Stereoselective synthesis of (-)-PF1163A via prins cyclization

Article abstract of DOI:10.1055/s-0029-1219839

A highly stereoselective and convergent total synthesis of PF1163 A is described while proving the versatility of Prins cyclization in natural product synthesis. The Prins cyclization, Yamaguchi esterification, and ring-closing metathesis reactions are th

Full text of DOI:10.1055/s-0029-1219839

LETTER
1255
Stereoselective Synthesis of (–)-PF1163A via Prins Cyclization
S
tereosele
h
ctive
S
ynthe
i
sis of (–
l
)
-PF11
l
63A
v
u
ia Prins CyclizationS. Yadav,* M. Venkatesh, N. Thrimurtulu, Attaluri R. Prasad
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 14 December 2009
OH
O
Abstract: A highly stereoselective and convergent total synthesis
of PF1163 A is described while proving the versatility of Prins cy-
clization in natural product synthesis. The Prins cyclization,
Yamaguchi esterification, and ring-closing metathesis reactions are
the key steps utilized in the synthesis of macrolactone.
O
N
O
Keywords: (–)-PF1163A, 13-membered macrolactone, Prins cy-
clization, ring-closing metathesis
O
OH
O
R
I
O
PF1163A (1) and PF1163B (2) were isolated as new anti-
PF1163A (1), R = OH
PF1163B (2), R = H
N
fungal antibiotics from a fermentation broth of Penicilli-
um sp.1a and subsequently shown to be the first known
inhibitors of ERG25p, a C-4 methyl oxidase. The antifun-
gal activity of 1 is four times higher than that of 2 with
IC50 values of 12 ng/mL and 34 ng/mL, respectively.
PF1163A and B are structurally identical in every respect
except for the presence of an extra hydroxyl group in the
side chain of 1. Sasaki1b and co-workers elucidated the
structures after rigorous analysis of spectral and compar-
ative data. Tatsuta et al.2 realized a synthesis via asym-
metric allyl titanations thereby providing an absolute
proof for the stereostructures of the natural products 1 and
2. Inspired by the biological properties and structural sim-
ilarity to other biologically active natural products, such
as spongidepsin (3), doliculide (4), and the geodiamolides
(5, Figure 1) and in continuation of our interest in the syn-
thesis of bioactive naturally occurring lactones,4j,k we
have investigated the synthesis of (–)-PF1163A via Prins
cyclization.3
HO
N
H
O
doliculide (4)
O
N
Ph
R1
O
O
O
HN
O
O
X
O
O
N
spongidepsin (3)
HO
R2
geodiamolides 5
geodiamolide A (5a) R1 = R2 = Me, X = I
geodiamolide B (5b) R1 = R2 = Me, X = Br
Our retrosynthetic analysis (Scheme 1) revealed two key
synthons 16 and 17. With our initial focus on the synthesis
of synthon 16, we envisaged that the synthon 16 could be
achieved via Prins cyclization between known homoallyl-
ic alcohol 84c and aldehyde 95 (Scheme 1) whereas the
synthon 17 could be drawn from L-tyrosine.
Figure 1
in this approach. The primary hydroxyl group in 8 was
transformed to tosylate 9 using TsCl and triethylamine in
anhydrous CH2Cl2. The secondary hydroxyl group was
protected as its MOM ether 10 using MOMCl and
Hünig’s base in anhydrous CH2Cl2. Substitution of tosy-
late in 10 using NaI in acetone followed by reductive
opening of the iodomethyl pyran produced alcohol 12 in
91% overall yield (2 steps).4b,h The resulting secondary
hydroxyl group was protected as its TBS ether 13 using
TBSCl, DMAP, and imidazole. Treating 13 with Pd/C in
EtOAc furnished alcohol 14 accomplishing two reactions,
benzyl ether deprotection and the reduction of the double
bond in one pot. Oxidation of primary alcohol of 14 with
DMP in CH2Cl2 afforded the aldehyde, which was treated
without purification with methylene triphenylphospho-
rane to furnish olefin 15 in 88% overall yield. Finally
deprotection of the silyl protecting group using TBAF fur-
nished the key fragment 16 in 83% yield.
