Stereoselective total synthesis of (+)-anamarine via cross-metathesis protocol

Article abstract of DOI:10.1016/j.tetlet.2010.08.077

A convergent stereoselective total synthesis of (+)-anamarine via cross-metathesis (CM) protocol starting from 2-butyn-1,4-diol and vinyl lactone is reported. Other key features of the strategy include the use of Sharpless asymmetric epoxidation, Sharples

Full text of DOI:10.1016/j.tetlet.2010.08.077

Tetrahedron Letters 51 (2010) 5736–5739
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Tetrahedron Letters
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Stereoselective total synthesis of (+)-anamarine via cross-metathesis protocol
⇑
Gowravaram Sabitha , C. Nagendra Reddy, Peddabuddi Gopal, J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A convergent stereoselective total synthesis of (+)-anamarine via cross-metathesis (CM) protocol starting
from 2-butyn-1,4-diol and vinyl lactone is reported. Other key features of the strategy include the use of
Sharpless asymmetric epoxidation, Sharpless dihydroxylation, and Red-Al reduction.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 28 July 2010
Revised 23 August 2010
Accepted 25 August 2010
Available online 31 August 2010
Keywords:
d-Lactone
Sharpless epoxidation
Sharpless dihydroxylation
Red-Al
Cross-metathesis
Anamarine (1)1 is a member of the polyoxygenated 5,6-dihy-
dro-2H-pyran-2-one ( ,b-unsaturated d-lactone)-containing natu-
ral product family isolated from the flowers and leaves of a
Accordingly, the synthesis of 1 starts with the readily available
2-butyn-1,4-diol 8 (Scheme 2) that was subjected to selective
monobenzylation to afford the propargyl alcohol 9. Partial reduc-
tion of the triple bond using LAH gave low yields of product along
with an unknown by-product. However, using Red-Al in THF, the
problem was solved and the required allylic alcohol 10 was
obtained in a very good yield (90%). The alcohol 10 was subjected
to Sharpless asymmetric epoxidation [(+)-DIPT/Ti(OiPr)4/TBHP/
ꢀ20 °C, 24 h, 92%] to afford epoxy alcohol 11, which was converted
into propargylic alcohol 13 by a two-step process; first by convert-
ing to chloro epoxy compound 12 which on elimination using
a
Peruvian Hyptis. Other members of the
a,b-unsaturated d-lactone
family are spicigerolide (2),2 hyptolide (3),3 synrotolide diacetate
(4),4 and synargentolide (5)5 (Fig. 1) isolated from the Hyptis and
Syncolostemon and related genera of the family Lamiaceae. These
compounds have been found to exhibit antibacterial, antifungal,
as well as cytotoxicity against human tumor cells.6 In addition,
6-substituted-a,b-unsaturated-d-lactones have been reported to
inhibit HIV protease,7 induce apoptosis,8,9 and have proven to be
anti-leukemic,10 along with having many other relevant pharma-
cological properties.11 Thus, these lactones have attracted the
attention of synthetic chemists. Recently we have reported the first
synthesis of synargentolide.12 In continuation of our efforts toward
the synthesis of naturally occurring six-membered lactones,13 we
became interested in the synthesis of the natural lactone anama-
rine by a convergent strategy using a cross-metathesis (CM) proto-
col. So far three syntheses14 have been reported for 1. Herein, we
report the stereoselective total synthesis of (+)-anamarine 1 from
the readily available starting materials 2-butyn-1,4-diol and 3-bu-
tyn-1-ol.
OAc OAc
OAc OAc
O
O
O
O
O
O
OAc OAc
anamarine 1
OAc OAc
spicigerolide 2
OAc OAc
OH
OAc
O
O
OAc
OAc OH
synrotolide 4
Retrosynthetic analysis reveals that the target compound 1
(Scheme 1) can be obtained by CM reaction of olefin 6 and vinyl
lactone 7. The substrate 6 in turn could be made from the commer-
cially available 2-butyn-1,4-diol by sequential reactions, whereas,
the vinyl lactone 713o is accessible from 3-butyn-1-ol.
hyptolide 3
OAc
O
O
OAc OAc
synargentolide 5
⇑
Corresponding author. Tel.: +91 40 27191629; fax: +91 40 27160512.
