2652
LETTER
An Enantiospecific Approach to Tetraquinane Diterpenes Crinipellins:
Synthesis of Norcrinipellins
Synthesi ofNorcinpelins Srikrishna,* V. Gowri
A.
Abstract: An enantiospecific approach to the synthesis of tetraquinane diterpene crinipellins is described. The cyclopentane ring
in campholenaldehyde was identified as the B ring. Two rhodium
carbenoid CH insertion reactions for the construction of A and C
rings and an intramolecular Michael addition reaction for the D ring
of crinipellins were employed as key strategies for the enantiospecific synthesis of norcrinipellins.
Key words: crinipellins, tetraquinanes, enantiospecific synthesis,
campholenaldehyde, intramolecular Michael addition
In 1979, the research groups of Anke and Steglich
reported1 the isolation of an antibiotic with undetermined
structure, named crinipellin 1 (later modified to O-acetylcrinipellin A) from the submerged cultures of basidomycete Crinipellis stipitaria, strain 7612, which was
found to be most active against Gram-positive bacteria
(Figure 1). Subsequently, further investigations by
Steglich and co-workers2 on several strains of C. stipitaria
led to the isolation of several related crinipellins 2–5, of
which 2 and 3 were found to exhibit antibiotic activity,
whereas 4 and 5 were found to be inactive. Structure elucidation by spectroscopic methods of compounds 1–5 revealed a new diterpene skeleton containing a tetraquinane
carbon framework (tetracyclo[6.6.0.01,11.03,7]tetradecane;
6), which was confirmed by single crystal X-ray diffraction analysis of crinipellin B (3). The absolute configurations of crinipellins 1–5 were assigned by comparing the
CD curves with those of linear triquinane sesquiterpene
hypnophilin and ent-3b-hydroxy-5a-androstan-17-one,
and are yet to be confirmed. The crinipellins are the first
group of natural products to contain a tetraquinane framework that incorporates both a linear cis,anti,cis-triquinane
(ABC-rings) as well as an angular triquinane (BCD-rings)
system (both are present separately in a number of sesquiterpenes) as integral parts.3 Recently, Shen and Li
reported4 the isolation of four more crinipellins 7–10 from
the fungal strain Crinipellis sp. 113. Although these latter
compounds had no effect on the growth of the bacteria or
yeast, they exhibited moderate antitumor activity against
HeLa cells.
The interesting tetraquinane framework comprising a linear cis,anti,cis-triquinane as well as an angular triquinane
system, the presence of three contiguous all carbon qua-
ternary carbon atoms, and eight to ten stereogenic centres,
coupled with the potential biological activity, makes the
crinipellin group of diterpenes an interesting synthetic target. Subsequent to the first report by the research group of
Mehta on the synthesis of the complete carbon framework
of 12-epicrinipellin in racemic form (the ABC→ABCD
approach),5 Piers et al. reported6 the first total synthesis of
racemic crinipellin-B (3) employing a D→CD→BCD→ABCD ring construction approach. Later, Wender
et al. accomplished7 a formal total synthesis of crinipellin
B (3), by employing an intramolecular olefin meta-photocycloaddition based strategy for the synthesis of an angular triquinane (BCD), which was an advanced
intermediate in the synthesis developed by Piers et al.
So far, to the best of our knowledge, there is no report in
the literature on the enantioselective generation (neither
total synthesis nor model studies) of any crinipellin. Recently, in a continuation of our interest in the chiral pool
based enantiospecific synthesis of natural products starting from readily available (S)-campholenaldehyde 11,8
we have reported an enantiospecific synthesis of the linear
cis,anti,cis-triquinane 12 starting from 11,8a which
H
H
R1
OR
O
O
1 R = Ac
2 R = H (crinipellin A)
O
OH
3 R1,R2 = O (crinipellin B)
1 = OH; R2 = H
4R
H
H
OH
HO
5
OH
HO
O
O
O
2
R1 R
7 R1,R2 = O
8 R1 = H; R2 =OH;
H
H
HO
O
HO
O
O
9 (crinipellin C)
5
O
10 (crinipellin D)
D
A
B
11
1
C
7
6
Figure 1
OH
HO
O
3
SYNLETT 2011, No. 18, pp 2652–2656xx. 201
Advanced online publication: 19.10.2011
DOI: 10.1055/s-0031-1289533; Art ID: D21011ST
© Georg Thieme Verlag Stuttgart · New York
O
R2
O
9
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 4 July 2011
LETTER
2653
Synthesis of Norcrinipellins
prompted us to investigate the enantiospecific synthesis of
the tetraquinane framework of crinipellins 1–5 and 7–10.
