3
mmol) dropwise at –10 °C. The mixture was warmed up to rt and stirred for an additional 3 h.
Subsequently, sat aq NH4Cl (20 mL) was added and the resulting mixture was stirred for another 1 h. The
reaction mixture was extracted with Et2O, dried over Na2SO4, and concentrated under reduced pressure.
The crude residue was purified by flash silica gel column chromatography [91% EtOAc in hexane] to the
1
desired diol (1.76 g) in 98% yield. Rf = 0.33 [91% EtOAc in hexane]; H NMR (400MHz, CDCl3) !
1.39-1.57 (m, 4H), 1.59-2.04 (m, 4H), 2.81 (brs, 1H), 2.91 (brs, 1H), 3.50 (t, J = 6.4 Hz, 2H), 3.78-3.85
(m, 3H), 4.50 (s, 2H), 7.25-7.37 (m, 5H); 13C NMR (125MHz, CDCl3) ! 22.5, 29.9, 37.8, 38.5, 62.1, 70.6,
72.3, 73.2, 127.8, 128.0, 128.7, 138.8; IR (neat) cm-1 3366brs, 2933s, 2858s, 2360s, 2341s; mass
spectrum (ACPI): m/z (% relative intensity) 239 (M+H)+ (7), 221(17), 203(24), 185(12), 143(13), 131(16),
129(32), 117(7), 113(100), 111(9).
To a solution of the above diol (161.0 mg, 0.68 mmol) in acetone was added molecular sieve 4Å and

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HETEROCYCLES, Vol. 86, No. 1, 2012
dimethoxy-propane (0.25 mL, 2.03 mmol) followed by p-TsOH"H2O (12.8 mg, 0.068 mmol). The
mixture was stirred for 12 h before it was quenched with sat aq NaHCO3 (10 mL). The reaction mixture
was extracted with EtOAc, dried over Na2SO4, and concentrated under reduced pressure. The crude
residue was purified by flash silica gel column chromatography [17% EtOAc in hexane] to provide
acetonide 7 (170.9 mg) in 91% yield. Rf = 0.35 [17% EtOAc in hexane]; 1H NMR (400 MHz, CDCl3) !
1.38 (s, 3H), 1.38-1.43 (m, 2H), 1.44 (s, 3H), 1.46-1.58 (m, 4H), 1.63 (tt, J = 6.8, 6.8 Hz, 2H), 3.47 (t, J =
6.8 Hz, 2H), 3.82 (ddd, J = 1.6, 5.2, 12.0 Hz, 2H), 3.95 (td, J = 2.8, 12.4 Hz, 1H), 4.54 (s, 2H), 7.26-7.37
13
(m, 5H); C NMR (125 MHz, CDCl3) ! 19.5, 21.8, 29.9, 30.3, 31.5, 36.5, 60.3, 69.0, 70.5, 73.1, 98.4,
127.7, 127.9, 128.6, 138.9; IR (neat) cm-1 2992s, 2940s, 2862s, 2360s; mass spectrum (ESI): m/z (%
relative intensity) 301.7 (M+Na)+ (100); m/z calcd for C17H26O3Na+ 301.1780, found 301.1774.
Synthesis of Aldehyde 8
A suspension of acetonide 7 (587.5 mg, 2.10 mmol) and 10% Pd/C (45.0 mg) in EtOAc was stirred under
a balloon of hydrogen at rt for 1 h. The reaction mixture was filtered through a pad of CeliteTM and the
filtrate was concentrated under reduced pressure. The crude oil was used for the next step without further
1
purification. Rf = 0.50 [83% EtOAc in hexane]; H NMR (400MHz, CDCl3) ! 1.33 (s, 3H), 1.33-1.40
(m, 2H), 1.40 (s, 3H), 1.42-1.58 (m, 6H), 2.22 (brs, 1H), 3.58 (t, J = 6.4 Hz, 2H), 3.80-3.88 (m, 2H),
3.93-3.99 (td, J = 2.8, 12.0 Hz, 1H); 13C NMR (125MHz, CDCl3) ! 19.4, 21.4, 30.2, 31.5, 32.7, 36.3, 60.2,
62.7, 69.1, 98.4.
To a solution of the above crude alcohol in CH2Cl2/DMSO (2.5 mL, 10.6 mmol) were added Et3N (1.60
mL, 11.3 mmol) and SO3·pyridine complex (1.4 g, 8.5 mmol) at 0 °C. The resulting mixture was stirred at
0 °C for 1.5 h before it was quenched with H2O and extracted with CH2Cl2. The combined organic
layers were washed with sat aq NaCl, dried over Na2SO4, and concentrated under reduced pressure. The
crude residue was purified with flash silica gel column chromatography [33% EtOAc in hexane] to
1
provide aldehyde 8 (203.4 mg) in 52% yield. Rf = 0.45 [33% EtOAc in hexane]; H NMR (400 MHz,
CDCl3) ! 1.38 (s, 3H), 1.39-1.44 (m, 1H), 1.45 (s, 3H), 1.47-1.83 (m, 5H), 2.46 (td, J = 1.6, 6.4 Hz, 2H),
13
3.81-3.88 (m, 2H), 3.93-3.99 (td, J = 2.8, 12.0 Hz, 1H), 9.77 (t, J = 1.6 Hz, 1H); C NMR (125 MHz,
CDCl3) ! 18.0, 19.5, 30.2, 31.5, 36.0, 44.0, 60.2, 68.8, 98.5, 202.8; IR (neat) cm-1 3300m, 2993s, 2938s,
2869s, 1718s.
Preparation of A-Ring 11.
To a solution of aldehyde 8 (23.0 mg, 0.12 mmol) in THF (1 mL) was added Wittig reagent
Ph3P=CHCOMe (99.3 mg, 0.31 mmol) at rt and the mixture was refluxed for 5 h. The solution was then

HETEROCYCLES, Vol. 86, No. 1, 2012
579
cooled down to rt and concentrated under reduced pressure. The crude residue was purified with flash
column chromatography [33% EtOAc in hexane] to provide the desired E-enone (26.4 mg, 0.12 mmol) in
95% yield. Rf = 0.37 [33% EtOAc in hexane]; 1H NMR (400MHz, CDCl3) ! 1.38 (s, 3H), 1.39-1.43 (m,
2H), 1.45 (s, 3H), 1.46-1.79 (m, 6H), 2.25 (s, 3H), 3.81-3.88 (m, 2H), 3.96 (dt, J = 2.8, 12.0 Hz, 1H), 6.08
(dt, J = 1.6, 16.0 Hz, 1H), 6.80 (dt, J = 7.2, 16.0 Hz, 1H); 13C NMR (125MHz, CDCl3) ! 19.5, 23.8, 27.1,
30.3, 31.5, 32.6, 36.2, 60.2, 68.8, 98.5, 131.8, 148.3, 198.9; IR (neat) cm-1 3750m, 3675m, 3649m, 3629m,
2992s, 2940s, 2865s, 2340s, 1698s, 1673s, 1626s;
To a solution of the above E-enone (81.2 mg, 0.36 mmol) in CH2Cl2 was added p-TsOH·H2O (20.8 mg,
0.11 mmol) at 0 °C. The mixture was stirred for 1 h before it was quenched with sat aq NaHCO3. The
reaction mixture was extracted with CH2Cl2, and the combined organic layers were dried over Na2SO4 and
concentrated under reduced pressure. The crude residue was purified by flash silica gel column
chromatography [67% EtOAc in hexane] to provide pyran 10 (60.3 mg) as a colorless oil in 91% yield.
Rf = 0.33 [67% EtOAc in hexane]; 1H NMR (400 MHz, CDCl3) ! 1.17-1.35 (m, 2H), 1.51-1.65 (m, 4H),
1.66-1.76 (m, 1H), 1.81-1.87 (m, 2H), 2.16 (s, 3H), 2.47 (dd, J = 4.8, 16.0 Hz, 1H), 2.57 (brs, 1H), 2.67
(dd, J = 7.6, 16.0 Hz, 1H), 3.60 (dddd, J = 2.0, 3.6, 8.4, 12.8 Hz, 1H), 3.76 (dt, J = 5.6, 5.6 Hz, 2H), 3.83
13
(dddd, J = 2.0, 4.8, 8.0, 12.8 Hz, 1H); C NMR (125 MHz, CDCl3) ! 23.5, 31.1, 31.3, 31.4, 38.2, 50.3,
61.5, 74.2, 78.5, 207.5; IR (neat) cm-1 3852m, 3675m, 3649m, 3629m, 3376brs, 2934s, 2860s, 2340s,
1716s, 1670s; mass spectrum (APCI): m/z (% relative intensity) 187 (M+H) + (100), 169 (24), 151(27),
129(84), 111(18); mass spectrum (ESI): m/z calcd for C10H18O3Na+ 209.1154, found 209.1148.
To a solution of pyran 10 (60.3 mg, 0.32 mmol) in CH2Cl2 was added pyridine (0.11 mL, 1.30 mmol).
After stirring at rt for 0.5 h and pivaloyl chloride (0.08 ml, 0.65 mmol) was added. The mixture was
stirred for an additional 1 h before it was quenched with H2O. The organic phase was extracted with
CH2Cl2, dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified
with flash silica gel column chromatography [25% EtOAc in hexane] to provide A-ring 11 or the C1-C11
1
fragment (76.2 mg) as yellowish oil in 87% yield. Rf = 0.40 [25% EtOAc in hexane]; H NMR (400
MHz, CDCl3) ! 1.19 (s, 9H), 1.21 (m, 2H), 1.53-1.63 (m, 3H), 1.75 (dd, J = 7.0, 13.0 Hz, 2H), 1.82-1.85
(m, 1H), 2.18 (s, 3H), 2.41 (dd, J = 5.0, 15.0 Hz, 1H), 2.66 (dd, J = 7.5, 15.0 Hz, 1H), 3.42 (dddd, J = 1.5,
7.0, 10.5, 13.0 Hz, 1H), 3.75 (dddd, J = 2.0, 5.0, 8.0, 11.0 Hz, 1H), 4.12 (ddd, J = 6.0, 10.5, 11.0 Hz, 2H);
13C NMR (125 MHz, CDCl3) ! 23.7, 27.4, 31.2, 31.5, 31.6, 35.6, 39.0, 50.6, 61.3, 74.7, 178.7, 207.8 [one
carbon missing due to overlap]; IR (neat) cm-1 3420brs, 2929s, 2857s, 2360s, 2341s 1710s; mass
spectrum (APCI): m/z (% relative intensity) 271 (M+H)+ (100), 253 (71), 213 (85), 169 (50), 151 (89),
133(19), 129 (6), 111 (42); m/z calcd for C15H26O4Na+ 293.1729, found 293.1725.

