Total synthesis of mniopetals A, B, C and D

Article abstract of DOI:10.1055/s-0033-1339172

A total synthesis of the mniopetals A, B, C and D is described. Key steps are a Sharpless asymmetric dihydroxylation and a selective esterification of an equatorial hydroxy group vicinal to an axial hydroxy function. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0033-1339172

1410▌
LETTER
letter
Total Synthesis of Mniopetals A, B, C and D
Total Synthesis of Mniopetals A, B, C and D
Joachim Weihrather, Johann Jauch*
Institut für Organische Chemie II, Universität des Saarlandes, 66123 Saarbrücken, Germany
Fax +49(681)30264151; E-mail: j.jauch@mx.uni-saarland.de
Received: 27.03.2013; Accepted after revision: 07.05.2013
Dedicated to Prof. Dr. W. Steglich on the occasion of his 80th birthday
strategy for the construction of these acids in enantiomer-
ically pure form (Figure 1) and suitable methods for ester-
ification with mniopetal E. Here, we wish to report our
efforts in this direction.
Abstract: A total synthesis of the mniopetals A, B, C and D is de-
scribed. Key steps are a Sharpless asymmetric dihydroxylation and
a selective esterification of an equatorial hydroxy group vicinal to
an axial hydroxy function.
Key words: asymmetric synthesis, antiviral agents, chemoselectiv- (R)-2-Acetoxydecanoic acid (9), MEM-protected (R)-2-
ity, intramolecular Diels–Alder reaction, natural products
hydroxydecanoic acid (10) and MEM-protected (R)-2-hy-
droxyoctanoic acid (11) were synthesized starting with a
Sharpless asymmetric dihydroxylation with AD-MIX-β
of the corresponding terminal olefin (Scheme 1).3
In 1994, Anke and Steglich reported on the isolation,
structure elucidation and determination of the absolute
configuration of six new drimane-type sesquiterpenes
from the culture broth of the Canadian fungus Mniopeta-
lum sp. 87256, the mniopetals A–F (1a–f; Figure 1).1
R1
2 R1 = n-C8H17
3 R1 = n-C6H13
AD-mix-β
t-BuOH–H2O
99%
OH
O
O 11
15
R1
12
H
R2
98% ee
1
4
9
10
O
2
8
5
1. TBDPSCl
DMF, 89%
3
7
OH
R
OMEM
6
R
H
OH
OH
R1
2. MEMCl
CH2Cl2, 91%
3. TBAF
R1
14 13
1
4 R1 = n-C8H17
5 R1 = n-C6H13
7 R1 = n-C8H17
8 R1 = n-C8H13
R1
OH
OH
OH
R2
AcO
THF, 94%
H
10´
1a
1b
1c
1d
1e
1f
1. i) TBDMSCl, Py
ii) Ac2O, 60%
2. HCl
THF, 80%
1. Dess–Martin
CH2Cl2, 88%
2. NaClO2
1´
9´
7´
7´
7´
5´
3´
COO–
8´
6´
4´
4´
4´
2´
2´
2´
HO
H
1´
COO–
H
1´
COO–
10´
t-BuOH, 87%
9´
5´
5´
3´
8´
8´
6´
6´
HO
O
OR2
3´
12´
R
11´
O
O
RuCl3
R1
HO
H
R
OH
OH
OH
H
NaIO4
82%
R1
OH
COO–
6 R1 = n-C8H17
9 R1 = n-C8H17 R2 = Ac
10 R1 = n-C8H17 R2 = MEM
11 R1 = n-C6H13 R2 = MEM
OH
OH
Scheme 1 Common synthetic strategy for the carboxylic acid side
chains 9, 10 and 11
Figure 1 Structures of mniopetals A–F (1a–f)
In order to acetylate the secondary hydroxyl function in 4,
the primary one had to be protected temporarily. This
could be accomplished in a one-pot procedure by si-
lylation with TBDMSCl–pyridine, acetylation with Ac2O
and finally removal of the TBDMS group with dilute HCl
to give 6 in good yield.3a Oxidation of 6 with RuCl3–
The mniopetals inhibit the reverse transcriptase of HIV-1,
which makes them attractive targets for total synthesis.2
Some years ago, we developed short syntheses of mni-
opetals E and F.2b–d,2g Esterification of the two secondary
alcohol functions with the respective α-hydroxy or α-ace-
toxy carboxylic acids should lead directly to the mni-
opetals A–D. Therefore, it was necessary to find a simple
3a
NaIO4 yielded 9 (side chain for 1a). For the other side
chains, the primary hydroxy group of 4 and 5 was silylat-
ed, then the secondary hydroxy group was protected as
MEM acetal4 and the silyl protecting group was removed
under standard conditions to give 7 and 8. Oxidation of
the primary hydroxy group to the carboxylic acid in two
SYNLETT 2013, 24, 1410–1414
Advanced online publication: 10.06.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339172; Art ID: ST-2013-B0271-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Total Synthesis of Mniopetals A, B, C and D
1411
steps4 gave 10 and 11, respectively. The ee and the abso-
lute configuration of hydroxyacids 10 and 11 were deter-
mined according to Mosher’s method.5 The enantiomeric
excess of the synthesized acids exceeds 98%.