Herein, we report an enantiospecific strategy to access
norcrinipellins.
It was contemplated (Scheme 1) that the cyclopentane
ring in (S)-campholenaldehyde 11 would serve as the Bring of crinipellins, and that the D-ring of crinipellins
could be realized through an intramolecular Michael addition of an ester onto an enone in the C-ring, for example
13. Synthesis of the enone ester 13 was anticipated to be
achieved from the b-keto ester 12 via the triquinane enone
14. Synthesis of the b-keto ester 12 from (S)-campholenaldehyde 11 has already been developed in our laboratory
by employing two rhodium carbenoid CH insertion
reactions9 for the construction of the A and C rings.8a,b
lithium chloride in dimethyl sulfoxide (DMSO) and water
at 180 °C generated enone 19 in 71% yield.12 To generate
a suitable side chain for annulation of the D-ring, first an
allyl moiety was introduced at the C-6 carbon of enone 19.
Thus, reaction of 19 with lithium diisopropylamide
(LDA), followed by treatment of the resultant dienolate
with allyl bromide generated triquinane 21 in 82% yield in
a highly stereoselective manner by approach of the electrophile from the less hindered exo face of the BC-ring
system, which also resulted in the formation of the thermodynamically preferred cis ring junction of the B and C
rings.
R
H
a
O
OHC
15
OMe
ROOC
H
17
11 R = H
16 R = CHN2
H
b
D
B
C
OMe
A
H
norcrinipellin
O
H
O
Me H
O 13
H
R
ROOC
c
OMe
O
74%
H
Y
H
R
15
CHO
H
11
Scheme 1
The synthetic sequence is depicted in Scheme 2 and
Scheme 3. To begin with, the synthesis of the key intermediate of the sequence, triquinane 12, was carried out by
employing the methodology developed earlier.8a
Diquinane 15 was obtained8b through regiospecific CH insertion reaction of the rhodium carbenoid derived from diazoketone 16. Diquinane 15 was then transformed into
aldehyde 17, which was converted into the a-diazo-b-keto
ester 18 in four steps, invovling hydrogenation, equilibration of the aldehyde to the exo orientation, coupling of the
aldehyde with methyl diazoacetate, and diazo transfer reaction. Regiospecific insertion of the rhodium carbenoid
derived from the diazo ester 18 into the cis methyl group
furnished the key intermediate triquinane 12 in a highly
regioselective manner. For generating a suitable Michael
donor in the C-ring, the b-keto ester 12 was transformed
into enone 19. Thus, reaction of ester 12 with phenylselenyl chloride in the presence of pyridine, followed by oxidation of the selenide with hydrogen peroxide generated
the unsaturated b-keto ester 20 in 74% yield. Krapcho’s
dealkoxycarbonylation reaction10 of keto ester 20 with
82%
OMe
Me H
H
20 R = COOMe
19 R = H
H
X
e
H
H
18
MeOOC
12
Me H
O
14
O
OMe
N2
OMe
Me H
H
OMe
Me H
12
H
O
b
MeOOC
H
H
OMe
Me H
21 X,Y = O
22 X = Me, Y = OH
d 71%
f 92%
g 90%
MeOOC
H
Me
X
Me
i
93%
OMe
Me H
H
OMe
Me H
O
23 X = H2 h 88%
24 X = O
O
25
j 100%
(10:1)
MeOOC
MeOOC
H
Me
k
H
Me
78%
Me H
OMe
O
26
Me H
OMe
O
27n
Scheme 2 Reagents and conditions: (a) ref. 8b; (b) ref. 8a; (c) (i)
PhSeCl, py, CH2Cl2, 0 °C, 1 h; (ii) 30% H2O2, CH2Cl2, 0 °C, 0.5 h; (d)
LiCl, DMSO, H2O, 180 °C, 10 h; (e) LDA, THF; CH2=CHCH2Br,
–70 °C→r.t., 7 h; (f) MeLi, THF, Et2O, 0 °C→r.t., 10 h; (g) PCC, silica gel, CH2Cl2, r.t., 1 h; (h) O3/O2, CH2Cl2–MeOH (4:1), –70 °C;
Me2S, r.t., 3 h; (i) (EtO)2P(O)CH2CO2Et, NaH, THF, 0 °C→r.t. 8 h;
(j) H2 (1 atm), (Ph3P)3RhCl, EtOAc, r.t., 24 h; (k) LDA, THF, –70 °C
→r.t., 6 h.
