LETTER
123
An Enantiospecific Formal Total Synthesis of the 5-8-5 Tricyclic Diterpene
ent-Fusicoauritone
TotalSynthesi ofthe5-85TrSrikrishna,*
A.
icycli Diterpen ent-Fusicoauritone
Gopalasetty Nagaraju
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Fax +91(80)3600683; E-mail: askiisc@gmail.com
Received 26 October 2011
Dedicated to Professor T. N. Guru Row on the occasion of his 60th birthday
HO
O
H
H
H
O
anadensin
fusicoauritone (2)
Key words: fusicoccanes, limonene, enantiospecific synthesis, cyclooctanoids, ring-closing metathesis
12
C
H
15
19
18
1
10
Since the first report on the structure elucidation of fusicoccin A,1 several diterpenes containing the 5-8-5 tricyclic
fusicoccane framework 1 have been isolated from a variety of natural sources, including the wax secretions of
scale insects, fungi, liverworts, and from higher plants.2
Members of the fusicoccane family exhibit significant
phytohormonal activities. For example, fusicoccin stabilizes the protein–protein interaction between the autoinhibitory region of the plant plasma membrane H+-ATPase
and a 14-3-3 protein, and the cotylenins induce differentiation in murine and human myeloid leukemia cells.3 Although fusicoccin and cotylenins have oxygen
functionalities in the B ring, a number of fusicoccanes was
found to contain oxygen functionalities only in the A ring,
such as anadensin, fusicogigantanones, fusicoauritone,
etc. (Figure 1). Isolation of fusicoauritone (2) was first
reported2d in 1994 from the liverwort Anastrophyllum auritum collected in Ecuador. Subsequently, it was found in
several liverworts, and recently2g from the Argentine liverwort Porella chilensis along with three of its regioisomers.
OH
B
4
A
6
8
20
fusicoccane (1)
O
O
O
H
fusicogigantanone A
H
H
O
fusicogigantanone B
Figure 1
interest in the chiral-pool-based synthesis of natural products starting from the readily available monoterpene (R)limonene,7 we herein report an enantiospecific approach
to fusicoauritone (2), starting from 5-isopropyl-2-methylcyclopent-1-enemethanol (3) employing two ring-closing-metathesis (RCM) reactions for the construction of
the B and A rings.
In the past three decades, research activity in the synthesis
of the carbocyclic systems in which a cyclooctane forms
a part of the polycyclic system have proliferated rapidly.4
The main challenge in the synthesis of fusicoccanes is the
stereocontrolled construction of the 5-8-5 tricyclic system, in particular the eight-membered B ring.5 So far there
has been only one report in the literature on the synthesis
of fusicoauritone (2). In 2007, Williams and co-workers
reported6 the enantiospecific first total synthesis of fusicoauritone (2) employing a Nazarov cyclization of a dolabellane system as the key step. In continuation of our
It was considered (Scheme 1) that the cyclopentenemethanol 3, readily available7i from dihydrolimonene (4),
could serve as the C ring of fusicoauritone (2). Cyclopentannulation at the C-3–C-4 bond of the bicyclo[6.3.0]undecenone 5 was contemplated for the construction of the
5-8-5 tricyclic system of fusicoccanes, which could be
subsequently transformed into fusicoauritone (2). An
RCM reaction of a decadiene, for example, 6 was conceived for the construction of the bicyclic enone 5. It was
considered that the decadiene 6 could be obtained by elaboration of the exo-methylene and hydroxyethyl groups in
the cyclopentylethanol 7, which contains the methyl and
isopropyl groups cis to each other as required for the fusicoccanes. Synthesis of the alcohol 7 from the readily
available monoterpene limonene via dihydrolimonene 4
has already been well established.7i
SYNLETT 2012, 23, 123–127xx. 201
Advanced online publication: 09.12.2011
DOI: 10.1055/s-0031-1290095; Art ID: D26211ST
© Georg Thieme Verlag Stuttgart · New York
The synthetic sequence is depicted in Scheme 2 and
Scheme 3. To begin with, the primary alcohol 7 was obtained from dihydrolimonene 4 in five steps, via the
Johnson orthoester Claisen rearrangement8 of the cyclopentenylmethanol 3, followed by reduction of the result-
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Abstract: An enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene fusicoauritone has been accomplished, starting
from 5-isopropyl-2-methylcyclopent-1-enemethanol [available in
three steps from (R)-dihydrolimonene] employing two ring-closingmetathesis reactions for the construction of the eight- and fivemembered rings.