OTHP
OTHP
O
O
OR2
O
O
H
HO
HO
H
HO
O
9, 10 or 11
R1
1
1
O
O
2
2
DCC, DMAP
CH2Cl2
81–85%
O
H
H
With the side chain acids for the mniopetals A–D in hand,
esterification of 9 with the mniopetal E precursor 122d was
straightforward, but the final cleavage of the menthyl ac-
etal under standard conditions led to complete decompo-
sition of the product (Scheme 2). Thus, we exchanged the
menthyl group with a THP protecting group,6,7 starting
from 132d according to Scheme 2. Compound 15 was fi-
nally cis-dihydroxylated chemo- and stereoselectively2,8
to yield 16.
17 R1 = n-C8H17 R2 = Ac
18 R1 = n-C8H17 R2 = MEM
19 R1 = n-C6H13 R2 = MEM
16
1b
40%
R2 = Ac
PPTS
R
2 = MEM
ZnBr2
acetone–H2O CH2Cl2
65%
1a
1c
45%
Scheme 3 Syntheses of mniopetals A, B and C (1a, 1b and 1c)
O(+)Menthyl
O
O
HO
HO
H
1. 9, DCC, DMAP
2. TFA–H2O–acetone
OTHP
H
OTHP
O
O
O
O
O
decomposition
H
HO
HO
HO
TBDMSO
TBDMSOTf
2,6-lutidine
1
1
O
O
2
2
H
CH2Cl2, –78 °C
82%
12
H
H
OH
H
O-(+)-menthyl
O
O
16
20
O
O
H
11´
12´
acetone
TFA–H2O
O
14´
O
O
H17C8
O
O
O
13´
1. Py-HF
THF, 79%
2. ZnBr2
CH2Cl2, 55%
quant.
OTHP
O
O
10, 2,4,6-trichloro-
benzoyl chloride
DMAP, toluene
H
H
O
H
TBDMSO
14
13
1
O
2´
3´
2
1d
1´
OTHP
H
O
72%
O
O
O
O
4´
H
5´
H
O
HO
HO
OsO4
1
21
O
O
O
2
THF–H2O
68%
PPTS
CH2Cl2
81%
Scheme 4 Synthesis of mniopetal D
H
H
15
16
After silylation of the hydroxy group at C2, 13 leading to
20, Steglich esterification of the hydroxy group at C1 was
not possible, probably due to a shielding effect of the huge
silyl group and the innately lower reactivity of an axial hy-
droxy function. After extensive experimentation, we
found that the Yamaguchi esterification with 2,4,6-tri-
chlorobenzoyl chloride, hydroxyacid 10, triethylamine
Scheme 2 Cleavage of the menthyl acetal after esterification of 12
with 9 was not possible. Therefore the menthyl group in 11 had to be
exchanged with a THP group to give 16.
Mniopetal E precursor 16 contains equatorial and axial
hydroxy groups at C2 and C1, respectively. Esterification
of the equatorial hydroxy group is possible without pro-
tection of the axial hydroxy group (Scheme 3).9 For the
carboxylic acids 9, 10 and 11 the Steglich esterification
with DCC–DMAP10 in dichloromethane is the method of
choice (Scheme 3).
and DMAP14 gives 21 in 72% yield. The following desi-
15,16
lylation has to be done with Py·HF complex,
since
with TBAF migration of the acyl group to the equatorial
hydroxyl group occurs. Finally, the acetal protecting
groups MEM and THP were both cleaved with ZnBr2–
CH2Cl2 leading to mniopetal D (1d) in 55% yield (average
74% per protecting group).
The THP group in 17 was cleaved with PPTS in acetone–
water11 to obtain mniopetal A (1a) in 65% yield. Mni-
opetals B and C (1b, 1c) were obtained in 40% and 45%
yield from 18 and 19, respectively, after deprotection of
the THP and MEM acetals in one step with ZnBr2–CH2Cl2
(average yield for cleavage of each protecting group was
63–65%).
All synthesized mniopetals were identical in all respects
with the isolated products.
In summary, we have developed short and efficient syn-
theses of all known mniopetals.17 Key features of our
strategy are a straightforward construction of the side
chain carboxylic acids and fine-tuned methods to manip-
ulate an equatorial hydroxy group vicinal to an axial
hydroxy group and vice versa.