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HETEROCYCLES, Vol. 86, No. 1, 2012
Synthesis Homo-Allyl Methyl Ether 13 from (+)-2,3-(O)-Iso-Propylidene-L-Threitol.
TBDPS-Silyl Protection. To a solution of commercially available (+)-2,3-(O)-iso-propylidene-L-threitol
o
(1.03 g, 6.30 mmol) in THF (30 mL) was added NaH (252.0 mg, 6.3 mmol) at –10 C. The mixture was
o
gradually warmed up to rt and stirred for 1 h before being cooled back down to –10 C and TBDPSCl
(1.77 mL, 6.90 mmol) was added. After 2 h at rt, the reaction was quenched with H2O (20 mL). The
organic solvent was evaporated and the aqueous fraction was extracted with CH2Cl2 (3 ! 20 mL). The
organic phases were combined, washed with sat aq NaCl, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The crude residue was purified by silica gel flash column chromatography
[gradient eluent: 8-25% EtOAc in hexane] to provide the desired TBDPS-silyl ether in 83% yield (2.09 g)
as yellow oil. Rf = 0.60 [30% EtOAc in hexane]; 1H NMR (300 MHz, CDCl3)! 1.09 (s, 9H), 1.42 (s, 3H),
1.45 (s, 3H), 2.00 (brds, 1H), 3.68 (dd, J = 11.7, 4.4 Hz, 1H), 3.76 (dd, J = 10.6, 6.2 Hz, 1H), 3.84 (dt, J =
9.7, 4.9 Hz, 2H), 4.03 – 3.95 (m, 1H), 4.12 (ddd, J = 12.1, 11.3, 5.7 Hz, 1H), 7.53 – 7.32 (m, 6H), 7.69 (t,
J = 6.1 Hz, 4H); mass spectrum (ESI): m/z (% relative intensity) 423.2 (M+Na)+ (100), 401.1 (M+H)+
(100); m/z calcd for C23H32O4SiNa+ 423.1968, found 423.1966.
SO3-Pyridine Oxidation.
To a solution of the above silyl ether (2.09 g, 5.20 mmol), anhyd DMSO
(7.38 mL, 104.0 mmol) and anhyd Et3N (3.62 mL, 25.9 mmol) in CH2Cl2 (21 mL) was added
SO3-pyridine (3.31 g, 20.8 mmol) at –10 oC. The solution was stirred at –10 oC for 2 h and was quenched
with H2O at -10 oC. The organic phase was separated and the aqueous fraction was extracted with CH2Cl2
(3 ! 20 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by silica gel flash column chromatography [gradient eluent:
10-30% EtOAc in hexane] to provide aldehyde 12 as colorless oil in 82% yield (1.69 g). 12: Rf = 0.35
[50% EtOAc in hexane]; 1H NMR (300 MHz, CDCl3) ! 1.09 (s, 9H), 1.45 (s, 3H), 1.52 (s, 3H), 3.84 (dd,
J = 4.2, 11.1 Hz, 4H), 3.90 (dd, J = 4.5, 11.1 Hz, 1H), 4.22 (dt, J = 4.2, 6.9 Hz, 1H), 4.48 (dd, J = 1.8, 7.2
Hz, 1H), 7.41-7.48 (m, 6H), 7.69-7.74 (m, 4H), 9.83 (d, J = 1.5 Hz, 1H).
Asymmetric Allylation of Aldehyde 12. To a solution of (-)-(Ipc)2BOMe (1.80 g, 5.69 mmol) in Et2O
o
(15 mL) was added allylmagnesium bromide (1.0 M in Et2O, 4.93 mL, 4.93 mmol) at 0 C. The solution
was warmed up to rt and stirred for an additional 1 h to give a white suspension. The suspension was
o
cooled to 0 C and allowed to settle for 0.5 h. The upper supernatant was transferred to a solution of
o
aldehyde 12 (1.51 g, 3.79 mmol) in ether (10 mL) via cannula at –78 C and the mixture was stirred at
o
o
–78 C for 3 h before it was quenched with aq NaOH (3.0 M, 20 mL) and 30% H2O2 (8 mL) at –78 C.
The mixture was reflux overnight. The organic phase was separated and the aqueous fraction was
extracted with Et2O (3 ! 20 mL). The combined organic phases were dried over Na2SO4, filtered, and

HETEROCYCLES, Vol. 86, No. 1, 2012
581
concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography
[gradient eluent: 10-20% EtOAc in hexane] followed by removing isopinocampheol (Ipc-OH) byproduct
through Kugelrohr distillation at 50 oC [1.0 mmHg] to provide the pure homoallyl alcohol as colorless oil
in 72% yield (1.20 g). Rf = 0.60 [25% EtOAc in hexane]; ["]D23 = - 3.83 [c 0.31, CHCl3]; 1H NMR (500
MHz, CDCl3) ! 1.09 (s, 9 H), 1.41 (s, 3H), 1.42 (s, 3H), 2.23 (ddd, J = 7.5, 7.5, 14.5 Hz, 1H), 2.41 (m,
1H), 2.52 (d, J = 3.0 Hz, 1H), 3.78 (m, 1H), 3.80 (d, J = 4.5 Hz, 2H), 3.82 (dd, J = 7.0, 7.0 Hz, 1H), 4.08
(ddd, J = 4.5, 4.5, 7.0 Hz, 1H), 5.15 (d, J = 10.5 Hz, 1H), 5.16 (d, J = 17.0 Hz, 1H), 5.92 (dddd, J = 7.0,
7.0, 10.5, 17.0 Hz, 1H), 7.41-7.44 (m, 6H), 7.70-7.72 (m, 4H); 13C NMR (125 MHz, CDCl3) ! 19.2, 26.8,
27.0, 27.1, 37.7, 64.7, 71.4, 79.1, 80.5, 109.0, 118.0, 127.8, 129.9, 132.9, 134.4, 135.7; IR (film) cm-1
3470 brs, 3072m, 2933s, 2859m, 1112s; mass spectrum (ESI): m/z (% relative intensity) 463.2 (M+Na)+
(100); m/z calcd for C26H36O4SiNa+ 463.2281, found 463.2275.
Methyl Ether Formation. To a solution of the above homoallylic alcohol (1.20 g, 2.72 mmol) in THF (14
mL) was added NaH (163.2 mg, 4.08 mmol) at –10 oC. The solution was warmed up to rt and stirred for
an additional 1 h before MeI (0.34 mL, 5.44 mmol) was added. The mixture was stirred at rt for 12 h and
quenched with H2O (15 mL). The organic phase was evaporated and the aqueous fraction was extracted
with CH2Cl2 (3 ! 20 mL). The combined organic phases were dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography
[gradient eluent: 2-3% EtOAc in hexane] to provide methyl ether 13 as colorless oil in 59% yield (725.0
mg). 13: Rf = 0.70 [16% EtOAc in hexane]; ["]D23 = - 7.54 [c 0.93, CHCl3]; 1H NMR (500 MHz, CDCl3)
! 1.10 (s, 9 H), 1.45 (s, 3H), 1.46 (s, 3H), 2.33-2.45 (m, 2H), 3.39 (s, 3H), 3.40 (m, 1H), 3.79 (dd, J = 4.0,
11.0 Hz, 1H), 3.90 (dd, J = 3.5, 11.0 Hz, 1H), 4.08 (dt, J = 4.0, 7.0 Hz, 1H), 4.12 (dd, J = 5.0, 8.0 Hz, 1H),
5.11 (d, J = 10.0 Hz, 1H), 5.15 (dd, J = 1.5, 17.0 Hz, 1H), 5.91 (ddt, J = 7.0, 10.0, 17.0 Hz, 1H),
13
7.40-7.45 (m, 6H), 7.73-7.76 (m, 4H); C NMR (125 MHz, CDCl3) ! 19.3, 26.9, 27.2, 27.3, 34.7, 58.1,
64.8, 77.9, 79.6, 81.5, 109.2, 117.2, 127.7, 129.7, 133.3, 134.6, 135.5; IR (film) cm-1 3072m, 2933s,
2861m, 1108s; mass spectrum (ESI): m/z (% relative intensity) 477.2 (M+Na)+ (100); m/z calcd for
C27H38O4SiNa+ 477.2432, found 477.2418.
Synthesis of Methoxy Aldehyde 14.
Hydroboration of Methyl Ether 13. To a solution of methyl ether 13 (91.6 g, 0.20 mmol) in THF (2
mL) was added 9-BBN (0.5 M, 0.81 mL, 0.4 mmol) at 0 oC. The solution was warmed up to rt and stirred
for 5 h before aq NaOH (3.0 M, 2 mL) and 30% H2O2 (1 mL) were added. The mixture was refluxed for 2
h. The organic phase was evaporated and the aqueous fraction was extracted with CH2Cl2 (3 ! 10 mL).
The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure.