E-mail address: gowravaramsr@yahoo.com (G. Sabitha).
Figure 1. Polyoxygenated 5,6-dihydro-2H-pyran-2-one
tone)-containing natural products.
(a,b-unsaturated d-lac-
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.077

G. Sabitha et al. / Tetrahedron Letters 51 (2010) 5736–5739
5737
O
MOM
OH
OAc OAc
O
O
O
O
+
O
OMOM
OAc OAc
MOM
HO
7
6
anamarine 1
OH
OH
3-butyn-1-ol
8
Scheme 1. Retrosynthesis.
O
e, f
OBn
c, d
b
HO
OBn
R
OR
HO
8: R = H
9: R = Bn
11: R = OH
12: R = Cl
10
a
HO
g
OBn
OMOM
h
i, j
HO
OBn
OBn
OMOM
15
OR
13: R = H
14: R = MOM
16
OR
OR OMOM
O
k, l
o, p
m, n
OBn
OMOM
R
OBn
OMOM
OBn
OH OMOM
19: R = H
20: R = MOM
17: R = OH
18: R = I
21: R = H
22: R = Ts
OMOM
OR
OR OH
s
q, r
t, u
R'
OR OR
25: R = MOM
OBn
OR OMOM
OR OR
6: R = MOM
23: R = H
24: R = MOM
26: R' = CH2OH
27: R' = CHO
O
OR OR
O
O
v
O
+
OR OR
2
28: R = H
29: R = Ac
No desired product
only vinyl lactone self dimer
is formed
7
Scheme 2. Reagents and conditions: (a) NaH, BnBr, anhydrous THF, 0 °C–rt, 24 h, 53%; (b) Red-Al, anhydrous THF, rt, 1 h, 90%; (c) Ti(OiPr)4, (+)-DIPT, TBHP, anhydrous CH2Cl2,
ꢀ20 °C, 24 h, 92%; (d) PPh3, NaHCO3, anhydrous CCl4, reflux, 3 h, 84%; (e) nBuLi, anhydrous THF, ꢀ78 °C, 3 h, 81%; (f) MOMCl, DIPEA, anhydrous CH2Cl2, 0 °C–rt, 2 h, 91%; (g)
EtMgBr, (CH2O)n, anhydrous THF, rt, 5 h, 75%; (h) Red-Al, anhydrous THF, rt, 1 h, 94%; (i) Ti(OiPr)4, (ꢀ)-DIPT, TBHP, anhydrous CH2Cl2, ꢀ20 °C, 24 h, 94%; dr (49:1) (j) PPh3,
imidazole, I2, Et2O/AcN, (3:1) 0 °C–rt, 0.5 h, 92%; (k) Zn dust, EtOH, reflux, 1 h, 90%; (l) MOMCl, DIPEA, anhydrous CH2Cl2, 0 °C–rt, 2 h, 92%; (m) AD-mix-b, tBuOH/H2O (1:1),
0 °C, 6 days, 90%; dr (9:1); (n) TsCl, TEA, nBu2SnO, anhydrous CH2Cl2, 0 °C–rt, 1 h, 91%; (o) LAH, anhydrous THF, reflux, 1 h, 82%; (p) MOMCl, DIPEA, anhydrous CH2Cl2, 0 °C–rt,
2 h, 93%; (q) Pd/C, H2, EtOAc, rt, 16 h, 95%; (r) (COCl)2, DMSO, TEA, anhydrous CH2Cl2, ꢀ78 °C, 2 h, 92%; (s) vinylmagnesium bromide, MgBr2–Et2O, anhydrous CH2Cl2, ꢀ78 °C,
1 h, 74%; de (>95%); (t) 3 N HCl MeoH/AcN (1:1), 0 °C–rt, 8 h, 80%; (u) Ac2O, TEA, DMAP, CH2Cl2, 0 °C–rt,0.5 h, 91%; (v) Grubb’s-II, dry CH2Cl2, reflux, 5 h (90%).