Prior to the elaboration of the allyl group into a suitable
Michael donor, the enone moiety in the C-ring of 21 was
modified into a Michael acceptor with the electrophilic
Synlett 2011, No. 18, 2652–2656
© Thieme Stuttgart · New York
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H
LETTER
A. Srikrishna, V. Gowri
site at the C-5 carbon atom. Because a methyl group needs
to be present on the C-11 carbon of crinipellins, an alkylative 1,3-enone transposition methodology11 was adopted. Stereo- and regioselective 1,2-addition of
methyllithium to enone 21, followed by oxidation of the
resultant allylic tertiary alcohol 22 with pyridinium chlorochromate (PCC) and silica gel in methylene chloride
furnished the 1,3-transposed enone 23 in 90% yield.12 A
three-step strategy was employed for the conversion of the
allyl group into a butanoate side chain in enone 23. Thus,
controlled ozonolysis of the olefin of the allyl group in 23,
followed by reductive workup with dimethyl sulfide, generated aldehyde 24 in a highly regioselective manner.
Horner–Wadsworth–Emmons reaction with sodium hydride and triethyl phosphonoacetate furnished unsaturated
ester 25 in 93% yield.12 Hydrogenation of the unsaturated
ester with Wilkinson’s catalyst furnished the dihydro derivative 26 in a highly regioselective manner.
HO
HO
H
H
Me
Me
OMe
Me H
O
O
+ Me
27n
86%
(10:1)
b 84%
H
MeOOC
a
27n + 27x
(4:5)
c
Me H
O
69%
Me
MeO
In another direction, the esters 27x and 27n were transformed into the acetyl compounds 29x and 29n via the
corresponding Weinreb amides 30x and 30n. Wittig reaction of diones 29x and 29n with methylenetriphenylphosphorane generated norcrinipellin 31x and 12epinorcrinipellin 31n in a highly regioselective manner,12
because of the steric crowding of C-9 ketone. In order to
establish the stereochemistry at all the stereocenters, norcrinipellin 28x was subjected to single crystal X-ray diffraction analysis;12 an ORTEP diagram is depicted in
Figure 2 that confirms the stereostructure.
28x
28n
b 87%
OMe
Me H
cation will interact with both the enolate and enone oxygen atoms in the transition state during the intramolecular
Michael addition reaction. Because the isopropyl side
chain in crinipellins is oriented exo to the CD-ring system,
ester 27 was equilibrated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to furnish a 4:5 mixture of 27n and 27x,
which were separated by column chromatography on alumina. Finally, esters 27x and 27n were transformed into
norcrinipellin 28x and 12-epinorcrinipellin 28n, respectively,12 in a highly regioselective manner by treatment
with an excess of methylmagnesium chloride and exploiting the steric crowding of the C-9 ketone group in 27.
N
MeO
OMe
27x
c 79%
Me
N
H
O
H
O
Me
Me
Me H
OMe
OMe
Me H
O
O
30n
b 92%
b 95%
H
X
Figure 2
H
X
Me
Me
Me H
OMe
O
29n X =O
d 76%
31n X = CH2
Me H
O
29x X =O
31x X = CH2
OMe
d 71%
Scheme 3 Reagents and conditions: (a) DBU, benzene, sealed tube,
180 °C, 24 h; (b) 3M MeMgCl, Et2O, 0 °C→r.t., 3 h; (c)
MeN(OMe)MgCl, THF, –30 °C, 1 h; (d) Ph3P+CH3Br–, t-AmO–K+,
benzene, r.t., 0.5 h.