Our synthetic efforts began with the precurser building
block 6, which has been synthesized and utilized to make
several natural products in our group.4 Prins cyclization of
compound 6 with aldehyde 75 in the presence of TFA fol-
lowed by hydrolysis of the resulting trifluoroacetate gave
trisubstituted pyran 8 in 52% yield (Scheme 2). Though
the stereochemical aspects of such Prins cyclizations and
structurally similar compounds to 8 have been discussed
in detail previously,3,4 we decided to analyze the product
SYNLETT 2010, No. 8, pp 1255–1259
x
x.
x
x.
2
0
1
0
Advanced online publication: 16.04.2010
DOI: 10.1055/s-0029-1219839; Art ID: D36109ST
© Georg Thieme Verlag Stuttgart · New York

1256
J. S. Yadav et al.
LETTER
OH
O
OH
O
O
O
OH
OBn
OH
O
N
+
16
O
O
8
OBn
O
OH
tyrosine
OH
1
O
NBoc
OH
6
HO
17
Scheme 1 Retrosynthesis of (–)-PF1163A
OH
O
BnO
+
OH
O
a
BnO
OH
OH
7
8
6
OR
O
OMOM
d
OTs
I
BnO
BnO
b
O
11
9 R = H
10 R = MOM
c
OMOM
OR
OMOM
OTBS
e
g
BnO
HO
14
12 R = H
f
13 R = TBS
OH
MOMO
OTBS
MOMO
h
i
15
16
Scheme 2 Reagents and conditions: (a) aldehyde, TFA, CH2Cl2, 0 °C to r.t., 3 h then K2CO3, MeOH, r.t., 30 min, 52%; (b) (i) TsCl, Et3N,
CH2Cl2, 0 °C to r.t., 3 h, 85%; (c) MOMCl, DIPEA, CH2Cl2, 0 °C to r.t., 2 h, 92%; (d) NaI, acetone, reflux, 24 h, 90%; (e) Zn, EtOH, reflux,
2 h, 92%; (f) TBDMSCl, imidazole, DMAP, CH2Cl2, 0 °C to r.t., 2 h, 92%; (g) Pd/C, EtOAc, 8 h, 85%; (h) DMP, CH2Cl2, 2 h, 91%; then
Ph3P=CH2, THF; (i) TBAF, THF, 0 °C, 83%.
Fragment 17 was synthesized from L-tyrosine by a known palladium-catalyzed hydrogenation (Pd/C, EtOAc, H2, 8
route.6,7 The synthesis of the target compound was suc- h) provided the macrolactone 2111 in 75% yield over the
cessfully completed by combining the fragments 16 and two steps. Cleavage of the MOM ether was achieved us-
17 in a six-step sequence as shown in Scheme 3.
ing TFA in anhydrous CH2Cl2 at ambient temperature to
furnish PF1163A (1) in 75% yield. The synthetic com-
pound showed spectroscopic and analytical data {1H
NMR, 13C NMR, IR, Rf and [a]D} identical with those of
the natural compound.1
Fragment 16 was esterified with acid 17 under Yamaguchi
conditions8 to obtain ester 18 in 83% yield. Selective
deprotection of the NBoc group using TBSOTf, 2,6-luti-
dine, and TBAF9 gave the corresponding amine, which
was acylated with commercially available vinylacetic In summary, we have accomplished a highly convergent
acid using a combination of EDCI and HOBt to provide and stereoselective synthesis of PF1163A (1), thus prov-
the desired diene fragment 19 in 75% yield over the two ing the versatility of the Prins cyclization in natural prod-
steps. The ring-closing metathesis of diene 19 using 5 uct synthesis.
mol% Grubbs second-generation catalyst10 followed by a
Synlett 2010, No. 8, 1255–1259 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (–)-PF1163A via Prins Cyclization
1257
OBn
O
O
OBn
O
N
NBocMe
O
O
b,c
a
MOMO
O
16
MOMO
O
18
19
O
O
OBn
OBn
O
O
N
N
d
e
O
O
O
O
MOMO
MOMO
20
21
OH
O
O
N
f
O
O
OH
1
O
N
N
Mes
Mes
OH
Cl
Cl
Ph
Ru
B
PCy3
Mes = 2,4,6-Me3C6H2
Grubbs II
Scheme 3 Reagents and conditions: (a) Cl3C6H2COCl, DIPEA, 17, DMAP, toluene, 83%; (b) TBSOTf, 2,6-lutidine, TBAF, THF, r.t., 88%;
(c) EDCI, HOBt, CH2Cl2, then B; 75% (d) Grubbs II cat., CH2Cl2, reflux, 12 h, 65%; (e) Pd/C, H2, EtOAc, 8 h, 85%; (f) TFA–CH2Cl2 (1:5),
0 °C to r.t., 2 h, 75%.