LETTER
A. Srikrishna, G. Nagaraju
O
OR
C
A
OH 75%
B
H
OR
a
O
OH
H
H
5
ent-fusicoauritone (ent-2)
4
6
3
7R=H
8 R = Bn
c
OBn
OH
3
OBn
X
COOEt
7
Scheme 1
11
9 X = H, OH d 87%
10 X = O
f 98%
ant ester in a highly stereoselective manner.7i For the
generation of a deca-1,9-diene system, the precursor of
the RCM reaction,9 the alkoxyethyl group in 7 needs to be
extended by two carbons and the exo-methylene group by
three carbons.
First the primary alcohol in 7 was protected as its benzyl
ether by treating with sodium hydride and benzyl chloride
in THF in the presence of a catalytic amount of tetrabutylammonium iodide (TBAI) to furnish the ether 8. Hydroboration with in situ generated borane–THF complex
followed by oxidation with alkaline hydrogen peroxide
transformed the benzyl ether 8 into the primary alcohol 9
in 79% yield in a highly stereoselective manner, via approach of the borane from the less hindered face (anti to
both the bulky groups).6 Oxidation of the primary alcohol
9 with pyridinium chlorochromate (PCC) and silica gel in
dichloromethane at room temperature followed by Horner–Wadsworth–Emmons reaction of the aldehyde 10
with triethyl phosphonoacetate and sodium hydride in
THF generated the (E)-propenoate 11 in ca. 70% yield. Simultaneous reduction of the olefin as well as cleavage of
the benzyl ether with 10% palladium over carbon as the
catalyst at one atmosphere pressure (balloon) of hydrogen
transformed the unsaturated ester 11 into the saturated hydroxyester 12 in quantitative yield. Prior to the conversion
of the ester in 12 into a terminal olefin, the hydroxyethyl
group was modified into a 3-hydroxybutenyl group. Thus,
oxidation of the primary alcohol in 12 with PCC and silica
gel in dichloromethane at room temperature, followed by
Grignard reaction of the resultant aldehyde 13 with vinylmagnesium bromide at low temperature furnished a 1:1
epimeric mixture of the allyl alcohol 14. Protection of the
alcohol in 14 with tert-butyldimethylsilyl chloride and
imidazole furnished the TBDMS ether 15, which on reduction with LAH generated the primary alcohol 16 in
91% yield. Oxidation of the primary alcohol 16 with PCC
in dichloromethane in the presence of 4 Å molecular
sieves furnished the aldehyde 17, which on Wittig reaction with methylenetriphenylphosphorane, generated the
decadiene system 18 in 79% yield. Treatment of the diene
18
with
10
mol%
of
Grubbs
catalyst
[Cl2(Cy3P)2Ru=CHPh] in dichloromethane at room temperature cleanly generated the 5-8 bicyclic system 19 of
the fusicoccanes in 90% yield. Tetrabutylammonium
Synlett 2012, 23, 123–127
79%
e
80%
OH
4
b 94%
OR
X
h
88%
COOEt
COOEt
12 X = H, OH
13 X = O
g 87%
14 R = H
15 R = TBDMS
j
OR
i 96%
96%
OTBDMS
m
90%
X
H
o, 88%
19 R = TBDMS
n 96%
20 R = H
O
16 X = H, OH k 91%
17 X = O
l 87%
18 X = CH2
H
5
Scheme 2 Reagents and conditions: (a) ref. 7i; (b) NaH, BnCl,
TBAI (cat.), THF, 0 °C to r.t., 4 h; (c) NaBH4, BF3·OEt2, THF, 0 °C