For the synthesis of mniopetal D (1d) the equatorial hy-
droxy group of diol 16 had to be protected selectively,
which was achieved with TBDMSOTf–2,6-lutidine in di-
chloromethane at –78 °C (Scheme 4).12
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1410–1414

1412
J. Weihrather, J. Jauch
LETTER
129.5 (C-2), 126.2 (C-1), 99.2 (C-11), 94.7 (C-1′), 61.4 (C-
5′), 49.9 (C-9), 48.2 (C-10), 44.9 (C-5), 41.2 (C-3), 31.14 (C-
13), 31.05 (C-4), 29.8 (C-2′), 25.2 (C-4′), 24.6 (C-6), 24.2
(C-14), 18.1 (C-3′). [α]20D –22.2 (CHCl3, c = 0.1). HRMS
(ESI+): m/z [M + Na]+ calcd for C20H26O5Na: 369.1678;
found: 369.1634.
Acknowledgment
We are grateful to Alfred Weihrather from the Analytical Service
Centre of Huntsman Textile Effects at Langweid (Lech), Germany,
for the HRMS measurements and to Prof. Dr. W. Steglich for copies
of the NMR spectra of the isolated natural products. Financial sup-
port from the Universität des Saarlandes is greatly acknowledged.
(8) (a) Altenbach, H.-J.; Voss, B.; Vogel, E. Angew. Chem. Int.
Ed. 1983, 22, 410; Angew. Chem. 1983, 95, 424. (b) Van
Rheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett.
1976, 1973.
References and Notes
(9) Fattorusso, E.; Romano, A.; Bavestrello, G.; Bonelli, P.;
Calcinai, B. Tetrahedron Lett. 2006, 47, 2197.
(1) (a) Kuschel, A.; Anke, T.; Velten, R.; Klostermeyer, D.;
Steglich, W.; König, B. J. Antibiot. 1994, 47, 733.
(10) (a) Bhat, S. V.; Bajwa, B. S.; Dornauer, H.; de Souza, N. J.
J. Chem. Soc., Perkin Trans. 1 1982, 767. (b) Steglich, W.;
Höfle, G. Angew. Chem. Int. Ed. 1969, 8, 981; Angew.
Chem. 1969, 81, 1001. (c) Neises, B.; Steglich, W. Org.
Synth. 1985, 63, 183. (d) Xu, S.; Held, I.; Kempf, B.; Mayr,
H.; Steglich, W.; Zipse, H. Chem. Eur. J. 2005, 11, 4751.
(11) Synthesis of Compound 17: To a solution of 9 (15.7 mg,
68.0 μmol) in CH2Cl2 (1 mL) were added DMAP (0.64 mg,
5.26 μmol) and 16 (20.0 mg, 53.0 μmol). Then the solution
was cooled to 0 °C and DCC (11.9 mg, 58.0 μmol) was
added. The mixture was stirred at 0 °C for 10 min, then at r.t.
overnight. The precipitate was filtered off and the filtrate
was evaporated to dryness. The residue was diluted in
CH2Cl2 (5 mL) and washed once with 0.5 M HCl solution (2
mL) and once with sat. aq NaHCO3 solution. After drying
with MgSO4 the product was purified by flash
(b) Velten, R.; Klostermeyer, D.; Steffan, B.; Steglich, W.;
Kuschel, A.; Anke, T. J. Antibiot. 1994, 47, 1017. (c) Velten,
R.; Steglich, W.; Anke, T. Tetrahedron: Asymmetry 1994, 5,
1229. (d) Inchausti, A.; Yaluff, G.; De Arias, A. R.; Ferreira,
M. E.; Nakayama, H.; Schinini, A.; Lorenzen, K.; Anke, T.;
Fournet, A. Phytother. Res. 1997, 11, 193.
(2) (a) Suzuki, Y.; Ohara, A.; Sugaya, K.; Takao, K.-I.; Tadano,
K.-I. Tetrahedron 2001, 57, 7291. (b) Jauch, J. Eur. J. Org.
Chem. 2001, 473. (c) Reiser, U.; Jauch, J. Synlett 2001, 90.
(d) Jauch, J. Synlett 2001, 87. (e) Suzuki, Y.; Nishimaki, R.;
Ishikawa, M.; Murata, T.; Takao, K.-I.; Tadano, K.-I. J. Org.
Chem. 2000, 65, 8595. (f) Suzuki, Y.; Nishimaki, R.;
Ishikawa, M.; Murata, T.; Takao, K.-I.; Tadano, K.-I.