Parker, G. D.; Willis, C. L. Org. Lett. 2003, 5, 2429.
(b) Yang, X.-F.; Mague, J. T.; Li, C.-J. J. Org. Chem. 2001,
66, 739. (c) Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew.
Chem. Int. Ed. 2005, 44, 3485. (d) Barry, C. S.; Bushby, N.;
Acknowledgment
M.V and N.T thank CSIR, New Delhi for the award of fellowships
and also thank DST for the financial assistance under J. C. Bose fel-
lowship Scheme.
Harding, J. R.; Willis, C. S. Org. Lett. 2005, 7, 2683.
(e) Cossey, K. N.; Funk, R. L. J. Am. Chem. Soc. 2004, 126,
12216. (f) Crosby, S. R.; Harding, J. R.; King, C. D.; Parker,
G. D.; Willis, C. L. Org. Lett. 2002, 4, 3407. (g)Marumoto,
References
S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky, S. D. Org. Lett.
2002, 4, 3919. (h) Kozmin, S. A. Org. Lett. 2001, 3, 755.
(i) Jaber, J. J.; Mitsui, K.; Rychnovsky, S. D. J. Org. Chem.
2001, 66, 4679. (j) Kopecky, D. J.; Rychnovsky, S. D.
J. Am. Chem. Soc. 2001, 123, 8420. (k) Rychnovsky, S. D.;
Thomas, C. R. Org. Lett. 2000, 2, 1217. (l) Rychnovsky, S.
D.; Yang, G.; Hu, Y.; Khire, U. R. J. Org. Chem. 1997, 62,
3022. (m) Su, Q.; Panek, J. S. J. Am. Chem. Soc. 2004, 126,
2425. (n) Yadav, J. S.; Reddy, B. V. S.; Sekhar, K. C.;
Gunasekar, D. Synthesis 2001, 885. (o) Yadav, J. S.; Reddy,
B. V. S.; Reddy, M. S.; Niranjan, N. J. Mol. Catal. A: Chem.
(1) (a) Nose, H.; Seki, A.; Yaguchi, T.; Hosoya, A.; Sasaki, T.;
Hoshoko, S.; Shomura, T. J. Antibiot. 2000, 53, 33.
(b) Sasaki, T.; Nose, H.; Hosoya, A.; Yoshida, S.;
Kawaguchi, M.; Watanabe, T.; Usui, T.; Ohtsuka, Y.;
Shomura, T.; Takano, S.; Tatsuta, K. J. Antibiot. 2000, 53,
38.
(2) Tatsuta, K.; Takano, S.; Ikeda, Y.; Nakano, S.; Miyazaki, S.
J. Antibiot. 1999, 52, 1146.
(3) For the Prins cyclization, see for example: (a) Barry, C. S.
J.; Crosby, St. R.; Harding, J. R.; Hughes, R. A.; King, C. D.;
Synlett 2010, No. 8, 1255–1259 © Thieme Stuttgart · New York

1258
J. S. Yadav et al.
LETTER
2004, 210, 99. (p) Yadav, J. S.; Reddy, B. V. S.; Reddy, M.
S.; Niranjan, N.; Prasad, A. R. Eur. J. Org. Chem. 2003,
1779.
72.4, 72.0, 68.5, 55.2, 38.0, 36.6, 34.4, 33.1, 32.5, 29.8, 21.5,
19.5. IR (KBr): nmax = 2922, 2852, 1456, 1362, 1037, 979
cm–1. ESI-MS: m/z = 521 [M+ + H], 543 [M+ + Na].
(4S,6S,9R)-4-(Methoxymethoxy)-9-methyldodec-11-en-
6-ol (16)
(4) (a) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A. R.