n-BuLi afforded the propargylic alcohol 13 (83% yield over two
steps). The hydroxyl group in 13 was protected as its MOM ether
(MOMCl/DIPEA/CH2Cl2/0 °C to rt, 2 h, 91%) to afford 14. The
MOM ether 14 was treated with Grignard reagent prepared from
ethyl bromide and magnesium followed by quenching with para
formaldehyde in dry THF to afford 15 in 75% yield. In order to
get the trans-allyl alcohol, compound 15 was treated with Red-Al
in THF at rt, which reduced the alkyne to the desired trans-olefin
16 in 94% yield. In the next step, olefin 16 was subjected to Sharp-
less asymmetric epoxidation using (ꢀ)-DIPT, Ti(OiPr)4, and TBHP to
furnish the desired epoxy alcohol 17, which was converted into the
corresponding epoxy iodide 18 in 92% yield. Compound 18 on

5738
G. Sabitha et al. / Tetrahedron Letters 51 (2010) 5736–5739
OR OR
OR OH
O
O
a
O
O
b, c
6
7
+
OR OR
OR OR
30: R = MOM
Exclusive product
31: R = H
1: R = Ac
Grubbs'II
Scheme 3. Reagents and conditions: (a) anhydrous CH2Cl2, reflux, 0.5 h, 86%; (b) 3 N HCl, MeOH/AcCN (1:1), 0 °C–rt, 8 h, 80%; (c) Ac2O, TEA, DMAP, anhydrous CH2Cl2, 0 °C–rt,
0.5 h, 91%.
Villavicencio, M. J.; Novelo, M.; Ibarra, P.; Chai, H.; Pezzuto, J. M. J. Nat. Prod.
1993, 56, 583–593.
7. (a) Romines, K. R.; Chrusciel, R. A. Curr. Med. Chem. 1995, 2, 825–838; (b)
refluxing in ethanol in the presence of Zn dust eliminated to afford
allylic alcohol 19 and the resulting alcohol was protected as MOM
ether 20. Asymmetric dihydroxylation15 of 20 using AD-mix-b in
Aristoff, P. A. Drugs Future 1998, 23, 995–999; (c) Hagen, S. E.; Vara-Prasad, J. V.
N.; Tait, B. D. Adv. Med. Chem. 2000, 5, 159–195; (d) Hagen, S. E.; Domagala, J.
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Urumov, A.; Zeikus, G.; Zeikus, E.; Lunney, E. A.; Pavlovsky, A.; Gracheck, S. J.;
tBuOH/H2O (1:1) at 0 °C gave the diol 21 in 90% yield (dr 9:1).
Selective conversion of the primary hydroxyl group of 21 into a
tosylate was carried out using tosyl chloride in the presence of
TEA and nBu2SnO in CH2Cl2 to give 22 in 91% yield, which was re-
duced to the methyl compound by using LiAlH4 in THF in 82% yield.
The secondary alcohol was protected as its MOM ether 25 and the
benzyl group was removed using Pd/C, H2 in EtOAc to afford the
primary alcohol 26, which was converted into the corresponding
aldehyde 27 under Swern oxidation conditions. To create a fourth
stereogenic center with the required stereochemistry, a chelation-
controlled vinyl Grignard reaction16 was performed. Thus, adding a
solution of vinylmagnesium bromide in THF to the complex
formed between 27 and 1 equiv of magnesium bromide etherate
in CH2Cl2, provided the chelation-controlled product 6 in excellent
yield and with high (>95%) diastereofacial selectivity.
The three MOM groups were removed and subsequently pro-
tected as acetates to give tetraacetate derivative 29, which was ex-
pected to give directly the target molecule 1 when subjected to
cross-metathesis reaction with vinyl lactone 7 using Grubb’s II gen-
eration catalyst. But, this reaction failed to give the desired target 1,
instead it gave exclusively the dimer of vinyl lactone (Scheme 2).