Tetrahedron Lett. 1999, 40, 7835. (g) Jauch, J. Synlett 1999,
1325. (h) Murata, T.; Ishikawa, M.; Nishimaki, R.; Tadano,
K.-I. Synlett 1997, 1291.
chromatography (petroleum ether–Et2O 1:1; silica gel, Rf
0.13 and 0.08) to yield 17 (27.0 mg, 46.0 μmol, 87.0%).
Specifications for one THP-diastereomer: 1H NMR (500
MHz, CDCl3): δ = 9.45 (s, 1 H, H-12), 7.10 (br d, J = 6.6 Hz,
1 H, H-7), 5.34 (s, 1 H, H-11), 5.25–5.31 (m, 1 H, H-2), 5.08
(br s, 1 H, H-1′′), 4.75 (br t, J = 6.2 Hz, 1 H, H-2′), 4.70 (br
s, 1 H, H-1), 3.88 (br s, 1 H, H-9), 3.82–3.88 (m, 1 H, H-
5′′ax), 3.56–3.61 (m, 1 H, H-5′′eq), 2.75 (d, J = 4.1 Hz, 1 H,
OH), 2.42–2.50 (m, 1 H, H-6ax), 2.20–2.30 (m, 1 H, H-6eq),
2.09 (s, 3 H, H-12′), 2.01–2.09 (m, 1 H, H-3ax), 1.49–1.85
(m, 10 H, H-3eq, H-3′, H-2′′, H-3′′, H-4′′), 1.37–1.45 (m, 2 H,
H-4′), 1.34 (s, 3 H, H-14), 1.23–1.32 (m, 10 H, H-5′, H-6′,
H-7′, H-8′, H-9′), 1.06 (s, 3 H, H-13), 0.88 (t, J = 7.1 Hz, 3
H, H-10′). 13C NMR (125 MHz, CDCl3): δ = 192.9 (C-12),
175.4 (C-15), 171.1 (C-11′), 169.7 (C-1′), 154.3 (C-7), 138.3
(C-8), 103.8 (C-11), 99.2 (C-1′′), 73.4 (C-2′), 71.4 (C-2),
67.4 (C-1), 61.6 (C-5′′), 52.7 (C-10), 46.6 (C-9), 39.5 (C-5),
37.4 (C-3), 33.5 (C-4), 33.4 (C-13), 31.8 (C-3′), 30.7 (C-8′),
29.7 (C-2′′), 29.3 (C-5′), 29.13 (C-6′), 29.11 (C-7′), 25.1 (C-
4′), 24.9 (C-4′′), 24.6 (C-6), 23.3 (C-14), 22.6 (C-9′), 20.5
(C-12′), 18.1 (C-3′′), 14.1 (C-10′). [α]20D –45.5 (CHCl3, c =
0.2). HRMS (ESI+): m/z [M + Na]+ calcd for C32H48O10Na:
615.3146; found: 615.3157.
(3) (a) Murakami, T.; Hirono, R.; Furusawa, K. Tetrahedron
2005, 61, 9233. (b) Adam, W.; Lazarus, M.; Schmerder, A.;
Humpf, H.-U.; Saha-Möller, C. R.; Schreier, P. Eur. J. Org.
Chem. 1998, 2013. (c) Döbler, C.; Beller, M.; Mehltretter,
G. Angew. Chem. Int. Ed. 1999, 38, 3026; Angew. Chem.
1999, 111, 3211 . (d) Aladro, F. J.; Guerra, F. M.; Massanet,
G. M. Tetrahedron Lett. 2000, 41, 3209. (e) Morrill, C.;
Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 2842. (f) Huang,
K.; Liu, H. W.; Dou, X.; Huang, M.-Y.; Jiang, Y.-Y. Polym.
Adv. Technol. 2003, 14, 364.
(4) For a similar use of MOM acetals, see, e.g.: Fürstner, A.;
Nagano, T.; Müller, C.; Seidel, G.; Müller, O. Chem. Eur. J.
2007, 13, 1452.
(5) Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
(6) For the preparation of THP acetals, see, for example: Parry,
R. J.; Burns, M. R.; Skae, P. N.; Pal, B. Bioorg. Med. Chem.
1996, 4, 1077.
(7) Synthesis of Compound 15: 3,4-Dihydro-2H-pyran (565
μL, 6.18 mmol) was added to a mixture of 14 (324 mg, 1.24
mmol) and pyridinium p-toluenesulfonate (31.0 mg, 0.124
mmol) in CH2Cl2 (5.0 mL) and the reaction mixture was
stirred at r.t. for 2 h. Sat. aq NaHCO3 solution was added.
Extraction with CH2Cl2, drying over MgSO4 and
(12) (a) Askin, D.; Angst, C.; Danishefsky, S. J. Org. Chem.
1987, 52, 622. (b) Prazeres, V. F. V.; Castedo, L.; González-
Bello, C. Eur. J. Org. Chem. 2008, 3991.