Generation of the enolate of the enone ester 26 with LDA
led to the intramolecular Michael addition generating a
10:1 C-12 epimeric mixture of tetraquinane esters 27n and
27x in 78% yield. Generation of the cis ring junction of
the C and D rings was clear because the Michael addition
was possible only through a syn approach. The stereochemistry of the ester group in the major isomer 27n was
assigned as endo based on the assumption that the lithium
Synlett 2011, No. 18, 2652–2656
ORTEP diagram of norcrinipellin 28x
30x
© Thieme Stuttgart · New York
In conclusion, we have developed an enantiospecific approach to the tetraquinane ring system of crinipellin diterpenes, starting from (S)-campholenaldehyde 11. The
cyclopentane ring in 11 was identified as the B-ring, and
two intramolecular rhodium carbenoid CH-insertion reactions were exploited for the formation of the A and Crings. An intramolecular Michael addition reaction was
employed for the construction of the D-ring of crinipellins. The structure of the norcrinipellin 28x was confirmed
by single crystal X-ray diffraction analysis. Extension of
the strategy for the enantiospecific synthesis of natural
crinipellins and their analogues is in progress.
Acknowledgment
We thank the CCD Facility, Indian Institute of Science, for the Xray diffraction analysis, and the CSIR, New Delhi for the award of
a Research Fellowship to V.G. We are grateful to Organica Aromatics (Bangalore) Pvt. Ltd. for the generous gift of campholenaldehyde.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
2654
References
(1) Kupka, J.; Anke, T.; Oberwinkler, F.; Schramm, G.;
Steglich, W. J. Antibiot. 1979, 32, 130.
(2) Anke, T.; Heim, J.; Knoch, F.; Mocek, U.; Steffan, B.;
Steglich, W. Angew. Chem., Int. Ed. Engl. 1985, 24, 709.
(3) (a) Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97, 671.
(b) Singh, V.; Thomas, B. Tetrahedron 1998, 54, 3647.
(4) Li, Y.-Y.; Shen, Y.-M. Helv. Chim. Acta 2010, 93, 2151.
(5) Mehta, G.; Rao, K. S.; Reddy, M. S. J. Chem. Soc., Perkin
Trans. 1 1991, 693.
(6) Piers, E.; Renaud, J.; Rettig, S. J. Synthesis 1998, 590.
(7) Wender, P. A.; Dore, T. M. Tetrahedron Lett. 1998, 39,
8589.
(8) (a) Srikrishna, A.; Gowri, V.; Neetu, G. Tetrahedron:
Asymmetry 2010, 21, 202. (b) Srikrishna, A.; Beeraiah, B.;
Satyanarayana, G. Tetrahedron: Asymmetry 2006, 17, 1544.
(c) Srikrishna, A.; Beeraiah, B. Tetrahedron: Asymmetry
2007, 18, 2587. (d) Srikrishna, A.; Beeraiah, B.; Babu, R. R.
Tetrahedron: Asymmetry 2008, 19, 624. (e) Srikrishna, A.;
Beeraiah, B. Tetrahedron: Asymmetry 2008, 19, 884.
(f) Srikrishna, A.; Beeraiah, B.; Gowri, V. Tetrahedron
2009, 65, 2649. (g) Srikrishna, A.; Neetu, G. Tetrahedron:
Asymmetry 2010, 21, 2067.
(9) (a) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091.
(b) Doyle, M. P. In Comprehensive Organometallic
Chemistry II, Vol. 12; Hegedus, L. S., Ed.; Pergamon Press:
New York, 1995, Chap. 5.2. (c) Doyle, M. P.; McKervey,
M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds: from Cyclopropanes to
Ylides; John Wiley and Sons: New York, 1998, Chap. 3.
(10) Krapcho, A. P. Synthesis 1982, 893.
(11) (a) Büchi, G.; Egger, B. J. Org. Chem. 1971, 36, 2021.
(b) Srikrishna, A.; Sharma, G. V. R.; Danieldoss, S.;
Hemamalini, P. J. Chem. Soc., Perkin Trans. 1 1996, 1305.