to r.t.; 30% H2O2, 3 N NaOH, 0 °C to r.t., 8 h; (d) PCC, silica gel,
CH2Cl2, r.t., 1 h; (e) NaH, (EtO)2P(O)CH2COOEt, THF, 0 °C to r.t.,
3 h; (f) H2 (1 atm), 10% Pd/C, MeOH, r.t., 6 h; (g) PCC, silica gel,
CH2Cl2, r.t., 1 h; (h) CH2=CHMgBr, THF, –70 °C, 0.5 h; (i)
TBDMSCl, imidazole, DMAP, CH2Cl2, r.t., 3 h; (j) LAH, Et2O, 0 °C
to r.t., 0.3 h; (k) PCC, 4 Å MS, CH2Cl2, r.t., 1 h; (l) Ph3P+MeBr–, KOtAm, C6H6, r.t., 1.5 h; (m) Cl2(Cy3P)2Ru=CHPh, CH2Cl2, r.t., 24 h; (n)
TBAF, THF, 0 °C to r.t., 6 h; (o) PCC, silica gel, CH2Cl2, r.t., 1.5 h.
fluoride (TBAF)-mediated deprotection of the silyl group
followed by oxidation of the resultant allyl alcohol 20
with PCC and silica gel in dichloromethane at room temperature furnished the enone 5 in 84% yield, whose structure was established from its spectroscopic data.10
A cuprate reaction was chosen for the simultaneous introduction of a secondary methyl group at the C-5 and an allyl group at the C-4 position of the enone 5. Thus,
treatment of the enone 5 with lithium dimethylcopper in
diethyl ether followed by treatment of the resultant enolate with allyl bromide furnished the bicyclic ketone 21 in
60% yield, in a highly stereoselective manner.10 The stereochemistry of the methyl group was tentatively assigned
on the basis of the approach of the nucleophile from the
less hindered face of the preferred boat conformation of
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124
125
Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone
the eight-membered ring in the enone 5, and that of the allyl group was assigned trans to the methyl group, and both
stereochemistries were confirmed at a later stage. For the
construction of the third ring, a Wacker oxidation followed by intramolecular aldol condensation was initially
explored. Reaction of the bicyclic ketone 21 with cuprous
chloride and palladium chloride in DMF and water in an
oxygen atmosphere (balloon) furnished the dione 22 in
68% yield which, on treatment with potassium hydroxide
in refluxing aqueous methanol, generated the norfusicoccane (23) in 80% yield. However, the enone 23 was found
to be a ca. 1:1 epimeric mixture (confirmed by 1H and 13C
NMR spectroscopy), presumably due to the basic conditions of the reaction. Hence an alternative RCM-based sequence was explored for the construction of the A ring of
fusicoauritone (2). Grignard reaction of the bicyclic ketone 21 with vinylmagnesium bromide furnished an
epimeric mixture of the allyl alcohol 24 in 67% yield.
An RCM reaction of the diene 24 with 5 mol% Grubbs
second-generation catalyst 25, followed by oxidation of
the resultant cyclopentenol11 with PCC and silica gel in
dichloromethane at room temperature furnished the enone
23a. The structure of norhydroxynorfusicoauritone (23a)
was established from its spectroscopic data,10 and the stereochemistry at all the stereocenters was confirmed by
single-crystal X-ray diffraction analysis.10 An ORTEP
diagram is depicted in Figure 2.