(13) Baars, S. M.; Hoberg, J. O. Carbohydr. Res. 2006, 341,
1680.
purification by flash chromatography (petroleum ether–
Et2O, 2:1; silica gel, Rf 0.18 and 0.24) led to 15 (348 mg, 1.00
mmol, 81.0%). Specifications for one THP-diastereomer (Rf
0.24): 1H NMR (500 MHz, CDCl3): δ = 9.47 (s, 1 H, H-12),
7.17 (br d, J = 6.4 Hz, 1 H, H-7), 6.18 (dt, J = 10.2, 1.8 Hz,
1 H, H-1), 5.88 (dt, J = 10.2, 4.0 Hz, 1 H, H-2), 5.53 (s, 1 H,
H-11), 5.07 (t, J = 2.8 Hz, 1 H, H-1′), 4.08 (dt, J = 11.1, 2.6
Hz, 1 H, H-5′ax), 3.65 (br d, J = 11.5 Hz, 1 H, H-5′eq), 3.20
(br s, 1 H, H-9), 2.55 (dm, J = 19.5 Hz, 1 H, H-6ax), 2.43
(ddm, J = 19.5, 12.5 Hz, 1 H, H-6eq), 2.00 (dd, J = 4.0, 2.1
Hz, 2 H, H-3), 1.82–1.93 (m, 1 H, H-3′ax), 1.80–1.63 (m, 5
H, H-5, H-2′, H-4′), 1.57–1.63 (m, 1 H, H-3′eq), 1.24 (s, 3 H,
H-14), 1.04 (s, 3 H, H-13). 13C NMR (125 MHz, CDCl3): δ
= 192.7 (C-12), 175.3 (C-15), 156.0 (C-7), 138.9 (C-8),
(14) Synthesis of Compound 21: Compound 10 (21.8 mg, 79.0
μmol) was diluted in toluene (900 μL). 2,4,6-
Trichlorobenzoyl chloride (10.4 μL, 67.0 μmol) and Et3N
(17.0 μL, 121 μmol) were added and the solution was stirred
for 2 h at r.t. After this a mixture of 20 (30 mg, 61.0 μmol)
and DMAP (9.6 mg, 79 μmol) in toluene (900 μL) was added
and the solution was stirred for 24 h at r.t.. Sat. aq NaHCO3
solution was added and extraction with EtOAc, drying over
MgSO4, filtration and evaporation afforded a yellow oil,
Synlett 2013, 24, 1410–1414
© Georg Thieme Verlag Stuttgart · New York

LETTER
which was purified by flash chromatography (petroleum
Total Synthesis of Mniopetals A, B, C and D
1413
H-11), 5.37 (ddd, J = 12.7, 4.0, 2.3 Hz, 1 H, H-2), 4.87 (dd,
J = 6.5, 6.5 Hz, 1 H, H-2′), 4.59 (br s, 1 H, H-1), 3.89 (br s,
1 H, H-9), 2.46 (dm, J = 19.5 Hz, 1 H, H-6ax), 2.24 (dm, J =
19.5 Hz, 1 H, H-6eq), 2.14 (s, 3 H, H-12′), 2.08 (dd, J = 12.6,
12.6 Hz, 1 H, H-3ax), 1.81–1.85 (m, 2 H, H-3′), 1.77 (dd, J =
12.7, 3.4 Hz, 1 H, H-5), 1.50 (dd, J = 12.2, 3.6 Hz, 1 H, H-
3eq), 1.37–1.44 (m, 2 H, H-4′), 1.33 (s, 3 H, H-14), 1.20–1.30
(m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.05 (s, 3 H, H-13),
0.88 (t, J = 7.1 Hz, 3 H, H-10′). 13C NMR (125 MHz,
ether–Et2O, 1:1; silica gel, Rf 0.13 and 0.09). Yield: 31 mg
(41.0 μmol, 67.9%). Specifications for one THP-
diastereomer (Rf 0.09): 1H NMR (500 MHz, CDCl3): δ =
9.43 (s, 1 H, H-12), 7.11 (br d, J = 6.4 Hz, 1 H, H-7), 5.86
(br s, 1 H, H-1), 5.31 (s, 1 H, H-11), 5.05 (br s, 1 H, H-1′′),
4.75 (s, 2 H, H-11′), 4.36 (ddd, J = 12.8, 4.1, 2.4 Hz, 1 H, H-
2), 4.22 (dd, J = 7.5, 5.0 Hz, 1 H, H-2′), 3.81–3.91 (m, 1 H,
H-5′′ax), 3.76 (ddd, J = 11.0, 6.3, 3.2 Hz, 1 H, H-12′a), 3.67
(ddd, J = 11.0, 5.6, 3.2 Hz, 1 H, H-12′b), 3.48–3.63 (m, 3 H,
H-5′′eq), 3.38 (s, 3 H, H-14′), 3.22 (br s, 1 H, H-9), 2.48 (ddd,