(12) Yields refer to isolated and chromatographically pure
compounds. All the compounds exhibited spectroscopic data
(IR, 1H and 13C NMR and HRMS) consistent with their
structures. Spectroscopic data for (1R,2S,6R,8S,10R)-10methoxy-2-methyltricyclo[6.3.0.02,6]undec-3-en-5-one (19):
[a]D21 –76.8 (c 4.6, CHCl3); IR (neat): 1710, 1589, 1366,
1342, 1265, 1185, 1110, 1004, 836, 817, 784 cm–1; 1H NMR
(300 MHz, CDCl3): d = 7.39 (d, J = 5.4 Hz, 1 H, H-3), 6.02
(d, J = 5.4 Hz, 1 H, H-4), 3.83 (tt, J = 8.7, 6.3 Hz, 1 H, H10), 3.28 (s, 3 H, OCH3), 2.36 (dd, J = 9.9, 1.5 Hz, 1 H, H6), 2.25–1.90 (m, 6 H), 1.59 (dd, J = 11.4, 8.1 Hz, 1 H), 1.46
(dd, J = 13.5, 5.1 Hz, 1 H), 1.29 (s, 3 H, tert-CH3); 13C NMR
(100 MHz, CDCl3): d = 212.8 (C, C=O), 172.0 (CH, C-3),
131.3 (CH, C-4), 83.7 (CH, C-10), 58.0 (CH, C-6), 57.0
(CH3, OCH3), 55.1 (C, C-2), 49.5 (CH, C-1), 40.9 (CH, C-8),
37.0 (CH2), 36.1 (CH2), 33.5 (CH2), 21.5 (CH3, tert-CH3);
HRMS: m/z calcd for C13H18O2Na [M + Na]: 229.1205;
found: 229.1208.
(1R,2S,6S,8S,10R)-6-Allyl-10-methoxy-2,5-dimethyltricyclo[6.3.0.02,6]undec-4-en-3-one (23): [a]D25 –29.8
(c 3.5, CHCl3); IR (neat): 1701, 1622, 1374, 1285, 1111,
995, 915, 865 cm–1; 1H NMR (300 MHz, CDCl3): d = 5.91
(s, 1 H, H-4), 5.60 (ddt, J = 16.8, 9.9, 7.2 Hz, 1 H, CH=CH2),
5.06 (dd, J = 16.7, 1.8 Hz, 1 H, CH=CH2), 5.01 (dd, J = 9.9,
1.8 Hz, 1 H, CH=CH2), 3.78 (tt, J = 8.4, 5.7 Hz, 1 H, H-10),
3.28 (s, 3 H, OCH3), 2.50–2.37 (m, 2 H), 2.26 (dt, J = 12.0,
7.5 Hz, 1 H), 2.15–1.85 (m, 4 H), 2.02 (s, 3 H, olefinic CH3),
1.69–1.55 (m, 1 H), 1.49 (dd, J = 15.3, 8.4 Hz, 1 H), 1.41
(dd, J = 15.3, 4.5 Hz, 1 H), 1.09 (s, 3 H, tert-CH3); 13C NMR
(100 MHz, CDCl3): d = 212.9 (C, C=O), 180.4 (C, C-5),
134.6 (CH, CH=CH2), 130.2 (CH, C-4), 117.6 (CH2,
CH=CH2), 83.2 (CH, C-10), 61.6 (C, C-2), 59.0 (C, C-6),
57.0 (CH3, OCH3), 51.1 (CH, C-1), 41.7 (CH2), 39.0 (CH2),
Synthesis of Norcrinipellins
2655
37.8 (CH, C-8), 35.7 (CH2), 33.5 (CH2), 15.6 (CH3), 15.4
(CH3); HRMS: m/z calcd for C17H24O2Na [M + Na]:
283.1674; found: 283.1662.
Ethyl 4-[(1R,2S,6S,8S,10R)-10-methoxy-2,5-dimethyl-3oxotricyclo[6.3.0.02,6]undec-4-en-6-yl]but-2-enoate (25):
[a]D20 –60.6 (c 3.3, CHCl3); IR (neat): 1713, 1704, 1652,
1622, 1460, 1442, 1370, 1269, 1219, 1184, 1099, 1039, 977,
867 cm–1; 1H NMR (400 MHz, CDCl3): d = 6.67 (dt, J =
15.6, 7.9 Hz, 1 H, H-3), 5.89 (s, 1 H, H-4¢), 5.78 (d, J =
15.6 Hz, 1 H, H-2), 4.09 (q, J = 7.1 Hz, 2 H, OCH2CH3),
3.80–3.65 (m, 1 H, H-10¢), 3.21 (s, 3 H, OCH3), 2.52 (dd,
J = 15.8, 6.5 Hz, 1 H, H-4), 2.45 (dd, J 15.7, 8.2 Hz, 1 H, H4), 2.27–2.20 (m, 2 H), 2.15–1.75 (m, 3 H), 1.96 (s, 3 H,
olefinic-CH3), 1.61 (t, J = 12.4 Hz, 1 H), 1.47–1.34 (m, 2 H),
1.21 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.01 (s, 3 H, tert-CH3);
13
C NMR (100 MHz, CDCl3): d = 212.3 (C, C=O), 179.2 (C,
C-5¢), 165.6 (C, OC=O), 144.6 (CH, C-3), 130.7 (CH, C-4¢),
123.9 (CH, C-2), 83.1 (CH, C-10¢), 61.3 (C, C-2¢), 60.2
(CH2, OCH2CH3), 59.3 (C, C-6¢), 57.0 (CH3, OCH3), 51.1
(CH, C-1¢), 41.6 (CH2), 37.9 (CH, C-8¢), 37.6 (CH2), 35.6
(CH2), 33.6 (CH2), 15.9 (CH3), 15.5 (CH3), 14.2 (CH3);
HRMS: m/z calcd for C20H28O4Na [M + Na]: 355.1886;
found: 355.1894.