O
O
a
60%
H
H
5
21
b
O
68%
O
O
c
H
(1:1)
80%
H
H
23
22
O
HO
d
e,f
67%
50%
21
H
H
H
24
23a
OH
HO
g
h
95%
65%
21
H
H
H
27
26
i 86%
O
j
N
N
Ru
Cl
Ph
PCy3
Cl
2
H
H
28
25
Figure 2
ORTEP diagram of the enone 23a
The same strategy was extended to the completion of the
synthesis of fusicoauritone (2). Thus, Grignard reaction of
the bicyclic ketone 21 with isopropenylmagnesium bromide furnished the allyl alcohol 26 in 95% yield. An RCM
reaction of the diene 26 with 5 mol% Grubbs second-generation catalyst 25 in dichloromethane at room temperature, followed by treatment of the resultant mixture with
silica gel in moist dichloromethane generated the transposed allyl alcohol 27. Finally, oxidation of the alcohol 28
with pyridinium dichromate (PDC) in dichloromethane at
room temperature furnished norhydroxyfusicoauritone
(28), whose structure was established from its spectroscopic data10 and was confirmed by comparison the 1H
NMR spectrum reported by Williams and co-workers.6
Synthesis of the enone 28 constitutes a formal total synthesis of fusicoauritone (2), as further oxidation of the
enone 28 (along with its C-6 epimer) into fusicoauritone 2
by tert-butylhypochlorite has already been reported by
Williams and co-workers.6
© Thieme Stuttgart · New York
Scheme 3 Reagents and conditions: (a) CuI, MeLi, Et2O, HMPA,
r.t.; CH2=CHCH2Br, –30 °C to r.t., 9 h; (b) CuCl, PdCl2, DMF, H2O,
O2, r.t., 3.5 h; (c) 10% aq KOH, MeOH, reflux, 10 h; (d) CH2=CHMgBr, THF, r.t., 6 h; (e) Grubbs cat. 25 (5 mol%), CH2Cl2, r.t., 3.5 h; (f)
PCC, silica gel, CH2Cl2, r.t., 2 h; (g) CH2=C(Me)MgBr, THF, r.t., 9
h; (h) i. Grubbs cat. 25 (5 mol%), CH2Cl2, r.t., 7 h; ii. CH2Cl2 (moist),
silica gel, 1 h; (i) PDC, CH2Cl2, r.t., 2.5 h; (j) ref. 6.
In conclusion, we have developed an enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene entfusicoauritone (2). Starting from the readily available [in
three steps from (R)-dihydrolimonene 4] 5-isopropyl-2methylcyclopent-1-enemethanol [(S)-3], the synthesis of
the enone (+)-28 [precursor of fusicoauritone (2)] was accomplished in 20 steps in an overall yield of 5.1% (with
an average yield of ca. 87% for each step), which is marginally better than the 22-step conversion (ca. 5% overall
yield) of (R)-3 into the enone (–)-28 by Williams et al.6
Two RCM reactions were employed for the construction
of the eight- and five-membered rings A and B, respectively, of fusicoccane. Extension of the strategy for the
enantiospecific synthesis of other fusicoccane natural
products is currently in progress.
Synlett 2012, 23, 123–127
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LETTER
A. Srikrishna, G. Nagaraju
Acknowledgment
We thank the CCD Facility, Indian Institute of Science, and Mr.
Ravish S., for the X-ray diffraction analysis, and the CSIR, New
Delhi, for the award of a research fellowship to G.N.
References and Notes
(1) (a) Barrow, K. D.; Barton, D. H. R.; Chain, E.; Conlay, C.;
Smale, T. C.; Thomas, R.; Waight, E. S. J. Chem. Soc. C.
1971, 1259. (b) Barrow, K. D.; Barton, D. H. R.; Chain, E.;
Ohnsorge, U. F. W.; Thomas, R. J. Chem. Soc. C 1971,
1265.
(2) (a) Tassa, T.; Togashi, M. Agric. Biol. Chem. (Japan) 1973,
37, 1505. (b) Huneck, S.; Baxter, G.; Cameron, A. F.;
Connolly, J. D.; Rycroft, D. S. Tetrahedron Lett. 1983, 24,
3787. (c) Asakawa, Y.; Lin, X.; Tori, M.; Kondo, K.