J = 19.1, 5.8, 3.0 Hz, 1 H, H-6ax), 2.18–2.29 (m, 1 H, H-6eq),
1.99–2.12 (m, 1 H, H-3′′ax), 1.38–1.85 (m, 12 H, H-3, H-5,
H-3′, H-4′, H-2′′, H-3′′eq, H-4′′), 1.31 (s, 3 H, H-14), 1.21–
1.31 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.05 (s, 3 H, H-
13), 0.86–0.90 (m, 3 H, H-10′), 0.86 (s, 9 H, t-Bu), 0.07 (s, 3
H, SiMe), 0.05 (s, 3 H, SiMe). 13C NMR (125 MHz, CDCl3):
δ = 192.4 (C-12), 175.2 (C-15), 170.7 (C-1′), 154.2 (C-7),
137.9 (C-8), 103.8 (C-11), 99.6 (C-1′′), 95.0 (C-11′), 75.4
(C-2′), 72.7 (C-1), 71.6 (C-13′), 67.6 (C-12′), 65.9 (C-2),
61.4 (C-5′′), 59.0 (C-14′), 52.2 (C-10), 47.4 (C-9), 43.0 (C-
3), 40.7 (C-5), 33.6 (C-13), 33.5 (C-4), 33.2 (C-3′), 31.9 (C-
8′), 29.5 (C-2′′), 29.33 (C-5′), 29.31 (C-6′), 29.25 (C-7′),
25.8 (t-Bu), 25.07 (C-4′), 25.05 (C-4′′), 24.7 (C-6), 23.5 (C-
14), 22.6 (C-9′), 18.3 (t-Bu), 17.6 (C-3′′), 14.1 (C-10′), –5.1
(SiMe), –5.3 (SiMe). [α]20D –25.3 (CHCl3, c = 0.3). HRMS
(ESI+): m/z [M + Na]+ calcd. for C40H68O11SiNa: 775.4423;
found: 775.4400.
CDCl3): δ = 193.3 (C-12), 175.9 (C-15), 171.7 (C-11′), 169.6
(C-1′), 154.8 (C-7), 138.5 (C-8), 99.6 (C-11), 73.0 (C-2′),
71.1 (C-2), 68.1 (C-1), 53.4 (C-10), 46.2 (C-9), 39.7 (C-5),
37.5 (C-3), 33.6 (C-4), 33.3 (C-13), 31.8 (C-8′), 30.9 (C-3′),
29.3 (C-5′), 29.14 (C-6′), 29.11 (C-7′), 25.1 (C-4′), 24.7 (C-
6), 23.3 (C-14), 22.6 (C-9′), 20.7 (C-12′), 14.1 (C-10′). [α]20
D
–64.0 (CHCl3, c = 0.4); Lit.1b [α]20D –63 (CHCl3, c = 0.05).
HRMS (ESI+): m/z [M + Na]+ calcd for C27H40O9Na:
531.2570; found: 531.2563.
Mniopetal B (1b): 1H NMR (500 MHz, CDCl3): δ = 9.46 (s,
1 H, H-12), 7.18 (br d, J = 6.5 Hz, 1 H, H-7), 5.52 (br s, 1 H,
H-11), 5.40 (ddd, J = 12.6, 4.0, 2.4 Hz, 1 H, H-2), 4.56 (br s,
1 H, H-1), 4.49 (br s, 1 H, OH), 4.18 (br s, 1 H, H-2′), 3.85
(br s, 1 H, H-9), 2.99 (br s, 1 H, OH), 2.92 (br s, 1 H, OH),
2.49 (dddm, J = 19.5, 6.7, 3.9 Hz, 1 H, H-6ax), 2.26 (ddm, J
= 19.5, 12.9 Hz, 1 H, H-6eq), 2.02 (ddd, J = 12.6, 12.6, 6.7
Hz, 1 H, H-3ax), 1.77 (dd, J = 12.6, 3.3 Hz, 1 H, H-5), 1.68–
1.74 (m, 1 H, H-3′a), 1.62–1.67 (m, 1 H, H-3′b), 1.55–1.59
(m, 1 H, H-3eq), 1.37-1.43 (m, 2 H, H-4′), 1.35 (s, 3 H, H-14),
1.20–1.30 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-9′), 1.07 (s, 3
H, H-13), 0.88 (t, J = 6.8 Hz, 3 H, H-10′). 13C NMR (125
MHz, CDCl3): δ = 193.2 (C-12), 175.7 (C-15), 174.4 (C-1′),
154.9 (C-7), 138.1 (C-8), 99.4 (C-11), 71.4 (C-2), 70.6 (C-
2′), 68.8 (C-1), 53.4 (C-10), 46.2 (C-9), 39.6 (C-5), 37.4 (C-
3), 34.5 (C-3′), 33.7 (C-4), 33.3 (C-13), 31.8 (C-8′), 29.4 (C-
5′), 29.3 (C-6′), 29.2 (C-7′), 24.8 (C-4′), 24.7 (C-6), 23.2 (C-
14), 22.7 (C-9′), 14.1 (C-10′). [α]20D –47.3 (CHCl3, c = 0.1);
Lit.1b [α]20D –46 (CHCl3, c = 0.05). HRMS (ESI+): m/z [M +
Na]+ calcd for C25H38O8Na: 489.2465; found: 489.2475.