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HETEROCYCLES, Vol. 86, No. 1, 2012
The residue was purified by silica gel flash column chromatography [gradient eluent: 30-40% EtOAc in
hexane] to provide the desired alcohol as colorless oil in 71% yield (66.9 mg). Rf = 0.30 [30% EtOAc in
hexane]; ["]D23 = -18.0 [c 0.75, CHCl3]; 1H NMR (500 MHz, CDCl3) ! 1.07 (s, 9H), 1.42 (s, 3H), 1.43 (s,
3H), 1.60-1.75 (m, 4H), 1.89 (brs, 1H), 3.35 (m, 1H), 3.39 (s, 3H), 3.64 (m, 2H), 3.76 (dd, J = 4.5, 10.5
Hz, 1H), 3.87 (dd, J = 3.7, 11.0 Hz, 1H), 4.01 (ddd, J = 4.0, 4.0, 8.0 Hz, 1H), 4.12 (dd, J = 5.0, 7.5 Hz,
13
1H), 7.38-7.41 (m, 6H), 7.69-7.72 (m, 4H); C NMR (125 MHz, CDCl3) ! 19.3, 26.6, 26.8, 27.1, 27.2,
28.5, 58.1, 62.9, 64.7, 78.0, 79.4, 81.6, 109.1, 127.7, 129.7, 133.3, 135.7; IR (film) cm-1 3425brs, 3072m,
2936s, 2864m, 1109s; mass spectrum (ESI): m/z (% relative intensity) 495.3 (M+Na)+ (100); m/z calcd for
C27H40O5SiNa+ 495.2537, found 495.2541.
SO3·Pyridine Oxidation.
To a solution of the above alcohol (66.9 mg, 0.14 mmol), anhyd DMSO
(0.20 mL, 2.82 mmol), and anhyd Et3N (0.11 mL, 0.79 mmol) in CH2Cl2 (2 mL) was added SO3·pyridine
(89.8 mg, 0.56 mmol) at –10 oC. The solution was stirred at –10 oC for 2 h and was quenched with H2O at
–10 oC. The organic phase was separated and the aqueous fraction was extracted with CH2Cl2 (3 ! 5 mL).
The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica gel flash column chromatography [gradient eluent: 5-15% EtOAc in
hexane] to provide aldehyde 14 as colorless oil in 99% yield (65.5 mg). 14: Rf = 0.70 [30% EtOAc in
hexane]; ["]D23 = - 23.5 [c 5.56, CHCl3]; 1H NMR (500 MHz, CDCl3) ! 1.08 (s, 9H), 1.42 (s, 6H), 1.92 (dt,
J = 7.0, 7.5 Hz, 2H), 2.54 (dt, J = 1.5, 7.0 Hz, 2H), 3.32 (s, 3H), 3.33 (m, 1H), 3.77 (dd, J = 4.5, 11.5 Hz,
1H), 3.87 (dd, J = 3.5, 11.0 Hz, 1H), 4.00 (ddd, J = 4.0, 4.0, 7.0 Hz, 1H), 4.10 (dd, J = 5.0, 12.0 Hz, 1H),
7.39-7.42 (m, 6H), 7.69-7.72 (m, 4H), 9.75 (s, 1H); 13C NMR (125 MHz, CDCl3) ! 19.3, 22.8, 26.8, 27.1,
27.2, 39.6, 58.0, 64.6, 77.7, 79.5, 80.8, 109.3, 127.7, 129.7, 133.2, 135.7, 202.1; IR (film) cm-1 3071m,
2935s, 2861m, 1726s, 1108s; mass spectrum (ESI): m/z (% relative intensity) 493.2 (M+Na)+ (100); m/z
calcd for C27H38O5SiNa+ 493.2386, found 493.2372.
Synthesis of Diol Enone 16 and Isolation of Bicyclic Acetal 18.
Vinyl Grignard Addition to Aldehyde 14. To a solution of aldehyde 14 (534.3 mg, 1.14 mmol) in Et2O
(10 mL) was added vinyl magnesium bromide (1.0 M in Et2O, 2.28 mL, 2.28 mmol) dropwise at –78 oC.
The solution was stirred for 3 h at –78 oC and quenched with sat aq NaHCO3 (10 mL). The organic phase
was separated and the aqueous fraction was extracted with Et2O (3 ! 10 mL). The combined organic
phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was
purified by silica gel flash column chromatography [gradient eluent: 15-20% EtOAc in hexane] to
provide allyl alcohol 15 as a mixture of diastereomers in 68% yield (385.2 mg). 15: Rf = 0.30 [25%
EtOAc in hexane]; 1H NMR (300 MHz, CDCl3) ! 1.08 (s, 9H), 1.43 (s, 6H), 1.63-1.81 (m, 4H), 1.90 (brs,

HETEROCYCLES, Vol. 86, No. 1, 2012
583
1H), 3.33 (m, 1H), 3.38 (s, 3H), 3.75 (dd, J = 4.5, 11.1 Hz, 1H), 3.88 (dd, J = 3.3, 11.1 Hz, 1H), 4.02 (ddd,
J = 4.2, 4.2, 8.1 Hz, 1H), 4.12 (dd, J = 7.2, 7.2 Hz, 2H), 5.11 (dd, J = 1.2, 10.5 Hz, 1H), 5.24 (dt, J = 17.1,
1.5 Hz, 1H), 5.88 (dddd, J = 1.6, 8.0, 11.5, 17.1 Hz, 1H), 7.36-7.45 (m, 6H), 7.69-7.74 (m, 4H); mass
spectrum (APCI): m/z (% relative intensity) 499.1 (M+H)+ (100); m/z calcd for C29H42O5SiNa+ 521.2699,
found 521.2694.
Removal of Acetonide. A solution of the above allylic alcohol (200.0 mg, 0.40 mmol) in mixture of
o
AcOH (5.60 mL) and H2O (2.40 mL) was heated to 70 C for 1.5 h. Then the solution was cooled to rt
and sat aq NaHCO3 was added slowly until pH is about 7. The mixture was diluted with EtOAc (20 mL).
Then organic solvents were separated and the aqueous fraction was extracted with EtOAc (3 ! 10 mL).
The combined organic phases were washed with sat aq NaCl, dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography
[gradient eluent: 40-60% EtOAc in hexane] to provide the pure triol intermediate in 86% yield (233.8
1
mg). Rf = 0.25 [50 % EtOAc in hexane]; H NMR (500 MHz, CDCl3) ! 1.08 (s, 9H), 1.54-1.80 (m, 4H),
2.75-2.95 (br, 3H), 3.38 (m, 1H), 3.38 (s, 3H), 3.67 (dt, J = 6.5, 1.5 Hz, 1H), 3.77 (dd, J = 5.5, 10.0 Hz,
1H), 3.81 (dd, J = 5.5, 10.0 Hz, 1H), 3.90 (dt, J = 1.0, 5.5 Hz, 1H), 4.13 (m, 1H), 5.09 (d, J = 10.5 Hz,
1H), 5.22 (dd, J = 17.5 Hz, 1H), 5.86 (dddd, J = 3.5, 6.0, 9.5, 16.5 Hz, 1H), 7.38-7.44 (m, 6H), 7.67-7.70
(m, 4H);13C NMR (125 MHz, CDCl3) ! 19.2, 25.5, 26.9, 32.0, 58.3, 66.2, 69.9, 71.7, 72.8, 82.2, 114.6,
127.9, 129.9, 132.8, 135.6, 141.1; IR (film) cm-1 3415brs, 3073m, 2935s, 2861m, 1109s; mass spectrum
(APCI): m/z (% relative intensity) 459.2 (M+H)+ (100); m/z calcd for C26H38O5SiNa+ 481.2386, found
481.2390.
MnO2 Oxidation and Formation of Bicyclic Acetal 18.
To a solution of the above triol (0.77 mmol)
in CH2Cl2 (10 mL) was added MnO2 (10.0 equiv 7.7 mmol) at rt. The solution was sonicated at rt for 6 h.
The mixture was filtered through CeliteTM and the residue was washed with CH2Cl2 several times. Then
the filtrate was collected and concentrated under reduced pressure. The residue was purified by silica gel
flash column chromatography [gradient eluent: 10-15% EtOAc in hexane] to provide diol enone 16,
which was used right away. To a solution of 16 (7.76 mg, 0.017 mmol) and 1,6-heptadiene-3-ol (3.90
mg, 0.034 mmol) in CH2Cl2 (0.5 mL) was added Tf2NH (0.1 M in CH2Cl2, 0.34 mL, 0.034 mmol) at –78
o
o
oC. The solution was stirred at –78 C for 5 min before quenched with Et3N (0.2 mL) at –78 C. The
mixture was warmed to rt and filtered through Celite.TM After concentrating the filtrate under reduced
pressure, the resulting crude residue (in 81% yield) showed a clean and pure NMR spectrum that could be
1
assigned as bicyclic acetal 18. 18: Rf = 0.70 [10% EtOAc in hexane]; H NMR (500 MHz, CDCl3)
! 1.07 (s, 9H), 1.93-1.95 (m, 4H), 3.42 (m, 1H), 3.46 (s, 3H), 3.54 (dd, J = 9.5, 9.5 Hz, 1H), 3.66 (dd, J =

584
HETEROCYCLES, Vol. 86, No. 1, 2012
5.0, 10.0 Hz, 1H), 3.99 (d, J = 5.0, 8.5 Hz, 1H), 4.65 (m, 1H), 5.20 (d, J = 11.0 Hz, 1H), 5.45 (d, J = 17.5
Hz, 1H), 5.87 (dd, J = 10.5, 17.5 Hz, 1H), 7.38-7.43 (m, 6 H), 7.64-7.66 (m, 4H); mass spectrum (APCI):
m/z (% relative intensity) 439.2 (M+H)+ (100); m/z calcd for C27H34O4SiNa+ 461.2124, found 461.2120.
Synthesis of Acid 20.
To a solution of aldehyde 14 (4.20 g, 8.90 mmol), 2-methyl-2-butene (4.7 mL, 44.5 mmol), and NaH2PO4
(2.46 g, 19.7 mmol) in the mixture of t-BuOH (30 mL) and H2O (15 mL) was added NaClO2 (3.22 g, 35.6
o
mmol) at –10 C in 3 portions. The solution was warmed up to rt and stirred for 1 h to give a pale green
solution. Then the reaction was quenched with sat aq Na2S2O3 (30 mL). The organic phase was separated
and the aqueous fraction was extracted with CH2Cl2 (3 ! 30 mL). The combined organic phases were
dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica
gel flash column chromatography [gradient eluent: 30-80% EtOAc in hexane] to provide the carboxylic
acid 20 as colorless oil in 98% yield (4.29 g). 20: Rf = 0.40 [50% EtOAc in hexane]; ["]D23 = - 15.9 [c
4.37, CHCl3]; 1H NMR (500 MHz, CDCl3) ! 1.08 (s, 9H), 1.42 (s, 6H), 1.86-1.94 (m, 2H), 2.49 (ddd, J =
7.0, 16.5, 16.5 Hz, 1H), 2.52 (ddd, J = 7.0, 16.5, 16.5 Hz, 1H), 3.37 (s, 3H), 3.38 (m, 1H), 3.77 (ddd, J =
1.5, 4.5, 11.5 Hz, 1H), 3.88 (ddd, J = 1.5, 4.0, 11.0 Hz, 1H), 4.02 (m, 1H), 4.11 (m, 1H), 7.38-7.43 (m,
6H), 7.70-7.73 (m, 4H), 11.1 (brs, 1H); 13C NMR (125 MHz, CDCl3) ! 19.3, 21.5, 25.1, 27.1, 27.2, 29.6,
58.2, 64.6, 77.8, 79.5, 80.6, 109.3, 127.7, 129.7, 133.2, 135.7, 179.5; IR (film) cm-1 3010brs, 3071m,
2934s, 2861m, 1710s, 1109s; mass spectrum (ESI): m/z (% relative intensity) 509.2 (M+Na)+ (100); m/z
calcd for C27H38O6SiNa+ 509.2330, found 509.2335.
Synthesis of Pival-Protected Lactone 21.
Lactone Formation. To a solution of acid 20 (4.20 g, 8.63 mmol) in CH2Cl2 (45 mL) was added
o
p-TsOH-H2O (4.92 g, 25.9 mmol) at 0 C. The solution was warmed up to rt and stirred for 3 h before
quenched with sat aq NaHCO3 (30 mL). The organic phase was separated and the aqueous fraction was
extracted with CH2Cl2 (3 ! 30 mL). The combined organic phases were dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography
[gradient eluent: 40-50% EtOAc in hexane] to provide the unprotected lactone as colorless oil in 83%
23
1
yield (3.08 g). Rf = 0.20 [50% EtOAc in hexane]; ["]D = 48.3 [c 5.24, CHCl3]; H NMR (300 MHz,
CDCl3) ! 1.09 (s, 9H), 1.82 (ddd, J = 3.9, 6.9, 12.9 Hz, 1H), 2.04-2.16 (m, 1H), 2.36 (dt, J = 18.6, 6.3 Hz,
1H), 2.55 (ddd, J = 17.1, 6.3, 6.3 Hz, 1H), 3.31 (s, 3H), 3.68 (dd, J = 6.0, 10.8 Hz, 1H), 3.79-3.85 (m, 2H),
13
3.90-3.97 (m, 1H), 4.46 (d, J = 6.0 Hz, 1H), 7.36-7.37 (m, 6H), 7.70-7.72 (m, 4H); C NMR (75 MHz,
CDCl3) ! 19.2, 20.8, 23.2, 26.8, 56.4, 63.9, 70.6, 72.9, 80.0, 127.7, 129.8, 133.0, 135.4, 170.9; IR (film)
cm-1 3440brs, 3071m, 2936s, 2861m, 1738s, 1110s; mass spectrum (ESI): m/z (% relative intensity) 451.2