However, the tri MOM derivative 6 underwent CM reaction
smoothly with vinyl lactone 7 using Grubb’s II generation catalyst
to yield the desired lactone 30 (86%) exclusively (Scheme 3).
Subsequent removal of MOM groups in 30 using 3 N HCl in
MeOH/CH3CN (1:1), at 0 °C afforded tetrahydroxy derivative 31
(80%). Acetylation of 31 with acetic anhydride in the presence of
TEA and DMAP furnished the target lactone, anamarine 117 in
91% yield. The spectral data of the synthetic compound matched
with the literature values.14c
Saunders, J. M.; VanderRoest, S.; Brodfuehrer, J. J. Med. Chem. 2001, 44, 2319–
2332; (e) Agrawal, V. K.; Singh, J.; Mishra, K. C.; Khadikar, P. V.; Jaliwala, Y. A.
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Huang, Z. W. Chem. Biol. 2002, 9, 1059–1072.
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Commun. 2001, 287, 829–832; (c) Raoelison, G. E.; Terreaux, C.; Queiroz, E. F.;
Zsila, F.; Simonyi, M.; Antus, S.; Randriantsoa, A.; Hostettmann, K. Helv. Chim.
Acta 2001, 84, 3470–3476; (d) Lewy, D. S.; Gauss, C.-M.; Soenen, D. R.; Boger, D.
L. Curr. Med. Chem. 2002, 9, 2005–2032; (e) Larsen, A. K.; Escargueil, A. E.;
Skladanowski, A. Pharmacol. Ther. 2003, 99, 167–181; (f) Richetti, A.; Cavallaro,
A.; Ainis, T.; Fimiani, V. Immunopharmacol. Immunotoxicol. 2003, 25, 441–449;
(g) Koizumi, F.; Ishiguro, H.; Ando, K.; Kondo, H.; Yoshida, M.; Matsuda, Y.;
Nakanishi, S. J. Antibiot. 2003, 56, 603–609.
12. Sabitha, G.; Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron Lett. 2009, 46, 6298–
6302.
13. (a) Sabitha, G.; Sudhakar, K.; Reddy, N. M.; Rajkumar, M.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6567–6570; (b) Sabitha, G.; Narjis, F.; Swapna, R.;
Yadav, J. S. Synthesis 2006, 17, 2879–2884; (c) Sabitha, G.; Reddy, E. V.;
Yadagiri, K.; Yadav, J. S. Synthesis 2006, 19, 3270–3274; (d) Sabitha, G.;
Sudhakar, K.; Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599–8602; (e) Sabitha, G.;
Bhaskar, V.; Yadav, J. S. Tetrahedron Lett. 2006, 47, 8179–8181; (f) Sabitha, G.;
Swapna, R.; Reddy, E. V.; Yadav, J. S. Synthesis 2006, 24, 4242–4246; (g) Sabitha,
G.; Bhikshapathi, M.; Yadav, J. S. Synth. Commun. 2007, 37(4), 561–569; (h)
Sabitha, G.; Gopal, P.; Yadav, J. S. Synth. Commun. 2007, 37, 1495–1502; (i)
Sabitha, G.; Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 1651–1652; (j)
Sabitha, G.; Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 8065–8068; (k)
Sabitha, G.; Bhaskar, V.; Yadav, J. S. Synth. Commun. 2008, 38, 1–12; (l) Sabitha,
G.; Bhaskar, V.; Siva Sankara Reddy, S.; Yadav, J. S. Tetrahedron 2008, 64(44),
10207–10213; (m) Sabitha, G.; Bhaskar, V.; Siva Sankara Reddy, S.; Yadav, J. S.
Synthesis 2009, 3285; (n) Sabitha, G.; Gopal, P.; Reddy, C. N.; Yadav, J. S.