Mniopetal C (1c): 1H NMR (500 MHz, CDCl3): δ = 9.44 (s,
1 H, H-12), 7.14 (br d, J = 6.8 Hz, 1 H, H-7), 5.51 (br s, 1 H,
H-11), 5.38 (ddd, J = 12.7, 4.0, 2.3 Hz, 1 H, H-2), 4.56 (br s,
1 H, H-1), 4.18 (dd, J = 7.5, 4.1 Hz, 1 H, H-2′), 3.83 (br s, 1
H, H-9), 2.48 (ddd, J = 18.6, 6.0, 3.0 Hz, 1 H, H-6ax), 2.25
(ddm, J = 19.0, 12.5 Hz, 1 H, H-6eq), 2.04 (dd, J = 12.6, 12.6
Hz, 1 H, H-3ax), 1.76 (dd, J = 12.2, 3.9 Hz, 1 H, H-5), 1.69–
1.75 (m, 1 H, H-3′a), 1.63–1.68 (m, 1 H, H-3′b), 1.55 (dd, J =
12.3, 4.2 Hz, 1 H, H-3eq), 1.38–1.44 (m, 2 H, H-4′), 1.34 (s,
3 H, H-14), 1.24–1.33 (m, 6 H, H-5′, H-6′, H-7′), 1.06 (s, 3
H, H-13), 0.88 (t, J = 6.8 Hz, 3 H, H-8′). 13C NMR (125
MHz, CDCl3): δ = 194.3 (C-12), 175.9 (C-15), 174.4 (C-1′),
155.1 (C-7), 135.2 (C-8), 99.5 (C-11), 71.3 (C-2), 70.7 (C-
2′), 68.6 (C-1), 53.5 (C-10), 46.2 (C-9), 39.6 (C-5), 37.4 (C-
3), 34.4 (C-3′), 33.7 (C-4), 33.2 (C-13), 31.6 (C-6′), 28.9 (C-
5′), 24.8 (C-4′), 24.7 (C-6), 23.2 (C-14), 22.5 (C-7′), 14.0 (C-
8′). [α]20D –47.3 (CHCl3, c = 0.1); Lit.1b [α]20D –45 (CHCl3, c
= 0.05). HRMS (ESI+): m/z [M + Na]+ calcd for C23H34O8Na:
461.2152; found: 461.2150.
(15) (a) Trost, B. M.; Caldwell, C. G.; Murayama, E.; Heissler,
D. J. Org. Chem. 1983, 48, 3252. (b) Carreira, E. M.; Bois,
J. D. J. Am. Chem. Soc. 1995, 117, 8106.
(16) Cleavage of the Silyl Protection Group in 21: Compound
21 (30.0 mg, 40.0 μmol) was diluted in HF·pyridine (1.14
mL, 1.59 mmol) in THF–pyridine prepared according to a
procedure of Trost’s (see ref. 15a). The solution was stirred
at r.t. for 24 h. Sat. aq NaHCO3 solution was added.
Extraction with EtOAc, drying over MgSO4, filtration and
evaporation afforded a yellow oil, which was purified by
flash chromatography (petroleum ether–acetone, 5:1; silica
gel, Rf 0.12). Yield: 20.0 mg (31.0 μmol, 79.0%).