Phytochemistry 1990, 29, 2597. (d) Zapp, J.; Burkhardt, G.;
Becker, H. Phytochemistry 1994, 37, 787. (e) Liu, H.-J.;
Wu, C.-L.; Becker, H.; Zapp, J. Phytochemistry 2000, 53,
845. (f) Komala, I.; Ito, T.; Nagashima, F.; Yagi, Y.;
Kawahata, M.; Yamaguchi, K.; Asakawa, Y.
Phytochemistry 2010, 71, 1387. (g) Gilabert, M.; Ramos,
A. N.; Schiavone, M. M.; Arena, M. E.; Bardon, A. J. Nat.
Prod. 2011, 74, 574.
(3) For detailed biological profiles of fusicoccins, see references
cited in: Richter, A.; Hedberg, C.; Waldmann, H. J. Org.
Chem. 2011, 76, 6694.
(4) (a) Mehta, G.; Singh, V. Chem. Rev. 1999, 99, 881.
(b) Petasis, N. A.; Patane, M. A. Tetrahedron 1992, 48,
5757.
(5) Dake, G. R.; Fenster, E. E.; Patrick, B. O. J. Org. Chem.
2008, 73, 6711; and references cited therein.
(6) Williams, D. R.; Robinson, L. A.; Nevill, C. R.; Reddy, J. P.
Angew. Chem. Int. Ed. 2007, 46, 915.
(7) (a) Srikrishna, A.; Babu, N. C. Tetrahedron Lett. 2001, 42,
4913. (b) Srikrishna, A.; Babu, N. C.; Dethe, D. H. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2003, 42,
1688. (c) Srikrishna, A.; Dethe, D. H. Org. Lett. 2003, 5,
2295. (d) Srikrishna, A.; Babu, N. C.; Rao, M. S.
Tetrahedron 2004, 60, 2125. (e) Srikrishna, A.; Pardeshi, V.
H.; Satyanarayana, G. Tetrahedron: Asymmetry 2010, 21,
746. (f) Srikrishna, A.; Pardeshi, V. H. Tetrahedron 2010,
66, 6810. (g) Srikrishna, A.; Pardeshi, V. H.; Mahesh, K.
Tetrahedron: Asymmetry 2010, 21, 2512. (h) Srikrishna, A.;
Pardeshi, V. H.; Mahesh, K. Tetrahedron: Asymmetry 2010,
21, 2830. (i) Srikrishna, A.; Nagaraju, G.; Ravi, G. Synlett
2010, 3015. (j) Srikrishna, A.; Nagaraju, G. Indian J. Chem.,
Sect. B: Org. Chem. Incl. Med. Chem. 2011, 50, 73.
(k) Srikrishna, A.; Dethe, D. H. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 2011, 50, 1092.
(l) Srikrishna, A.; Seth, V. M.; Nagaraju, G. Synlett 2011,
2343.
(8) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom,
T. J.; Li, T.-t.; Faulkner, D. J.; Petersen, R. J. Am. Chem. Soc.
1970, 92, 741.
(9) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(b) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39, 3013.
(c) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18. (d) Grubbs, R. H. Tetrahedron 2004, 60, 7117.
(10) Yields refer to isolated and chromatographically pure
compounds. All the compounds exhibited spectroscopic data
(IR, 1H NMR, 13C NMR, and HRMS) consistent with their
structures.