Tetrahedron Lett. 2006, 47, 4397. (b) Yadav, J. S.; Reddy,
M. S.; Prasad, A. R. Tetrahedron Lett. 2006, 47, 4937.
(c) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron
Lett. 2005, 46, 2133. (d) Yadav, J. S.; Reddy, M. S.; Prasad,
A. R. Tetrahedron Lett. 2006, 47, 4995. (e) Yadav, J. S.;
Reddy, M. S.; Rao, P. P.; Prasad, A. R. Synlett 2007, 2049.
(f) Yadav, J. S.; Rao, P. P.; Reddy, M. S.; Rao, N. V.; Prasad,
A. R. Tetrahedron Lett. 2007, 48, 1469. (g) Yadav, J. S.;
Kumar, N. N.; Reddy, M. S.; Prasad, A. R. Tetrahedron
2006, 63, 2689. (h) Rao, A. V. R.; Reddy, E. R.; Joshi, B. V.;
Yadav, J. S. Tetrahedron Lett. 1987, 28, 6497. (i) Yadav, J.
S.; Sridhar Reddy, M.; Rao, P. P.; Prasad, A. R. Synlett 2007,
2049. (j) Yadav, J. S.; Hissana, A.; Gayathri, K. U.; Rao, N.
V.; Prasad, A. R. Synthesis 2008, 3945. (k) Yadav, J. S.;
Thrimurtulu, N.; Uma Gayathri, K.; Reddy, B. V. S.; Prasad,
A. R. Tetrahedron Lett. 2008, 49, 6617.
To a stirred soln of 15 (0.8 g, 2.15 mmol) in anhyd THF (8
mL), TBAF (4.3 mL, 4.3 mmol) was added, and the mixture
was stirred at 0 °C for 2 h. The reaction mixture was
quenched with H2O (5 mL) and extracted with EtOAc (2 × 5
mL), and the combined organic layers washed with brine (10
mL), dried over anhyd Na2SO4, and concentrated under
reduced pressure to remove the solvent. The crude residue
was then purified by column chromatography on silica gel
(EtOAc–hexane, 1:9) to afford 16 as a white solid; yield 0.46
20
g (83%); clear oil; Rf = 0.4 (EtOAc–hexane, 2:8); [a]D
+12.1 (c 0.9, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 5.85–5.70 (m, 1 H), 5.05–4.94 (m, 2 H), 4.76–4.62 (m, 2
H), 3.90–3.76 (m, 2 H), 3.40 (s, 2 H), 2.13–2.02 (m, 1 H),
1.96–1.84 (m, 1 H), 1.68–1.08 (m, 10 H), 0.99–0.84 (m, 6
H). 13C NMR (75 MHz, CDCl3): d = 137.5, 115.5, 96.2,
75.9, 68.2, 55.8, 41.2, 41.1, 37.0, 34.9, 32.9, 32.4, 19.4, 18.7,
14.1. IR (KBr): nmax = 3453, 2930, 1459, 1376, 1038, 911
cm–1. ESI-MS: m/z = 281 [M+ + Na].
(5) Aldehyde 9 was prepared from (R)-citronellol in two steps in
76% overall yield as shown in Scheme 4.