HETEROCYCLES, Vol. 86, No. 1, 2012
585
(M+Na)+ (100); m/z calcd for C24H32O5SiNa+ 451.1911, found 451.1912.
Pivalation. To a solution of the above C22-unprotected lactone (805.7 mg, 1.88 mmol), pyridine (1.6 mL,
18.8 mmol) in CH2Cl2 (10 mL) was added (CH3)3COCl (0.46 mL, 3.8 mmol) followed by DMAP (45.9
mg, 0.38 mmol) at rt. The solution was stirred for overnight and quenched with H2O (10 mL). The
organic phase was separated and the aqueous fraction was extracted with CH2Cl2 (3 ! 10 mL). The
combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. The
residue was purified by silica gel flash column chromatography [gradient eluent: 10-20% EtOAc in
hexane] to provide the pivalate-protected lactone 21 as colorless oil in 77% yield (737.0 mg). 21: Rf =
0.65 [50% EtOAc in hexane]; ["]D23 = 26.8 [c 3.45, CHCl3]; 1H NMR (300 MHz, CDCl3) ! 1.08 (s, 9H),
1.24 (s, 9H), 2.06 (dddd, J = 5.1, 5.7, 9.0, 13.8 Hz, 2H), 2.46 (dt, J = 6.0, 17.0 Hz, 1H), 2.69 (ddd, J = 6.6,
9.0, 17.1 Hz, 1H), 3.39 (s, 3H), 3.42 (m, 1H), 3.88 (d, J = 6.6 Hz, 2H), 4.55 (dd, J = 2.4, 6.6 Hz, 1H),
5.33 (dt, J = 2.4, 6.6 Hz, 1H), 7.43-7.48 (m, 6H), 7.69-7.74 (m, 4H); 13C NMR (75 MHz, CDCl3) ! 19.0,
23.1, 26.6, 26.9, 27.0, 38.8, 56.7, 61.4, 71.3, 72.3, 78.6, 127.7, 129.7, 132.7, 135.4, 170.4, 177.5; IR
(film) cm-1 3071m, 2936s, 2862m, 1741s, 1151s; mass spectrum (APCI): m/z (% relative intensity) 513.3
(M+H)+ (100); m/z (ESI) calcd for C29H40O6SiNa+ 535.2486, found 535.2489.
Synthesis of Vinyl Ketone and Lactol Mixture 22a/b.
To a solution of the Piv-protected lactone 21 (131.2 mg, 0.256 mmol) in THF (2 mL) was added vinyl
o
magnesium bromide (1.0 M in THF, 0.51 mL, 0.51 mmol) dropwise at –78 C. The solution was stirred
for 1 h at –78 oC and quenched with sat aq NaHCO3 (5 mL) and diluted with CH2Cl2 (5 mL). The organic
phase was separated and the aqueous fraction was extracted with CH2Cl2 (3 ! 5 mL). The combined
organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue
was purified by silica gel flash column chromatography [gradient eluent: 15-20% EtOAc in hexane] to
provide an inseparable mixture of vinyl ketone and lactol 22a/b as colorless oil in 83% yield (114.7.0 mg)
and the recovered starting material (19.5 mg).
23
1
22a/b: Rf = 0.65 [50 % EtOAc in hexane]; ["]D = 9.79 [c 3.36, CHCl3]; H NMR (300 MHz, CDCl3)
! 1.05 (s, 9H), 1.25 (s, 9H), 1.45 (d, J = 2.7 Hz, 1H), 1.98-2.06 (m, 2H), 2.62-2.80 (m, 2H), 3.17-3.21 (m,
2H), 3.28 (s, 3H), 3.81 (m, 1H), 3.90 (d, J = 4.5 Hz, 2H), 5.29 (dt, J = 2.5, 7.0 Hz, 1H), 5.83 (d, J = 11.5
Hz, 1H), 6.24 (d, J = 18.0 Hz, 1H), 6.37 (dd, J = 11.0, 18.0 Hz, 1H), 7.40-7.48 (m, 6H), 7.68-7.71 (m,
4H); 13C NMR (75 MHz, CDCl3) ! 18.9, 22.3, 26.6, 27.1, 33.7, 38.9, 57.3, 64.1, 71.3, 78.9, 103.6, 127.7,
127.7, 128.1, 129.8, 129.8, 132.4, 132.6, 135.4, 135.5, 136.3, 177.6, 201.0; IR (film) cm-1 3506brs,
3071m, 2932s, 2858m, 1731s, 1112s; mass spectrum (ESI): m/z (% relative intensity) 563.3 (M+Na)+
(100); m/z calcd for C31H44O6SiNa+ 563.2799, found 563.2810.

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HETEROCYCLES, Vol. 86, No. 1, 2012
Synthesis of Vinyl Cyclic Acetal 25.
To a solution of the vinyl ketone and lactol mixture 22a/b (2.60 mg, 0.0048 mmol) in CH2Cl2 (0.1 mL)
was added MS 4Å (10.0 mg), alcohol 24 (4.80 mg, 0.019 mmol) followed by Tf2NH (0.5 M in toluene,
o
o
0.012 mL, 0.0024 mmol) at –78 C. The solution was stirred at –78 C for 2 min before quenched with
Et3N (0.05 mL) at –78 oC. The mixture was warmed to rt and filtered through Celite.TM After evaporating
the solvent under reduced pressure, the resulting crude residue was purified by silica gel flash column
chromatography [gradient eluent: 10-25% EtOAc in hexane] to provide the key vinyl cyclic acetal 25 in
56% yield based on starting material recovered. 25: Rf = 0.80 [25% EtOAc in hexane]; ["]D23 = 23.5 [c
1
0.46, CHCl3]; H NMR (300 MHz, CDCl3) ! 0.95 (d, J = 6.9 Hz, 3H), 1.04 (s, 9H), 1.28 (s, 9H),
1.37-1.59 (m, 3H), 1.71-1.81 (m, 2H), 1.91-2.00 (m, 2H), 2.90 (m, 1H), 3.23-3.28 (m, 2H), 3.32 (s, 3H),
3.69-3.75 (m, 2H), 3.81 (m, 1H), 3.83 (s, 3H), 4.04 (m, 1H), 4.07 (d, J = 11.5 Hz, 1H), 4.19 (d, J = 11.5
Hz, 1H), 4.87 (d, J = 17.1 Hz, 1H), 4.92 (d, J = 9.9 Hz, 1H), 5.18 (d, J = 12.9 Hz, 1H), 5.46 (d, J = 17.1
Hz, 1H), 5.59 (m, 1H), 5.67 (m, 1H), 5.78 (dd, J = 10.5, 17.1 Hz, 1H), 6.86 (d, J = 8.4 Hz, 2H), 7.14 (d, J
= 8.7 Hz, 2H), 7.38-7.43 (m, 6 H), 7.70-7.72 (m, 4H); 13C NMR (75 MHz, CDCl3) ! 15.4, 19.0, 23.0, 26.5,
27.3, 31.5, 34.8, 38.8, 40.3, 55.1, 56.2, 63.7, 66.4, 71.5, 71.8, 73.6, 74.4, 77.1 97.0, 113.5, 114.4, 115.8,
127.5, 127.6, 129.0, 129.5, 133.3, 135.5, 139.5, 140.5, 158.8, 170.4; IR (film) cm-1 3071m, 2932s, 2859m,
1731s, 1513m, 1112s; mass spectrum (ESI): m/z (% relative intensity) 795.6 (M+Na)+ (100); m/z calcd for
C46H64O6SiNa+ 795.4263, found 795.4251.
Minor Diene 26: Rf = 0.80 [25% EtOAc in hexane]; ["]D23 = 27.3 [c 0.40, CHCl3]; 1H NMR (300 MHz,
CDCl3) ! 1.07 (s, 9H), 1.24 (s, 9H), 2.16 (ddd, J = 3.0, 7.5, 17.7, 1H), 2.52 (ddd, J = 2.4, 2.4, 17.7 Hz,
1H), 3.40 (s, 3H), 3.47 (dt, J = 5.7, 7.5 Hz, 1H), 3.90 (d, J = 6.0 Hz, 2H), 4.18 (dd, J = 3.6, 7.5 Hz, 1H),
4.78 (brt, J = 4.2 Hz, 1H), 5.02 (d, J = 10.8 Hz, 1H), 5.38 (d, J = 17.1 Hz, 1H), 5.47 (dt, J = 3.6, 6.0 Hz,
1H), 6.07 (dd, J = 10.8, 17.1 Hz, 1H), 7.30-7.47 (m, 6 H), 7.70-7.73 (m, 4H); 13C NMR (75 MHz, CDCl3)
! 19.0, 22.4, 26.4, 26.5, 27.1, 56.5, 61.7, 70.4, 71.6, 74.5, 99.0, 112.7, 127.6, 129.6, 131.3, 133.1, 135.4,
149.9, 170.4; IR (film) cm-1 3069m, 2960s, 2856m, 1732s, 1279m, 1157s; mass spectrum (ESI): m/z (%
relative intensity) 545.3 (M+Na)+ (100); m/z calcd for C31H42O5SiNa+ 545.2694, found 545.2691.
Lactol 27.
1
Rf = 0.32 [50% EtOAc in hexane]; H NMR (500 MHz, CDCl3) ! 1.08 (s, 9H), 1.85 (m, 1H), 1.91 (m,
1H), 2.60 (ddd, J = 6.5, 9.0, 17.0 Hz, 1H), 2.71 (br, 1H), 2.73 (dddd, J = 6.0, 9.0, 17.0, 17.0 Hz, 1H), 3.28
(s, 3H), 3.38 (ddd, J = 4.5, 4.5, 8.5 Hz, 1H), 3.94 (ddd, J = 0.5, 5.0, 11.0 Hz, 1H), 3.61 (ddd, J = 3.5, 3.5,
7.5 Hz, 1H), 4.01 (ddd, J = 1.0, 3.5, 11.5 Hz, 1H), 4.53 (d, J = 11.5 Hz, 1H), 4.72 (d, J = 11.5 Hz, 1H),
5.80 (dd, J = 1.0, 10.5 Hz, 1H), 6.22 (d, J = 17.5 Hz, 1H), 6.35 (dd, J = 10.5, 17.5 Hz, 1H), 7.27-7.45 (m,