Selected Spectroscopic Data for (1S,8R,9S)-9-Isopropyl1-methylbicyclo[6.3.0]undec-4-en-3-one (5)
[a]D26 –196.6 (c 1.4, CHCl3). IR (neat): nmax = 3019, 1660
Synlett 2012, 23, 123–127
LETTER
(C=O), 1388, 1369, 1243, 1202, 1152, 839, 768 cm–1. 1H
NMR (400 MHz, CDCl3): d = 6.49–6.33 (1 H, m, H-3), 6.19
(1 H, d, J = 12.0 Hz, H-4), 2.81 (1 H, d, J = 12.2 Hz, H-2A),
2.90–2.75 (1 H, m), 2.48 (1 H, d, J = 12.0 Hz, H-2B), 2.60–
2.34 (1 H, m), 2.04–1.25 (9 H, m), 0.97 (3 H, s, t-CH3), 0.90–
0.85 [6 H, m, CH(CH3)2]. 13C NMR (100 MHz, CDCl3): d =
201.2 (C, C=O), 148.2 (CH, C-5), 137.0 (CH, C-4), 54.2
(CH2, C-2), 46.5 (CH, C-8), 42.1 (CH, C-9), 41.7 (C, C-1),
39.3 (CH2), 29.3 (CH), 25.8 (CH2), 24.3 (CH3), 23.9 (CH2),
22.2 (CH2), 21.8 (CH3), 20.4 (CH3). HRMS: m/z calcd for
C15H24ONa [M + Na]: 243.1725; found: 243.1733.
(1S,4S,5R,8R,9S)-4-Allyl-9-isopropyl-1,5-dimethylbicyclo[6.3.0]undecan-3-one (21)
[a]D21 +84.2 (c 2.9, CHCl3). IR (neat): nmax = 3078, 1694
(C=O), 1386, 1302, 992, 913 cm–1. 1H NMR (400 MHz,
CDCl3 + CCl4): d = 5.64 (1 H, ddt, J = 17.7, 9.9, 7.5 Hz,
CH=CH2), 4.95 (1 H, d, J = 17.7 Hz, CH=CH2), 4.93 (1 H,
d, J = 9.9 Hz, CH=CH2), 2.46 (1 H, d, J = 11.2 Hz, H-2A),
2.54–2.35 (1 H, m), 2.24–1.76 (6 H, m), 1.76–1.22 (9 H, m),
1.01 (3 H, d, J = 6.7 Hz, s-CH3), 0.87 (3 H, s, t-CH3), 0.87
[3 H, d, J = 6.4 Hz, CH(CH3)2], 0.79 [3 H, d, J = 6.7 Hz,
CH(CH3)2]. 13C NMR (100 MHz, CDCl3 + CCl4): d = 214.8
(C, C=O), 135.8 (CH, CH=CH2), 116.3 (CH2, CH=CH2),
62.7 (CH, C-4), 53.0 (CH2, C-2), 47.4 (CH), 46.8 (CH), 44.8
(C, C-1), 42.6 (CH2), 35.8 (CH2), 34.6 (CH2), 31.2 (CH),
28.1 (CH), 24.4 (CH2), 24.2 (CH3), 22.5 (CH2), 21.6 (CH3),
19.9 (CH3), 19.8 (CH3). HRMS: m/z calcd for C19H32ONa
[M + Na]: 299.2351; found: 299.2350.
(1S,7S,8R,11R,12S)-12-Isopropyl-1,8-dimethyltricyclo[9.3.0.03,7]tetradec-3-en-5-one (23a)
Mp 78–80 °C; [a]D22 +3.28 (c 0.5, CHCl3). IR (neat): nmax =
1700 (C=O), 1606, 1388, 1342, 1277, 1239, 1187, 918 cm–1.
1
H NMR (400 MHz, CDCl3): d = 5.89 (1 H, s, C=CH), 2.75
(1 H, d, J = 12.6 Hz, H-2A), 2.66 (1 H, dd, J = 18.8, 6.3 Hz,
H-6A), 2.39 (1 H, d, J = 12.6 Hz, H-2B), 2.45–2.38 (1 H, m),
2.08 (1 H, d, J = 18.8 Hz, H-6B), 2.05–1.25 (12 H, m), 1.05
(3 H, d, J = 6.7 Hz, s-CH3), 0.95 (3 H, s, t-CH3), 0.86 [3 H,
d, J = 6.8 Hz, CH(CH3)2], 0.83 [3 H, d, J = 6.8 Hz,
CH(CH3)2]. 13C NMR (100 MHz, CDCl3): d = 209.0 (C,
C=O), 183.3 (C, C-3), 133.4 (CH, C-4), 53.5 (CH), 47.1
(CH), 44.5 (C), 44.3 (CH2), 44.1 (CH2), 42.0 (CH), 39.8
(CH), 39.5 (CH2), 31.5 (CH2), 28.3 (CH), 26.3 (CH2), 25.1
(CH3), 24.3 (CH3), 23.6 (CH2), 22.7 (CH3), 20.0 (CH3).