(2S)-(4S,6S,9R)-4-(Methoxymethoxy)-9-methyldodec-
11-en-6-yl 3-{4-[2-(benzyloxy)ethoxy]phenyl}-2-(N-
Methylbut-3-enamido) Propanoate (19)
a) NaH
HO
BnBr, THF
BNO
O
b) O3
To a stirred solution of N-Boc-deprotected amine (200 mg,
0.35 mmol) in anhyd CH2Cl2 (12 mL) was added carboxylic
acid fragment B (33 mg, 0.38 mmol) and then HOBt (4 mg,
0.035 mmol) followed by EDCI (201 mg, 1.05 mmol). The
reaction was stirred for 6 h at r.t., quenched with HCl (1 N,
15 mL), and diluted with Et2O (20 mL). The aqueous layer
was extracted with Et2O (20 mL), and the resulting solution
washed with brine (10 mL), dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was
purified by silica gel chromatography (EtOAc–hexane, 3:7)
to afford diene 2 as a colorless oil (160 mg, 75%). Rf = 0.4
(EtOAc–hexane, 3:7); [a]D20 –9.3 (c 0.5,CHCl3). 1H NMR
(300 MHz, CDCl3): d = 7.36–7.23 (m, 5 H), 7.11–7.01 (m, 2
H), 6.86–6.77 (m, 2 H), 5.85–5.65 (m, 2 H), 5.35–5.27 (m, 1
H), 5.11–4.90 (m, 4 H), 4.64–4.44 (m, 4 H), 4.13–4.06 (m, 2
H), 3.82–3.76 (m, 2 H), 3.51–3.39 (m, 1 H), 3.36–3.18 (m, 4
H), 3.14–2.86 (m, 4 H), 2.82 (s, 3 H), 2.10–1.96 (m, 1 H),
1.94–1.80 (m, 1 H), 1.67–1.19 (m, 11 H), 0.95–0.82 (m, 6
H). 13C NMR (75 MHz, CDCl3): d = 171.1, 169.5, 157.6,
137.1, 131.0, 129.8, 129.1, 128.4, 127.7, 117.7, 115.9,
114.9, 114.6, 96.2, 74.5, 73.4, 72.8, 68.5, 67.3, 57.8, 55.8,
41.3, 39.2, 38.9, 37.4, 33.9, 32.7, 32.3, 31.6, 29.8, 19.4, 18.2,
14.3. IR (KBr): nmax = 2924, 2856, 1650, 1243, 1046 cm–1.
ESI-MS: m/z = 660 [M+ + Na].
(3S,10R,13S)-3-[4-(2-hydroxyethoxy)benzyl]-13-S-2-
(methoxymethoxy)pentyl-4,10-dimethyl-1-oxa-4-
azacyclotridecane-2,5-dione (21)
To solution of compound 20 (0.200 g, 0.328 mmol) in
EtOAc (10 mL) was added Pd/C 10% (50 mg) and the
mixture stirred under H2 atmosphere for 7 h. After
completion, the reaction mass was filtered through Celite,
and the solvent was removed under reduced pressure to give
crude product 21. Purification using column chromatog-
raphy on silica gel (hexane–EtOAc, 4:1) gave pure product
as a colorless solid (0.145 g, 85% yield); [a]D25 –48.5 (c 0.5,
CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.22–7.07 (m, 2
H), 6.83 (d, 2 H, J = 8.5 Hz), 5.13–5.02 (m, 1 H), 4.66–4.39
(m, 2 H), 4.08–4.02 (m, 2 H), 3.97–3.90 (m, 2 H), 3.35 (s, 3
H), 3.23–3.11 (t, 1 H, J = 11.1 Hz), 3.07–2.91 (m, 3 H),
2.88–2.57 (m, 1 H), 2.26–2.07 (m, 1 H), 1.72–1.08 (m, 19
H), 0.92–0.89 (m, 2 H), 0.85 (t, 3 H, J = 6.8 Hz), 0.81 (d, 3
TPP, CH2Cl2
–78 to 0 °C
76% (2 steps)
7
Scheme 4
(6) Bouazza, F.; Renoux, B.; Bachmann, C.; Gesson, J.-P. Org.
Lett. 2003, 5, 4049.
(7) Boger, D. L.; Yohannes, D. J. Org. Chem. 1988, 53, 487.
(8) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi,
M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
(9) (a) Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870.
(b) Chandrasekhar, S.; Yaragorla, S. R.; Sreelakshmi, L.;
Reddy, C. h. R. Tetrahedron 2008, 64, 5174.
(c) Chandrasekhar, S.; Yaragorla, S. R.; Sreelakshmi, L.
Tetrahedron Lett. 2007, 48, 7339.
(10) (a) Scholl, M.; Ding, S.; Lee, C.; Grubbs, R. H. Org. Lett.
1999, 1, 953. (b) Chatterjee, A. K.; Morgan, J. P.; Scholl,
M.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 3783.