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13
11H), 7.72 (m, 4H); C NMR (125 MHz, CDCl3) ! 19.2, 22.7, 26.9, 57.1, 64.2, 70.9, 72.3, 76.9, 79.0,
80.2, 96.5, 127.6, 127.9, 128.4, 129.8, 133.0, 133.2, 135.6, 135.7, 136.6, 138.4; IR (film) cm-1 3459brs,
3069m, 2932s, 2859s, 1681m, 1428m, 1113s; mass spectrum (APCI): m/z (% relative intensity) 529.3
(M-H2O+H)+ (100); m/z calcd for C33H42O5SiNa+ 569.2699, found 569.2697.
Cyclic Acetal 29.
To a solution of lactol 27 (5.00 mg, 0.0094 mmol) in CH2Cl2 (0.1 mL) were added MS 4Å (10.0 mg),
3-butene-1-ol (6.77 mg, 0.094 mmol) followed by Tf2NH (2.64 mg, 0.0094 mmol) at –78 °C. The
o
solution was stirred at –78 C for 5 min before quenched with Et3N (0.1 mL) at –78oC. The mixture was
warmed to rt and filtered through CeliteTM. After evaporation of the solvent under reduced pressure, the
resulting crude residue was purified by flash column chromatography on silica gel [Gradient eluent: 2%
to 10% EtOAc in hexane] to provide cyclic acetal 29 in 89% yield (5.0 mg). Rf = 0.80 [25% EtOAc in
23
1
hexane]; ["]D = 28.9 [c 0.36, CHCl3]; H NMR (500 MHz, CDCl3) ! 1.06 (s, 9H), 1.45 (ddd, J = 4.0,
14.0, 14.0 Hz, 1H), 1.74 (ddd, J = 4.0, 14.0, 24.0 Hz, 1H), 1.88 (ddd, J = 4.0, 4.0, 14.0 Hz, 1H), 1.95
(dddd, J = 4.0, 4.0, 8.0, 8.0 Hz, 1H), 2.26 (m, 2H), 3.23 (s, 3H), 3.25 (ddd, J = 5.0, 10.5, 10.5 Hz, 1H),
3.37 (ddd, J = 7.0, 7.0, 9.5 Hz, 1H), 3.40 (ddd, J = 7.0, 7.0, 9.5 Hz, 1H), 3.76 (d, J = 9.5 Hz, 1H), 3.92 (m,
3H), 4.73 (d, J = 11.5 Hz, 1H), 4.79 (d, J = 11.5 Hz, 1H), 5.00 (dd, J = 11.0 Hz, 1H), 5.05 (d, J = 17.5 Hz,
1H), 5.17 (dd, J = 1.5, 11.0 Hz, 1H), 5.31 (dd, J = 2.0, 17.5 Hz, 1H), 5.70 (dd, J = 11.0, 17.5 Hz, 1H),
13
5.78 (ddt, J = 10.5, 17.5, 7.0 Hz, 1H), 7.27-7.41 (m, 11H), 7.70 (m, 4H); C NMR (125 MHz, CDCl3)
! 18.2, 24.1, 26.9, 34.0, 34.3, 56.0, 60.5, 64.5, 73.1, 73.6, 74.7, 80.9, 97.3, 116.2, 127.2, 127.6, 127.9,
128.2, 129.5, 133.6, 133.8, 135.6, 135.7, 138.8, 139.3; IR (film) cm-1 3071w, 2929s, 2857s, 1456m,
1104s; mass spectrum (ESI): m/z (% relative intensity) 623.3 (M+Na)+ (100); m/z calcd for C37H48O5SiNa+
623.3169, found 623.3172.
Cyclic Acetal 30.
23
1
Rf = 0.80 [25% EtOAc in hexane]; ["]D = 46.1 [c 0.33, CHCl3]; H NMR (500 MHz, CDCl3) ! 1.06 (s,
9H), 1.48 (ddd, J = 4.0, 13.0, 13.0 Hz, 2H), 1.65 (dddd, J = 4.0, 13.0, 13.0, 13.0 Hz, 2H), 1.81 (m, 2H),
1.95 (m, 2H), 2.29 (ddd, J = 6.0, 6.0, 6.0 Hz, 1H), 3.15 (ddd, J = 4.5, 10.5, 10.5 Hz, 1H), 3.21 (s, 3H),
3.39 (m, 5H), 3.49 (dd, J = 7.0, 14.0 Hz, 1H), 3.68 (d, J = 9.5 Hz, 1H), 3.92 (m, 4H), 4.74 (s, 2H), 5.00 (d,
J = 10.5 Hz, 1H), 5.02 (dd, J = 1.0, 11.0 Hz, 1H), 5.06 (d, J = 18.0 Hz, 1H), 5.07 (dd, J = 1.5, 17.5 Hz,
13
1H), 5.79 (ddt, J = 10.0, 17.0, 7.0 Hz, 2H), 7.27-7.41 (m, 11H), 7.69 (m, 4H); C NMR (125 MHz,
CDCl3) ! 19.2, 23.9, 26.9, 32.3, 34.2, 34.4, 36.1, 56.0, 59.2, 64.4, 66.7, 70.2, 73.1, 73.7, 74.8, 80.7, 98.0,
116.3, 116.4, 127.2, 127.6, 129.2, 129.5, 133.6, 133.8, 135.3, 135.5, 135.6, 139.2; IR (film) cm-1 3071m,
2931s, 2858s, 1428m, 1105s; mass spectrum (ESI): m/z (% relative intensity) 695.6 (M+Na)+ (100); m/z

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HETEROCYCLES, Vol. 86, No. 1, 2012
calcd for C41H56O6SiNa+ 695.3744, found 695.3740.
Diene 31.
Rf = 0.80 [25% EtOAc in hexane]; ["]D23 = -5.87 [c 0.92, CHCl3]; H NMR (300 MHz, CDCl3) ! 1.08 (s,
9H), 2.17 (t, J = 3.9 Hz, 2H), 3.40 (s, 3H), 3.74 (ddd, J = 3.0, 5.1, 10.2 Hz, 1H), 3.79 (ddd, J = 7.5, 7.5,
7.5 Hz, 1H), 3.93 (dd, J = 5.4, 11.4 Hz, 1H), 4.01 (dd, J = 3.3, 11.4 Hz, 1H), 4.35 (dd, J = 14.5, 6.9 Hz,
1H), 4.56 (d, J = 11.8 Hz, 1H), 4.71 (dd, J = 3.9, 3.9 Hz, 1H), 4.84 (d, J = 11.8 Hz, 1H), 4.97 (d, J = 10.8
1
13
Hz, 1H), 5.40 (d, J = 17.1 Hz, 1H), 6.01 (dd, J = 10.8, 17.1 Hz, 1H), 7.43 (m, 11H), 7.75 (m, 4H); C
NMR (75 MHz, CDCl3) ! 19.1, 24.0, 26.7, 56.4, 63.4, 71.6, 72.5, 73.9, 78.0, 99.4, 112.5, 127.5, 127.6,
127.8, 128.2, 129.5, 131.6, 133.3, 135.6, 138.3, 148.9; IR (film) cm-1 3070m, 2931s, 2858s, 1428m,
1112s; mass spectrum (APCI): m/z (% relative intensity) 529.2 (M+H)+ (100); m/z calcd for
C33H40O4SiNa+ 551.2594, found 551.2596.
BC-Ring 32 via RCM of Cyclic Acetal 25.
To a 0.01 M solution of cyclic acetal 25 (34.8 mg, 0.45 mmol) in toluene was added Grubbs Generation-II
Ru-catalyst (0.30 equiv) at rt and the mixture was stirred for 8 h until cyclic acetal 25 was consumed. The
suspension was concentrated under reduced pressure and the residue was purified with silica gel flash
column chromatography [isocratic eluent: 15% EtOAc in hexane] to provide C11-C23 fragment 32,
colorless oil, in 95% yield. The product yield was based on the amount of cyclic acetal compound 32 and
1
the ratio between cyclic acetal and side product was figured out by H NMR analysis. 32: Rf = 0.50 [20%
EtOAc in hexane]; ["]D23 = - 9.88 [c 0.24, CHCl3]; 1H NMR (500 MHz, CDCl3) ! 0.84 (d, J = 9.0 Hz, 3H),
1.02 (s, 9H), 1.26 (s, 9H), 1.52-1.75 (m, 4H), 1.85 (m, 1H), 2.00 (m, 2H), 2.94 (ddd, J = 2.5, 10.5, 10.5
Hz, 1H), 3.27 (s, 3H), 3.28-3.34 (m, 2H), 3.51 (ddd, J = 5.0, 9.0, 9.0 Hz, 1H), 3.57 (dd, J = 2.5, 9.5 Hz,
1H), 3.76 (ddd, J = 3.5, 10.5, 10..5 Hz, 1H), 3.79 (s, 3H), 3.92 (d, J = 9.0, 11.0 Hz, 1 H), 4.12 (d, J = 11.5
Hz, 1H), 4.16 (d, J = 11.5 Hz, 1H), 5.48 (dd, J = 2.5, 10.0 Hz, 1H), 5.54 (ddd, J = 3.0, 3.0, 8.5 Hz, 1H),
5.61 (dd, J = 1.5, 10.0 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.32-7.37 (m, 6 H),
7.67-7.68 (m, 4H); 13C NMR (125 MHz, CDCl3) ! 16.9, 19.4, 23.9, 26.9, 27.7, 33.3, 33.8, 34.5, 39.2, 55.5,
56.5, 64.3, 67.0, 71.2, 71.9, 72.7, 74.6, 93.5, 113.9, 127.8, 128.6, 129.7, 130.0, 130.9, 134.7, 135.9, 159.3,
177.8; IR (film) cm-1 3070m, 2959s, 2859m, 1731s, 1513m, 1101s; mass spectrum (ESI): m/z (% relative
intensity) 767.4 (M+Na)+ (100); m/z calcd for C44H60O6SiNa+ 767.3950, found 767.3947.
Mukaiyama Aldol Reaction
Silyl Enol Ether Formation Using 11. To a cooled solution of i-Pr2NH (41.6 µL, 0.294 mmol) in THF
(2 mL) was added n-BuLi (1.6 M in hexane, 172.0 µL, 0.274 mmol) at 0 oC. The solution was stirred for