HRMS: m/z calcd for C19H30ONa [M + Na]: 297.2194;
found: 297.2198.
(1S,7S,8R,11R,12S)-12-Isopropyl-1,4,8-trimethyltricyclo[9.3.0.03,7]tetradec-3-en-5-one (28)
Mp 92–94 °C; [a]D22 +14.83 (c 1.6, CHCl3). IR (KBr):
nmax = 1699 (C=O), 1376, 1347, 1326, 1156, 1083 cm–1. 1H
NMR (400 MHz, CDCl3): d = 2.87 (1 H, d, J = 13.0 Hz, H2A), 2.63 (1 H, dd, J = 18.8, 6.2 Hz, H-6A), 2.31 (1 H, d,
J = 13.0 Hz, H-2B), 2.28–2.18 (1 H, m), 2.05 (1 H, dd, J =
18.8, 2.6 Hz, H-6B), 2.00–1.80 (2 H, m), 1.72 (3 H, s,
olefinic CH3), 1.72–1.22 (10 H, m), 1.04 (3 H, d, J = 6.7 Hz,
s-CH3), 0.97 (3 H, s, t-CH3), 0.85 [3 H, d, J = 6.8 Hz
CH(CH3)2], 0.83 [3 H, d, J = 6.8 Hz, CH(CH3)2]. 13C NMR
(100 MHz, CDCl3): d = 209.2 (C, C=O), 174.5 (C, C-3),
139.4 (C, C-4), 52.6 (CH), 47.0 (CH), 46.1 (C), 42.9 (CH2),
42.7 (CH2), 42.4 (CH), 40.7 (CH2), 39.2 (CH), 31.8 (CH2),
28.2 (CH), 26.3 (CH2), 25.1 (CH3), 24.4 (CH3), 23.9 (CH2),
22.8 (CH3), 20.0 (CH3), 9.9 (CH3). HRMS: m/z calcd for
C20H32ONa [M + Na]: 311.2351; found: 311.2352.
Crystal Data for Norhydroxynorfusicoauritone (23a)
X-ray data were collected at 110 K on a SMART CCDBRUKER diffractometer with graphite-monochromated Mo
Ka radiation (l = 0.71073 Å). The structure was solved by
direct methods (SIR 92). Refinement was by full-matrix
© Thieme Stuttgart · New York
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126
LETTER
Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone
I > 2s(I) and 0.0762 for all data. wR2 = 0.126, GOF = 1.004,
restrained GOF = 1.004 for all data. An ORTEP diagram is
depicted in Figure 2. Crystallographic data has been
deposited with Cambridge Crystallographic Data Centre
(CCDC 838173).
(11) Found to contain variable amount of the 1,3-transposed
allylic secondary alcohol (similar to 27).
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least-squares procedures on F2 using SHELXL-97. The
nonhydrogen atoms were refined anisotropically whereas
hydrogen atoms were refined isotropically. C19H30O;
MW = 274.43; colorless; crystal system: monoclinic; space
group P21; cell parameters, a = 10.383 (2) Å, b = 6.2198 (6)
Å, c = 13.4758 (19) Å; b = 111.238 (19)°, V = 811.2 (2) Å3,
Z = 2, Dc = 1.124 g cm–3, F(000) = 304, m = 0.067 mm–1.
Total number of l.s. parameters = 2853, R1 = 0.058 for 2290
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© Thieme Stuttgart · New York
Synlett 2012, 23, 123–127