(11) {(2S,4R)-6-[(R)-5-(Benzyloxy)-3-methylpentyl]-
tetrahydro-4-(methoxymethoxy)-2H-pyran-2-yl} Methyl
4-Methylbenzenesulfonate (10)
To a stirred solution of alcohol 9 (1.8 g, 3.78 mmol) in anhyd
CH2Cl2 (20 mL) at 0 °C were added DIPEA (1.31 mL, 7.56
mmol), DMAP (cat.) and MOMCl (0.91 g, 11.34 mmol)
successively, the resulting mixture was stirred for 3 h at r.t.
and then quenched by adding H2O (10 mL) and extracted
with CH2Cl2 (3 ´ 20 mL). The organic extracts were washed
with brine (10 mL), dried over anhyd Na2SO4, and
concentrated under reduced pressure to remove the solvent,
and the crude residue was purified by column
chromatography to afford the pure product 10 as a liquid
(1.80 g, 92%). Rf = 0.7 (SiO2, 10% EtOAc in hexane); clear
oil; Rf = 0.5 (EtOAc–hexane, 3:7). [a]D20 –2.6 (c 1.15,
CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.82–7.76 (m, 2
H), 7.38–7.22 (m, 7 H), 4.66 (s, 2 H), 4.49 (s, 2 H), 4.14–3.92
(m, 2 H), 3.73–3.61 (m, 1 H), 3.59–3.43 (m, 3 H), 3.35 (s, 3
H), 3.25–3.14 (m, 1 H), 2.43 (s, 3 H), 1.98–1.88 (dd, 2 H,
J = 9.4, 2.8 Hz), 1.78–1.01 (m, 10 H), 0.87 (d, 3 H, J = 6.4
Hz). 13C NMR (75 MHz, CDCl3): d = 144.6, 138.6, 132.9,
129.7, 128.3, 127.9, 127.5, 127.4, 94.3, 76.1, 72.8, 72.5,
Synlett 2010, No. 8, 1255–1259 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (–)-PF1163A via Prins Cyclization
1259
H, J = 6.2 Hz). 13C NMR (75 MHz, CDCl3): d = 169.9,
reduced pressure. The residue was purified by silica gel
chromatography (EtOAc–hexane, 3:7) to afford 1 as a
colorless oil (13 mg, 75%). Rf = 0.4 (EtOAc–hexane, 7:3);
[a]D20 –88.5 (c 1.0, MeOH). 1H NMR (200 MHz, CDCl3):
d = 7.20–7.03 (m, 2 H), 6.84–6.75 (m, 2 H), 5.82–5.66 (m, 1
H), 5.14–4.91 (m, 1 H), 4.01 (s, 1 H), 3.90 (s, 1 H), 3.53–3.27
(m, 2 H), 3.01–2.80 (m, 3 H), 2.78–2.52 (m, 1 H), 2.38–2.24
(m, 1 H), 1.76–1.02 (m, 22 H), 0.91 (t, J = 7.8 Hz, 3 H), 0.82
(d, J = 7.8 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 173.9,
171.7, 157.4, 130.3, 128.8, 114.5, 73.2, 69.1, 66.6, 61.3,
56.0, 49.4, 42.1, 39.0, 33.9, 33.2, 29.7, 24.1, 20.7, 19.0, 14.0.
IR (KBr): nmax = 3429, 2924, 2856, 1728, 1632, 1511, 1459,
1247 cm–1. ESI-HRMS: m/z [M + Na]+ calcd for
130.2, 129.9, 114.8, 114.5, 75.4, 72.2, 69.0, 61.45, 55.7,
55.5, 39.0, 38.7, 37.3, 33.5, 33.3, 31.5, 30.1, 29.6, 25.1, 24.1,
20.5, 17.9, 14.2. IR (film): n = 3437 (OH), 2926, 2869, 1728,
1636, 1512, 1247, 1038 cm–1. ESI-MS: m/z = 544 [M + Na]+.
(3S,10R,13S)-3-[4-(2-hydroxyethoxy)benzyl]-13-[(S)-2-
hydroxy pentyl]-4,10-dimethyl-1-oxa-4-
azacyclotridecane-2,5-dione [PF1163 A(1)]
To a stirred solution of 21 (0.02 g, 0.03 mmol) in anhyd
TFA–CH2Cl2 (1:5, 2 mL) was added at 0 °C, and the reaction
mixture was stirred for 2 h at r.t. The reaction mixture was
quenched with NaHCO3 (1 mL) and extracted with CH2Cl2
(2 × 2 mL), and the combined organic layers were washed
with brine (2 mL), dried (Na2SO4), and concentrated under
C27H43O6NNa: 500.2988; found: 500.2979.
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