Synthesis 2009, 3301; (o) Sabitha, G.; Fatima, N.; Gopal, P.; Reddy, C. N.; Yadav,
J. S. Tetrahedron: Asymmetry 2009, 20, 184–191; (p) Sabitha, G.; Fatima, N.;
Reddy, E. V.; Yadav, J. S. Tetrahedron Lett. 2008, 49(42), 6087–6089; (q)
Synthesis of Obolactone, Sabitha, G.; Prasad, M. N.; Shankaraiah, K. S.; Jadav, J.
S. Synthesis 2010, 1171–1175; (r) Sabitha, G.; Reddy, N. M.; Prasad, M. N.;
Yadav, J. S. Helv. Chim. Acta 2009, 92, 967; (s) Sabitha, G.; Bhaskar, V.; Siva
Sankara Reddy, S.; Yadav, J. S. Helv. Chim. Acta 2010, 93, 329–338.
14. (a) Lorenz, K.; Frieder, L. W. Tetrahedron Lett. 1987, 28, 6437–6440; (b) Diaz-
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6925.
In summary, we accomplished the stereoselective total synthe-
sis of (+)-anamarine via the CM protocol.
Acknowledgments
C.N.R. thanks UGC, and P.G. thanks CSIR, New Delhi for the
award of fellowships.
References and notes
1. Alemany, A.; Márquez, C.; Pascual, C.; Valverde, S.; Martínez-Ripoll, M.; Fayos,
J.; Perales, A. Tetrahedron Lett. 1979, 20, 3583–3586.
2. Pereda-Miranda, R.; Fragoso-Serrano, M.; Cerda-García-Rojas, C. M. Tetrahedron
2001, 57, 47–53.
3. Achmad, S. A.; Høyer, T.; Kjær, A.; Makmur, L.; Norrestam, R. Acta Chem. Scand.
1987, 41B, 599–609.
4. Coleman, M. T. D.; English, R. B.; Rivett, D. E. A. Phytochemistry 1987, 26, 1497–
1499.
5. Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A. Phytochemistry 1998, 48,
651–656.
6. (a) Pereda-Miranda, R.; Fragoso-Serrano, M.; Cerda-Garcia-Rojas, C. M.
Tetrahedron 2001, 57, 47–53; (b) Pereda-Miranda, R.; Hernandez, L.;
16. (a) Venkatesan, K.; Srinivasan, K. V. Tetrahedron: Asymmetry 2008, 19, 209–215;
(b) Keck, G. E.; Andrus, M. B.; Romer, D. R. J. Org. Chem. 1991, 56, 417–420.
17. Analytical data of all the new compounds are given below. (R)-5-(Benzyloxy)-4-
(methoxymethoxy)pent-2-yn-1-ol (15): ½a D25
¼ ꢀ79:6 (c 1, CHCl3); IR (KBr) 3426,
ꢁ
3030, 2929, 1452, 1027 cmꢀ1 1H NMR (300 MHz, CDCl3): d 7.34–7.27 (m, 5H,
;
ArH), 4.88 (d, J = 6.0 Hz, 1H,), 4.61 (d, J = 6.7 Hz, 1H), 4.59 (m, 1H), 4.53 (ABq,

G. Sabitha et al. / Tetrahedron Letters 51 (2010) 5736–5739
5739
J = 12.5, 18.2 Hz, 2H, CH2–OAr), 4.22 (d, J = 1.5 Hz, 2H), 3.62 (d, J = 5.2 Hz, 2H),
3.37 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): d 137.6, 128.3, 127.5, 127.4, 94.1,
85.0, 81.1, 73.3, 72.1, 65.1, 55.5, 50.5; HRMS calcd for C14H18O4Na: 273.1102;
found: 273.1112.
CH3), 3.35 (s, 3H, CH3), 3.33 (s, 3H, CH3), 1.21 (d, J = 6.7 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d 138.0, 128.3, 127.7, 127.6, 97.7, 97.2, 95.1, 79.6, 76.5, 73.3,
73.2, 70.2, 56.0, 55.7, 55.3, 16.3; HRMS calcd for C18H30O7Na: 381.1889; found:
381.1900.