HETEROCYCLES, Vol. 86, No. 1, 2012
589
10 min to give the LDA solution (0.5 M in THF) for next step. To the LDA solution was added pyran 11
via cannula at –78 oC and the mixture was stirred for 30 min. Chlorotrimethylsilane (35.0 µL.294 mmol)
was then added the lithium enolate and the reaction mixture was stirred for 30 min. The reaction mixture
o
was gradually warmed up to 0 C and was quenched with sat aq NaHCO3 solution (3 mL). The organic
phase was extracted with EtOAc, dried over Na2SO4, and concentrated under reduced pressure. The crude
trimethylsilyl enol ether was used for the next step without further purification.
Aldol Addition. To a cooled solution of the above trimethylsilyl enol ether (0.098 mmol) with either
aldehyde 33a [or 33b] (0.049 mmol) in CH2Cl2 (1 mL) was added BF3-Et2O (1.08 µL, 0.062 mmol) at
–78 oC dropwise. The reaction was stirred at –78 oC for 1 h before sat aq NaHCO3 (3 mL) was added to
quench the reaction. After the mixture was warmed up to room temperature, the organic phase was
separated and the aqueous fraction was extracted with CH2Cl2 (3 # 3 mL). The combined organic phases
were dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified with
flash silica gel column chromatography [25% EtOAc in hexane] to provide respective Mukaiyama-aldol
addition product 34 and 35. 34: For the major isomer: Rf = 0.65 [30% EtOAc in hexane]; 1H NMR (500
MHz, CDCl3) ! 0.08 (s, 3H), 0.11 (s, 3H), 0.90 (s, 9H), 0.99 (d, J = 7.0 Hz, 3H), 1.19 (s, 9H), 1.21 (m,
2H), 1.44 (dt, J = 3.0, 9.5 Hz, 2H), 1.49-1.61 (m, 4H), 1.74 (dd, J = 2.0, 13.0 Hz, 2H), 1.84 (m, 1H),
2.37-2.46 (m, 2H), 2.60 (m, 1H), 2.66 (dd, J = 8.0, 15.0 Hz, 1H), 3.20 (brd, J = 4.0 Hz, 1H), 3.38-3.42 (m,
1H), 3.75-3.80 (m, 1H), 3.94 (ddd, J = 4.0, 4.0, 8.0 Hz, 1H), 4.10 (ddd, J = 6.0, 11.0, 11.0 Hz, 1H), 4.13
(ddd, J = 7.0, 10.5, 10.5 Hz, 1H), 4.23 (ddd, J = 4.0, 8.0, 12.5 Hz, 1H), 5.01 (d, J = 9.0 Hz, 1H), 5.02 (d, J
13
= 18.0 Hz, 1H), 5.77 (ddd, J = 7.0, 10.0, 17.0 Hz, 1H); C NMR (125 MHz, CDCl3) ! -4.5, -4.7, 13.2,
17.3, 23.0, 25.5, 26.8, 27.3, 30.7, 30.9, 34.9, 39.6, 39.9, 43.0, 51.0, 60.9, 64.0, 71.8, 74.1, 74.5, 114.9,
140.6, 178.0, 209.6; IR (neat) cm-1 3751m, 2956s, 2936s, 2870s, 2342s, 1719s, 1702s; mass spectrum
(MALDI): m/z (% relative intensity) 535.5 (M+Na)+ (100); m/z calcd for C28H52O6SiNa+ 535.3431, found
535.3430. 35: For the major isomer: Rf = 0.20 [25% EtOAc in hexane]; 1H NMR (500 MHz, CDCl3) !
1.03 (d, J = 7.0 Hz, 3H), 1.19 (s, 9H), 1.20-1.32 (m, 2H), 1.48-1.61 (m, 6H), 1.73 (q, J = 6.5, 13.0 Hz, 2
H), 1.83 (m, 1H), 2.38 (dd, J = 5.0, 15.0 Hz, 1H), 2.56 (m, 2H), 2.64 (dd, J = 8.0, 15.0 Hz, 1H), 3.26 (d, J
= 3.5 Hz, 1H), 3.39 (dddd, J = 1.0, 6.5, 6.5, 12.5 Hz, 1H), 3.69 (dddd, J = 1.5, 4.0, 4.0, 8.0 Hz, 1H), 3.75
(m, 1H), 3.81 (s, 3H), 4.11 (ddd, J = 7.0, 7.0, 12.5 Hz, 2H), 4.26 (m, 1H), 4.51 (d, J = 10.5 Hz, 1H), 4.58
(d, J = 10.5 Hz, 1H), 5.03 (ddd, J = 1.5, 1.5, 7.5 Hz, 1H), 5.06 (ddd, J = 1.5, 1.5, 17.5 Hz, 1H), 5.81 (ddd,
13
J = 7.5, 10.5, 17.5 Hz, 1H), 6.87 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H); C NMR (125 MHz,
CDCl3) ! 14.1, 23.5, 27.3, 31.2, 35.4, 37.5, 38.8, 40.4, 50.1, 51.2, 55.4, 61.0, 64.8, 72.2, 74.4, 79.0, 113.9,
114.8, 129.6, 131.0, 140.8, 159.3, 178.6, 210.4; IR (neat) cm-1 3871m, 3751m, 3677m, 3651m, 3494brs,
2956s, 2936s, 2870s, 2342s, 1719s, 1702s, 1616s; mass spectrum (MALDI): m/z (% relative intensity)

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HETEROCYCLES, Vol. 86, No. 1, 2012
541(M+Na+) (100), 518 (M+) (4), 409 (4), 321 (10), 273 (39); m/z calcd for C30H46O7Na+ 541.3141, found
541.3144.
Directed Reduction for Synthesis of 1,3-Anti-Diols.
To a cooled solution of Me4NB(OAc)3H (26.0 mg, 0.099 mmol) in anhyd CH3CN (0.07 mL) was added
anhyd HOAc (0.07 mL) at rt. After stirring for 30 min, the solution was cooled to –30 oC and a solution of
the above ketone 34 or 35 (0.017 mmol) in CH3CN (0.5 mL) was added via cannula. The mixture was
stirred at –30 oC for 6 h before being warmed up to rt and stirred for another 6 h. After which, aq sodium
potassium tartrate solution (0.5 M, 1 mL) was added to the reaction followed by sat aq NaHCO3 (5 mL)
and CH2Cl2 (5 mL). The organic phase was separated and the aqueous fraction was extracted with CH2Cl2
(3 ! 3 mL). The combined organic phases were dried over Na2SO4 and concentrated under reduced
pressure. The crude residue was purified by flash silica gel column chromatography to provide the pure
respective 1,3-anti-diol 36 or 37. 36 with TBS protection: Rf = 0.40 [25% EtOAc in hexane]; 1H NMR
(400 MHz, CDCl3) ! 0.08 (s, 3H), 0.12 (s, 3H), 0.90 (s, 9H), 0.99 (d, J = 6.8 Hz, 3H), 1.20 (s, 9H),
1.41-1.69 (m, 10H), 1.75-1.85 (m, 4H), 2.37 (qdd, J = 0.8, 6.8, 12.8 Hz, 1H), 3.46 (dddd, J = 1.6, 6.0, 6.0,
13.2 Hz, 1H), 3.59 (dddd, J = 2.8, 2.8, 10.0, 10.0 Hz, 1H), 3.88 (br, 1H), 3.93 (ddd, J = 4.4, 4.4, 7.2 Hz,
1H), 4.00 (m, 1H), 4.06 (dddd, J = 2.8, 2.8, 10.0, 10.0 Hz, 1H), 4.13 (t, J = 6.0 Hz, 2H), 5.01 (dd, J = 0.8,
10.0 Hz, 1H), 5.02 (dd, J = 1.2, 11.6 Hz, 1H), 5.78 (ddd, J = 7.2, 10.4, 17.2 Hz, 1H); mass spectrum
(MALDI): m/z (% relative intensity) 537.5 (M+Na)+ (23); 515.5 (M+H)+ (100); m/z calcd for
C28H54O6SiNa+ 537.3587, found 537.3690. 37 with PMB protection: Rf = 0.35 [33% EtOAc in
1
hexane]; H NMR (500 MHz, CDCl3) ! 1.03 (d, J = 6.5 Hz, 3H), 1.19 (s, 9H), 1.21-1.35 (m, 2H),
1.46-1.62 (m, 6H), 1.65-1.72 (m, 2H), 1.75 (m, 2H), 1.82 (m, 1H), 2.60 (m, 1H), 3.32 (m, 1H), 3.59 (brdt,
J = 2.0, 7.0 Hz, 1H), 3.68 (dddd, J = 3.5, 5.0, 8.5, 12.0 Hz, 1H), 3.80 (s, 3H), 4.02 (m, 1H), 4.08 (m, 1H),
4.12-4.18 (m, 2H), 4.27 (m, 1H), 4.40 (dt, J = 7.5, 11.0 Hz, 1H), 4.48 (d, J = 11.0 Hz, 1H), 4.57 (d, J =
10.5 Hz, 1H), 5.03 (dd, J = 1.0, 11.5 Hz, 1H), 5.08 (dd, J = 1.5, 17.5 Hz, 1H), 5.41 (q, J = 5.0 Hz, 1H),
5.82 (ddd, J = 7.0, 10.5, 17.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H); 13C NMR (125
MHz, CDCl3) ! 14.1, 19.9, 25.4, 29.8, 33.7, 34.5, 37.5, 38.5, 39.8, 44.0, 55.0, 62.0, 66.5, 74.0, 75.5, 76.0,
79.9, 114.0, 115.0, 129.8, 131.4, 141.2, 159.9, 179.2; mass spectrum (MALDI): m/z (% relative intensity)
543.5 (M+Na)+ (100); m/z calcd for C30H48O7Na+ 543.3298, found 543.3301.
Standard Conditions as Described for the Acetonide Formation.
C13-TBS-Protected C9,11-Anti-Acetonide 38: Rf = 0.42 [10% EtOAc in hexane]; 1H NMR (400 MHz,
CDCl3) ! 0.09 (s, 6H), 0.89 (s, 9H), 0.99 (d, J = 8.5 Hz, 1H), 1.18 (s, 9H), 1.19 (m, 2H), 1.31 (s, 3H),
1.33 (s, 3H), 1.41 (m, 1H), 1.48-1.62 (m, 10H), 1.72-1.83 (m, 3H), 2.33 (m, 1H), 3.74 (m, 1H), 3.46 (m,