Specifications for one THP-diastereomer: 1H NMR (500
MHz, CDCl3): δ = 9.47 (s, 1 H, H-12), 7.11 (d, J = 6.5 Hz, 1
H, H-7), 5.76 (s, 1 H, H-1), 5.40 (s, 1 H, H-11), 4.96 (br s, 1
H, H-1′′), 4.67–4.77 (m, 2 H, H-11′), 4.29–4.39 (m, 1 H, H-
2), 4.21–4.28 (m, 1 H, H-2′), 3.93 (dd, J = 11.4, 2.5 Hz, 1 H,
H-5′′ax), 3.69–3.77 (m, 1 H, H-12′a), 3.56–3.62 (m, 1 H, H-
12′b), 3.53–3.56 (m, 1 H, H-5′′eq), 3.45–3.50 (m, 2 H, H-13′),
3.32 (s, 3 H, H-14′), 3.30 (br s, 1 H, H-9), 2.44 (dm, J = 19.3
Hz, 1 H, H-6ax), 2.14–2.26 (m, 1 H, H-6eq), 1.82 (d, J = 3.3
Hz, 1 H, OH), 1.66–1.77 (m, 4 H, H-3′, H-2′′), 1.47–1.65 (m,
7 H, H-3, H-5, H-3′′, H-4′′), 1.33–1.44 (m, 2 H, H-4′), 1.24
(s, 3 H, H-14), 1.16–1.27 (m, 10 H, H-5′, H-6′, H-7′, H-8′, H-
9′), 1.00 (s, 3 H, H-13), 0.81 (t, J = 7.0 Hz, 3 H, H-10′). 13
C
NMR (125 MHz, CDCl3): δ = 192.2 (C-12), 175.0 (C-15),
172.2 (C-1′), 153.8 (C-7), 137.8 (C-8), 99.9 (C-11), 94.9 (C-
11′), 94.4 (C-1′′), 75.4 (C-2′), 72.9 (C-1), 71.7 (C-13′), 67.6
(C-12′), 65.7 (C-2), 61.2 (C-5′′), 59.0 (C-14′), 52.3 (C-10),
45.9 (C-9), 41.6 (C-5), 41.1 (C-3), 33.6 (C-13), 33.5 (C-4),
33.0 (C-3′), 31.9 (C-8′), 29.8 (C-2′′), 29.4 (C-5′), 29.3 (C-6′),
29.2 (C-7′), 25.1 (C-4′), 25.0 (C-4′′), 24.7 (C-6), 23.4 (C-14),
22.6 (C-9′), 17.5 (C-3′′), 14.1 (C-10′). [α]20D –32.1 (CHCl3,
c = 1.2). HRMS (ESI+): m/z [M + Na]+ calcd for
Mniopetal D (1d): 1H NMR (500 MHz, CDCl3): δ = 9.46 (s,
1 H, H-12), 7.16 (br d, J = 6.6 Hz, 1 H, H-7), 5.84 (br s, 1 H,
H-1), 5.50 (s, 1 H, H-11), 4.49 (s, 1 H, OH), 4.39–4.44 (m, 1
H, H-2), 4.29–4.33 (m, 1 H, H-2′), 3.27 (br s, 1 H, H-9), 2.75
(d, J = 5.7 Hz, 1 H, OH), 2.52 (ddd, J = 19.6, 6.7, 3.3 Hz, 1
H, H-6ax), 2.27 (ddd, J = 19.7, 12.8, 2.5 Hz, 1 H, H-6eq), 1.95
(d, J = 2.8 Hz, 1 H, OH), 1.80–1.88 (m, 1 H, H-3′a), 1.57–
1.73 (m, 4 H, H-3, H-5, H-3′b), 1.44–1.54 (m, 2 H, H-4′),
C34H54O11Na: 661.3564; found: 661.3549.
(17) Mniopetal A (1a): 1H NMR (500 MHz, CDCl3): δ = 9.44 (s,
1 H, H-12), 7.12 (br d, J = 6.7 Hz, 1 H, H-7), 5.48 (br s, 1 H,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1410–1414

1414
J. Weihrather, J. Jauch
LETTER
1.32 (s, 3 H, H-14), 1.23–1.30 (m, 10 H, H-5′, H-6′, H-7′, H-
8′, H-9′), 1.08 (s, 3 H, H-13), 0.87 (t, J = 7.1 Hz, 3 H, H-10′).
13C NMR (125 MHz, CDCl3): δ = 192.6 (C-12), 176.1 (C-
15), 174.4 (C-1′), 154.6 (C-7), 137.5 (C-8), 99.3 (C-11), 74.5
(C-1), 70.6 (C-2′), 65.2 (C-2), 52.3 (C-10), 47.0 (C-9), 41.3
(C-3), 40.8 (C-5), 34.6 (C-3′), 33.53 (C-4), 33.49 (C-13),
31.8 (C-8′), 29.4 (C-5′), 29.3 (C-6′), 29.1 (C-7′), 24.7 (C-6),
24.5 (C-4′), 23.4 (C-14), 22.6 (C-9′), 14.1 (C-10′). [α]20
D
–36.6 (CHCl3, c = 0.1); Lit.1b [α]20D –40 (CHCl3, c = 0.05).
HRMS (ESI+): m/z [M + Na]+ calcd for C25H38O8Na:
489.2465; found: 489.2434.
Synlett 2013, 24, 1410–1414
© Georg Thieme Verlag Stuttgart · New York

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