((2R,3S)-3-((S)-2-(Benzyloxy)-1-(methoxymethoxy)ethyl)oxiran-2-yl)methanol
(3R,4S,5S,6S)-4,5,6-Tris(methoxymethoxy)hept-1-en-3-ol (6): ½a D25
¼ ꢀ16:1 (c 1,
ꢁ
(17): ½a 2D5
ꢁ
¼ þ1:0 (c 1, CHCl3); IR (KBr) 3444, 2897, 1453, 1101, 1031 cmꢀ1
;
1H
CHCl3); IR (KBr) 3451, 2932, 1150, 1029, 918 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
NMR (300 MHz, CDCl3): d 7.36–7.20 (m, 5H, ArH), 4.77 (d, J = 6.6 Hz, 1H, CH),
4.67 (d, J = 6.4 Hz, 1H, CH), 4.53 (ABq, J = 12.0, 14.0 Hz, 2H, CH2–OAr), 3.84 (d,
J = 12.4 Hz, 1H), 3.65–3.51 (m, 4H), 3.36 (s, 3H, CH3); 3.10 (d, J = 2.2 Hz, 1H)
3.02 (d, J = 1.32 Hz, 1H), 1.70 (brds, 1H, OH); 13C NMR (75 MHz, CDCl3): d 137.7,
128.3, 127.6, 127.4, 95.7, 75.6, 73.3, 70.0, 61.1, 56.1, 55.5, 55.4; HRMS calcd for
d 5.97 (m,1H), 5.40 (td, J = 1.5,10.5 Hz,1H), 5.21 (td, J = 1.5, 11 Hz,1H), 4.81–
4.64 (m, 6H), 4.34–4.25 (m, 1H), 3.90 (m,1H), 3.74 (m, 1H), 3.63 (ABq, J = 4.7,
9.6 Hz,1H), 3.44 (s, 3H, CH3), 3.43 (s, 3H, CH3), 3.38 (s, 3H, CH3), 1.27 (d,
J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3): d 137.4, 116.8, 98.5, 97.6, 95.2,
82.5, 79.8, 72.7, 71.8, 56.1, 56.0, 55.4, 16.4; HRMS calcd for C13H26O7Na:
317.1576; found: 317.1578.
C
14H20O5Na: 291.1208; found: 291.1214.
1-(((2S,3S)-2,3-Bis(methoxymethoxy)pent-4-enyloxy)methyl)benzene (20):
½
a 2D5
ꢁ
(R)-5,6-Dihydro-6-((E,3R,4S,5S,6S)-3-hydroxy-4,5,6-tris(methoxymethoxy)hept-
¼ þ18:8 (c 1, CHCl3); IR (KBr) 2891, 1452, 1151,1033, 919 cmꢀ1
;
1H NMR
1-enyl)pyran-2-one (30): ½a D25
¼ þ5:2 (c 1, CHCl3); IR (KBr) 3444, 2930, 1722,
ꢁ
(300 MHz, CDCl3):
d
7.34–7.25 (m, 5H, ArH), 5.78 (m, 1H), 5.31 (dd,
1246, 1029, 916 cmꢀ1 1H NMR (300 MHz, CDCl3): d 6.89 (m,1H), 6.10–5.93 (m,
;
J = 2.2,17.3 Hz, 1H), 5.24 (dd, J = 3.0, 10.5 Hz,1H), 4.83–4.61 (m, 4H), 4.54
(ABq, J = 12.0, 15.1 Hz, 2H, CH2–OAr); 4.23 (m, 1H), 3.78 (m, 1H), 3.67–3.48 (m,
3H), 4.98 (m, 1H), 4.82–4.63 (m, 6H), 4.22 (m, 1H), 3.88 (dt, J = 5.5, 24.2 Hz,
1H), 3.71 (dt, J = 3.7, 30.7 Hz, 1H), 3.64 (m, 1H), 3.43 (s, 3H, CH3), 3.42 (s, 3H,
CH3), 3.37 (s, 3H, CH3), 2.48 (m, 2H), 1.28 (d, J = 6.5 Hz, 3H,CH3); 13C NMR
(75 MHz, CDCl3): d 163.8, 144.4, 132.6, 128.7, 121.6, 98.3, 97.7, 95.2, 82.3, 79.7,
76.3, 73.5, 72.7, 56.1, 55.9, 55.4, 29.4, 16.4; HRMS calcd for C18H30O9Na:
413.1787; found: 413.1808.