HETEROCYCLES, Vol. 86, No. 1, 2012
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1H), 3.76 (ddd, J = 5.0, 5.0, 9.5 Hz, 1H), 3.86 (m, 1H), 4.06 (m, 1H), 3.16 (m, 1H), 4.21 (m, 1H), 5.02
(dd, J = 2.5, 22.0 Hz, 1H), 5.03 (dd, J = 1.0, 14.5 Hz, 1H), 5.79 (ddd, J = 9.0, 15.0, 22.0 Hz, 1H);13C
NMR (100 MHz, CDCl3) ! 0.2, 14.5, 18.4, 23.9, 25.1, 25.6, 26.2, 27.4, 32.1, 35.2, 36.0, 38.9, 39.6, 40.5,
42.9, 43.6, 61.5, 62.9, 64.2, 72.6, 74.1, 74.7, 100.3, 114.8, 140.7, 179.6; mass spectrum (APCI): m/z (%
relative intensity) 555.4 (M+H)+ (100); m/z calcd for C31H58O6SiNa+ 577.3900, found 577.3895.
1
Standard TBAF-Desilylation Conditions. 39: Rf = 0.40 [25% EtOAc in hexane]; H NMR (400 MHz,
CDCl3) ! 1.05 (d, J = 6.8 Hz, 3H), 1.19 (s, 9H), 1.34 (s, 3H), 1.35 (s, 3H), 1.50-1.78 (m, 12H), 1.80-1.86
(m, 2H), 2.21 (dd, J = 6.8, 6.8 Hz, 1H), 2.75 (brs, 1H), 3.33 (m, 1H), 3.39 (m, 1H), 3.70 (m, 1H),
4.07-4.12 (m, 3H), 4.18-4.26 (m, 1H), 5.07 (d, J = 16.8 Hz, 1H), 5.08 (d, J = 11.2 Hz, 1H), 5.83 (ddd, J =
8.0, 11.6, 15.6 Hz, 1H); mass spectrum (APCI): m/z (% relative intensity) 441.1 (M+H)+ (100); m/z calcd
for C25H44O6Na+ 463.3036, found 463.3034.
1
Standard DDQ Conditions [See Below]. PMP-Acetal 40. Rf = 0.30 [25% EtOAc in hexane]; H
NMR (500 MHz, CDCl3) ! 1.08 (d, J = 7.0 Hz, 3H), 1.19 (s, 9H), 1.40-1.56 (m, 4H), 1.62-1.68 (m, 3H),
1.75-1.79 (m, 2H), 1.80-1.90 (m, 2H), 2.10 (m, 1H), 2.28 (m, 1H), 2.36 (m, 1H), 3.32 (ddd, J = 5.5, 5.5,
10.5 Hz, 1H), 3.45 (m, 1H), 3.61 (m, 1H), 3.79 (s, 3H), 3.86 (m, 1H), 4.04 (ddd, J = 5.5, 5.5, 11.0 Hz,
1H), 4.14 (ddd, J = 6.5, 6.5, 11.5 Hz, 1H), 4.20 (br, 1H), 4.37 (ddd, J = 7.0, 7.0, 11.0 Hz, 1H), 4.53 (q, J =
5.0 Hz, 1H), 5.05 (dd, J = 1.0, 9.5 Hz, 1H), 5.06 (dd, J = 1.0, 23.5 Hz, 1H), 5.72 (s, 1H), 5.91 (ddd, J =
8.0, 10.5, 25.0 Hz, 1H), 6.87 (d, J = 9.0 Hz, 2H), 7.41 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) !
15.5, 23.9, 27.5, 31.6, 36.0, 38.3, 39.0, 42.8, 43.4, 55.6, 61.0, 65.6, 70.1, 74.7, 75.5, 76.0, 94.3, 113.8,
115.1, 127.6, 132.1, 140.6, 160.0, 178.9; mass spectrum (APCI): m/z (% relative intensity) 519.3 (M+H)+;
m/z calcd for C30H46O7Na+ 541.3141, found 541.3145.
Synthesis of Aldehyde 43.
PMB Deprotected Via DDQ. To a solution of 32 (130.4 mg, 0.17 mmol) in CH2Cl2 : H2O (10:1) was
added DDQ (0.25 mmol, 1.5 equiv) at rt. After being stirred for 1.5 h, the mixture was quenched by sat aq
NaHCO3. The mixture was extracted with CH2Cl2, dried over MgSO4, filtered and concentrated in vacuo.
The residue was purified by silica gel flash column chromatography [gradient eluent: 33-50% EtOAc in
hexane] to provide the desired primary alcohol (94.8 mg, 0.15 mmol) in 88% yield as a colorless oil. Rf =
0.30 [33% EtOAc in hexane]; ["]D23 = + 3.50 [c 0.84, CH2Cl2]; 1H NMR (500 MHz, CDCl3) ! 0.87 (d, J =
9.0 Hz, 3H), 1.04 (s, 9H), 1.25 (s, 9H), 1.51-1.69 (m, 3H), 1.72-1.89 (m, 3H), 2.01-2.12 (m, 2H), 2.96
(ddd, J = 4.0, 10.0, 10.0 Hz, 1H), 3.25 (s, 3H), 3.45 (dt, J = 2.8, 9.6 Hz, 1H), 3.61 (t, J = 4.4 Hz, 2H),
3.69 (dd, J = 2.8, 9.6 Hz, 1H), 3.80 (dd, J = 4.4, 10.8 Hz, 1H), 3.88 (dd, J = 8.0, 10.8 Hz, 1H), 5.45 (ddd,

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J = 2.4, 4.4, 7.2 Hz, 1H), 5.49 (dd, J = 2.8, 10.0 Hz, 1H), 5.64 (dd, J = 2.0, 10.0 Hz, 1H), 7.32-7.37 (m, 6
H), 7.67-7.68 (m, 4H); 13C NMR (125 MHz, CDCl3) ! 16.8, 19.4, 24.0, 27.0, 27.6, 33.7, 34.2, 35.0, 39.2,
56.4, 60.1, 63.8, 71.6, 72.5, 72.7, 74.5, 93.8, 127.8, 128.6, 129.8, 133.9, 134.7, 135.9, 177.9; IR (neat)
cm-1 (neat) 3524w, 3073w, 2958s, 2933s, 2858brs, 2361s, 2342s, 1731s, 1699w, 1160s, 1107s; mass
spectrum (MALDI): m/z (% relative intensity) 647.3 (M+Na)+ (100); m/z calcd for C36H52O7SiNa+
647.3375, found 647.3352.
SO3·Pyridine Oxidation. To a solution of the above primary alcohol (94.8 mg, 0.15 mmol) in
DMSO/CH2Cl2 were added SO3·pyridine (96.8 mg, 0.61 mmol) and Et3N (0.12 mL, 0.76 mmol)
sequentially in this order at 0 ºC and the resulting mixture was stirred for 2 h at that temperature. The
residue was purified by silica gel flash column chromatography [isocratic: 25% EtOAc in hexane] to
provide C11-C23 fragment aldehyde 43 (101.2 mg, 0.132 mmol) in 90% yield. 43: Rf = 0.50 [25% EtOAc
in hexane]; ["]D23 = + 7.50 [c 0.24, CH2Cl2]; 1H NMR (400 MHz, CDCl3) ! 0.86 (d, J = 7.2 Hz, 3H), 1.04
(s, 9H), 1.24 (s, 9H), 1.55 (dd, J = 4.4, 13.2 Hz, 1H), 1.61-1.69 (m, 1H), 1.73 (ddd, J = 3.2, 3.2, 8.4, 1H),
1.98 (m, 1H), 2.07 (m, 1H), 2.37 (ddd, J = 3.2, 8.4, 16.0 Hz, 1H), 2.48 (ddd, J = 1.2, 3.6, 16.0 Hz, 1H),
2.96 (dt, J = 4.4, 10.0 Hz, 1H), 3.24 (s, 3H), 3.67 (dd, J = 2.4, 9.6 Hz, 1H), 3.77 (ddd, J = 3.6, 8.4, 9.6 Hz,
1H), 3.86 (dd, J = 4.0, 7.2 Hz, 2H), 5.47 (ddd, J = 2.8, 5.6, 8.0 Hz, 1H), 5.53 (dd, J = 2.8, 10.0 Hz, 1H),
5.64 (dd, J = 1.6, 10.0, Hz, 1H), 7.35-7.41 (m, 6H), 7.66-7.69 (m 4H), 9.61 (dd, J = 1.2, 3.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) ! 16.6, 19.5, 23.6, 27.1, 27.7, 33.7, 34.1, 39.2, 46.8, 56.4, 60.1, 69.7, 71.7, 72.0,
74.4, 93.9, 127.8, 128.9, 129.6, 129.8, 133.8, 135.8, 177.7, 201.1; IR (neat) cm-1 (neat) 3457w, 3074w,
2962s, 2935s, 2860brs, 2724w, 2362w, 2345w, 1733s, 1163s, 1108s; mass spectrum (MALDI): m/z (%
relative intensity) 645.3 (M+Na)+ (100); m/z calcd for C36H50O7SiNa+ 645.3218, found 645.3250.
Assembly of The C1-C23 Fragment 44.
Mukaiyama Aldol: To a cooled mixture of the silyl enol ether prepared as described above using pyran
11 (0.189 mmol) and aldehyde 43 (101.0 mg, 0.13 mmol) in CH2Cl2 (1 mL) was added BF3-Et2O (47.3
mL, 0.37 mmol) at –78 oC dropwise. The reaction was stirred at –78 oC for 1 h and then sat aq NaHCO3 (3
mL) was added to quench the reaction. After the mixture was warmed up to room temperature, the
organic phase was separated and the aqueous fraction was extracted with CH2Cl2. The combined organic
phases were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified with
silica gel flash column chromatography [gradient eluent: 2-10% EtOAc in hexane] to provide the desired
C1-C23 fragment 44 (62.4 mg, 0.069 mmol) in 62% yield (colorless oil) as a single isomer. 44: Rf = 0.50
[33% EtOAc in hexane]; ["]D23 = - 15.2 [c 0.43, CH2Cl2]; 1H NMR (500 MHz, CDCl3) ! 0.086 (d, J = 7.0
Hz, 3H), 1.02 (s, 9H), 1.18 (s, 9H), 1.24 (s, 9H), 1.40-1.47 (m, 1H), 1.50-1.71 (m, 8H), 1.72-1.80 (m, 4H),