2H), 3.36 (s, 3H, CH3), 3.33 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3):
d
137.6,134.2, 127.8 127.1, 127.0, 118.1, 96.5, 93.7, 77.7, 76.3,72.9, 69.6, 55.2,
55.1; HRMS calcd for C16H24O5Na: 319.1521; found: 319.1517.
(2S,3S,4S)-5-(Benzyloxy)-3,4-bis(methoxymethoxy)pentane-1,2-diol (21):
½ ꢁ
a 2D5
¼ ꢀ11:0 (c 1, CHCl3); IR (KBr) 3380, 2933, 1452, 1153, 1026 cmꢀ1
;
1H NMR
Anamarine (1): white solid: mp = 109–111 °C; ½a D25
¼ þ17:8 (c 0.3, CHCl3); IR
ꢁ
(300 MHz, CDCl3): d 7.37–7.21 (m, 5H, ArH), 4.79–4.60 (m, 4H), 4.53 (q, J = 12.2,
13.4 Hz, 2H, CH2–OAr), 4.03 (t, J = 5.4 Hz, 1H), 3.79–3.58 (m, 6H), 3.39 (s, 3H,
CH3); 3.38 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): d 137.6, 128.3, 127.7, 127.6,
98.4, 97.4, 78.6, 76.4, 73.4, 70.7, 69.4, 63.1, 56.3, 55.9; HRMS calcd for
(KBr) 2925, 1739, 1374, 1023, 974 cmꢀ1 1H NMR (300 MHz, CDCl3): d 6.88
;
(ddd, J = 3.5, 5.2, 9.9 Hz, 1H), 6.05 (ddd, J = 1.7, 1.7, 9.9 Hz, 1H), 5.88–5.74 (m,
2H), 5.36 (dd, J = 5.2, 7.2 Hz, 1H), 5.30 (dd, J = 3.5, 7.2 Hz, 1H), 5.17 (dd, J = 3.5,
7.0 Hz,1H), 4.96 (m, 1H) 4.90 (dq, J = 6.4, 6.4 Hz, 1H), 2.45 (m, 2H), 2.11 (s, 3H,
CH3), 2.07 (s, 3H, CH3), 2.06 (s, 3H, CH3), 2.03 (s, 3H, CH3), 1.17 (d, J = 6.4 Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3): d 170.0, 169.8, 169.7, 169.5, 163.4, 144.5,
133.0, 125.6, 121.5, 75.9, 71.9, 71.5, 70.4, 67.5, 29.4, 21.0, 20.9, 20.8, 20.7, 15.9;
HRMS calcd for C20H26O10Na: 449.1423; found: 449.1434.
C
16H26O7Na:353.1576; found: 353.1564.
1-(((2S,3S,4S)-2,3,4-Tris(methoxymethoxy)pentyloxy)methyl)benzene (24): ½ ꢁ
a 2D5
¼ þ1:5 (c 1, CHCl3); IR (KBr) 2934, 2891, 1452,1150, 917 cmꢀ1
;
1H NMR
(300 MHz, CDCl3): d 7.32–7.27 (m, 5H, ArH), 4.74–4.57 (m, 6H), 4.52 (q, J = 12.0,
14.3 Hz, 2H, CH2–OAr), 3.90–3.74 (m, 3H), 3.63–3.51 (m, 2H, CH2), 3.37 (s, 3H,