HETEROCYCLES, Vol. 86, No. 1, 2012
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1.86 (m, 1H), 2.02 (m, 1H), 2.10 (dd, J = 2.5, 8.0 Hz, 1H), 2.42 (dd, J = 5.5, 16.0, 1H), 2.54 (d, J = 5.5
Hz, 1H), 2.65 (dd, J = 7.5, 15.5 Hz, 1H), 2.94 (ddd, J = 4.5, 10.0, 10.0 Hz, 1H), 3.03 (d, J = 3.0 Hz, 1H),
3.23 (s, 3H), 3.41 (dddd, J = 1.0, 7.5, 7.5, 7.5 Hz, 1H), 3.53 (td, J = 1.0, 8.0 Hz, 1H), 3.69 (dd, J = 2.0,
9.5 Hz, 1H), 3.76 (dddd, J = 5.5, 5.5, 5.5, 5.5 Hz, 1H), 3.86 (dd, J = 4.0, 11.0 Hz, 1H), 3.88 (dd, J = 4.0,
9.5 Hz, 1H), 4.12 (brd-t, J = 6.5 Hz, 2H), 4.24 (m, 1H), 5.45 (ddd, J = 2.0, 4.0, 4.0 Hz, 1H), 5.47 (dd, J =
2.5, 10.0 Hz, 1H), 5.63 (d, J = 10.0 Hz, 1H), 7.35-7.41 (m, 6H), 7.66-7.69 (m 4H); 13C NMR (125 MHz,
CDCl3) ! 16.9, 19.5, 23.7, 24.0, 27.1, 27.5, 27.7, 31.5, 31.6, 33.7, 33.9, 35.6, 39.0, 39.2, 39.3, 50.5, 51.2,
56.4, 61.3, 63.9, 64.3, 71.4, 71.7, 72.6, 74.4, 74.5, 74.9, 93.8, 127.8, 128.5, 129.7, 133.9, 134.8, 135.9,
178.0, 178.7, 209.4; IR (neat) cm-1 2957brs, 2933s, 2860brs, 2361s, 2342s, 1728s, 1157s; mass spectrum
(ESI): m/z (% relative intensity) 915.7 (M+Na)+ (80), 910.7 (60), 640.6 (50), 563.5 (100); m/z calcd for
C51H76O11SiNa+ 915.5055, found 915.5050.
Completion of Assembly of C9,11-Anti-Acetonide 42.
Directed Reduction. To a solution of tetramethylammonium triacetoxyborohydride (85.1 mg, 0.036
mmol) in anhyd acetonitrile (1.8 mL) and anhyd acetic acid (1.8 mL) at –30 ºC was added a solution of
ꢀ–hydroxy ketone 44 (40.5 mg, 0.045 mmol) in anhyd acetonitrile (1 mL). After the stirring for 12 h, the
reaction mixture was quenched with sat aq NaHCO3 with an additional stirring of 30 min. The mixture
was extracted with CH2Cl2. The combined organic layers are dried over Na2SO4, filtered, concentrated
under reduced pressure and the desired diol 45 [C9,11-anti] was isolated by silica gel flash column
chromatography [gradient eluent: 25-50% EtOAc in hexane]. However, the undesired diol 46 [C9,11-syn]
was also isolated. The combined yield was 91% with the anti:syn ratio being 3:1. The dr reflects the
isolated ratio. We tried to figure out the ratio according to the crude proton NMR but it was not clear by
integration.
23
1
C9,11-Anti-Diol 45: Rf = 0.40 [25% EtOAc in hexane]; ["]D = - 7.69 [c 0.52, CH2Cl2]; H NMR (400
MHz, CDCl3) ! 0.86 (d, J = 9.0 Hz, 3H), 1.02 (s, 9H), 1.19 (s, 9H), 1.23 (s, 9H), 1.45-1.60 (m, 10H),
1.63-1.70 (m, 3H), 1.72-1.80 (m, 5H), 1.85 (m, 1H), 2.02 (m, 1H), 2.18 (ddd, J = 2.0, 5.6, 5.6 Hz, 1H),
2.96 (ddd, J = 4.8, 4.8, 4.8 Hz, 1H), 3.22 (s, 3H), 3.35 (dddd, J = 6.0, 6.0, 11.6, 11.6 Hz, 1H), 3.56-3.61
(m, 2H), 3.77 (dd, J = 2.8, 9.6 Hz, 1H), 3.87 (d, J = 5.2 Hz, 1H), 3.88 (d, J = 6.8 Hz, 1H), 4.07 (ddd, J =
5.6, 5.6, 11.2 Hz, 1H), 4.14-4.22 (m, 2H), 4.32 (ddd, J = 6.0, 6.0, 10.8 Hz, 1H), 5.40 (ddd, J = 2.4, 5.2,
5.2 Hz, 1H), 5.48 (dd, J = 2.4, 10.0 Hz, 1H), 5.65 (dd, J = 2.0, 9.6 Hz, 1H), 7.34-7.40 (m, 6H), 7.66-7.68
13
(m, 4H); C NMR (125 MHz, CDCl3) ! 17.0, 19.5, 21.3, 23.9, 27.1, 27.5, 27.7, 31.5, 31.8, 33.4, 33.8,
35.9, 39.3, 39.5, 43.3, 44.6, 56.3, 60.7, 61.1, 63.6, 65.4, 65.8, 71.4, 71.9, 72.9, 74.6, 74.8, 75.7, 93.9,
127.8, 128.4, 129.8, 134.0, 135.0, 135.9, 178.0, 178.9; IR (neat) cm-1 2934 brs, 2859brs, 2361s, 2341s,
1728s, 1157s, 1105s; mass spectrum (MALDI): m/z (% relative intensity) 917.7 (M+Na)+ (100); m/z calcd

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HETEROCYCLES, Vol. 86, No. 1, 2012
for C51H78O11SiNa+ 917.5206, found 917.5192.
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1
C9,11-Syn-Diol 46: Rf = 0.50 [25% EtOAc in hexane]; ["]D = - 4.18 [c 0.41, CH2Cl2]; H NMR (500
MHz, CDCl3) ! 0.85 (d, J = 9.0 Hz, 3H), 1.02 (s, 9H), 1.19 (s, 9H), 1.24 (s, 9H), 1.40-1.90 (m, 18H), 2.02
(m, 2H), 2.92 (dt, J = 6.0, 12.5 Hz, 1H), 3.24 (s, 3H), 3.46-3.53 (m, 2H), 3.58 (m, 1H), 3.70 (dd, J = 3.5,
12.5 Hz, 1H), 3.91 (brd, J = 8.0 Hz, 2H), 3.97-4.03 (m, 2H), 4.15 (m, 1H), 4.17 (dd, J = 15.0, 15.0 Hz,
2H), 5.47 (br-dd, J = 2.4, 10.0 Hz, 2H), 5.64 (dd, J = 2.0, 10.0 Hz, 1H), 7.33-7.39 (m, 6H), 7.65-7.68 (m,
4H);13C NMR (125 MHz, CDCl3) ! 17.0, 19.4, 23.5, 23.9, 27.0, 27.4, 27.7, 31.3, 32.0, 34.0, 35.6, 38.9,
39.2, 41.0, 43.0, 56.4, 61.2, 64.1, 68.5, 70.1, 71.4, 71.7, 72.3, 72.6, 74.6, 75.2, 76.9, 79.0, 93.6, 127.7,
128.5, 129.7, 133.9, 134.8, 135.9, 178.5, 178.7; IR (neat) cm-1 2934 brs, 2859brs, 2361s, 2341s, 1728s,
1157s, 1105s; mass spectrum (MALDI): m/z (% relative intensity) 917.8 (M+Na)+ (100); m/z calcd for
C51H78O11SiNa+ 917.5206, found 917.5164.
Acetonide Protection. To a solution of C9,11-anti-diol 45 (18.3 mg, 0.021 mmol) in acetone (4.8 mL)
was added a catalytic amount of pyridinium p-toluene sulfonate (1.76 mg, 0.007 mmol) and
2,2-dimethoxypropane (10.0 µL, 0.063 mmol) and the resulting mixture was stirred over 1 h. The reaction
was quenched by sat aq NaHCO3 and the organic layer was extracted with CH2Cl2. The combined organic
layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The desired
C9,11-anti-acetonide 42 was isolated by silica gel flash column chromatography [gradient eluent: 20-50%
EtOAc in hexane] in 85% yield (15.7 mg, 0.018 mmol). Also, C9,11-syn-diol 46 (7.20 mg, 0.008
mmol) was transformed into the corresponding C9,11-syn-acetonide 47 using the same reaction protocol
in 90% yield (6.95 mg, 0.007 mmol).
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1
C9,11-Anti-Acetonide 42. Rf = 0.50 [20% EtOAc in hexane]; ["]D = - 2.70 [c 0.08, CH2Cl2]; H NMR
(400 MHz, CDCl3) ! 0.84 (d, J = 7.2 Hz, 3H), 1.00, (s, 9H), 1.10 (s, 3H), 1.11 (s, 3H), 1.19 (s, 9H), 1.26
(s, 9H), 1.37-1.60 (m, 8H), 1.60-1.95 (m, 9H), 1.98 (m, 1H), 2.90 (ddd, J = 4.4, 9.6, 9.6 Hz, 1H), 3.17 (s,
3H), 3.32 (ddd, J = 2.0, 10.0, 10.0 Hz, 1H), 3.35-3.39 (m, 1H), 3.44 (m, 1H), 3.57 (dd, J = 3.2, 9.6 Hz,
1H), 3.76 (dd, J = 2.8, 11.2 Hz, 1H), 3.92 (dd, J = 9.6, 11.2 Hz, 1H), 3.95-4.04 (m, 2H), 4.13 (ddd, J =
6.8, 6.8, 10.8 Hz, 1H), 4.22 (ddd, J = 6.8, 6.8, 10.4 Hz, 1H), 5.47 (dd, J = 2.4, 10.0 Hz, 1H), 5.52 (ddd, J
= 3.2, 3.2, 9.6 Hz, 1H), 5.58 (dd, J = 2.0, 10.0 Hz, 1H), 7.33-7.39 (m, 6H), 7.64-7.69 (m, 4H); 13C NMR
(125 MHz, CDCl3) ! 17.3, 19.4, 23.6, 23.9, 25.3, 26.0, 27.0, 27.5, 27.8, 32.1, 32.3, 33.9, 34.9, 36.0, 39.0,
39.2, 39.8, 42.0, 42.9, 56.2, 61.5, 62.7, 63.7, 64.5, 70.4, 71.9, 72.8, 74.1, 74.6, 74.7, 92.9, 100.1, 127.8,
128.5, 129.8, 133.8, 134.0, 136.0, 177.8, 178.7; IR (neat) cm-1 3454brs, 3048s, 2934s 2858m, 2363s,
2341s, 1661w, 1730s, 1284s, 1159s, 1106s, 1032s, 996s, 935s, 740s, 704s; mass spectrum (MALDI): m/z
(% relative intensity) 957.5 (M+Na)+ (100); m/z calcd for C54H81O11SiNa+ 957.5519, found 957.5507.
23
C9,11-Syn-Acetonide 47: Rf = 0.50 [20% EtOAc in hexane]; ["]D = + 2.54 [c 0.14, CH2Cl2]; H NMR
1