2-[(1S,3S,5R,7R,8S,11S,12R)-5-Methoxy-8,11-dimethyl-9oxotetracyclo[6.6.0.01,11.03,7]tetradecan-12-yl]propan-2-ol
(28x, norcrinipellin): m.p. 118–119 °C; [a]D24 –64.6 (c 1.4,
CHCl3); IR (KBr): 3473 (OH), 2959, 2880, 1731 (C=O),
1460, 1373, 1225, 1108, 949 cm–1; 1H NMR (400 MHz,
CDCl3): d = 3.77 (tt, J = 8.4, 6.4 Hz, 1 H, H-5), 3.29 (s, 3 H,
OCH3), 2.75 (d, J = 17.8 Hz, 1 H, H-10A), 2.37–2.15 (m,
2 H), 2.14 (d, J = 17.8 Hz, 1 H, H-10B), 2.15–1.90 (m, 4 H),
1.86–1.30 (m, 8 H), 1.32 (s, 3 H, tert-CH3), 1.22 (s, 3 H, tertCH3), 1.20 (s, 3 H, tert-CH3), 1.12 (s, 3 H, tert-CH3); 13C
NMR (100 MHz, CDCl3): d = 224.4 (C, C=O), 82.9 (CH, C5), 72.9 (C, C-OH), 65.9 (C, C-1), 60.8 (C, C-8), 57.3 (CH3,
OCH3), 57.2 (CH, C-12), 53.6 (CH, C-7), 52.0 (CH2), 49.4
(C, C-11), 43.5 (CH2), 39.5 (CH, C-3), 37.1 (CH2), 34.3
(CH2), 33.0 (CH2), 31.3 (CH3) and 30.2 (CH3) [2 × tertCH3], 25.0 (CH2), 18.9 (CH3) and 17.8 (CH3) [2 × tert-CH3];
HRMS: m/z calcd for C20H32O3Na [M + Na]: 343.2250;
found: 343.2238; Anal. Calcd. for C20H32O3: C, 74.96; H,
10.06. Found: C, 74.95; H, 10.17.
2-[(1S,3S,5R,7R,8S,11S,12S)-5-Methoxy-8,11-dimethyl-9oxotetracyclo[6.6.0.01,11.03,7]tetradecan-12-yl]propan-2-ol
(28n, 12-epinorcrinipellin): [a]D23 +4.0 (c 1.0, CHCl3); IR
(neat): 3469, 1729, 1371, 1257, 1220, 1113, 942 cm–1; 1H
NMR (400 MHz, CDCl3): d = 3.77 (quint., J = 7.3 Hz, 1 H,
H-5), 3.28 (s, 3 H, OCH3), 3.19 (d, J = 17.0 Hz, 1 H, H10A), 2.48 (dt, J = 12.0, 7.6 Hz, 1 H), 2.26 (dd, J = 13.8,
6.8 Hz, 1 H), 2.20–2.04 (m, 2 H), 2.00 (d, J = 17.0 Hz, 1 H,
H-10B), 2.05–1.90 (m, 2 H), 1.80–1.65 (m, 2 H), 1.64 (dd,
J = 10.9, 6.3 Hz, 1 H), 1.55–1.35 (m, 5 H), 1.32 (s, 3 H, tertCH3), 1.24 (s, 3 H, tert-CH3), 1.21 (s, 3 H, tert-CH3), 1.02 (s,
3 H, tert-CH3); 13C NMR (100 MHz, CDCl3): d = 222.6 (C,
C=O), 83.5 (CH, C-5), 72.6 (C, C-OH), 65.4 (C, C-1), 59.1
(CH, C-12), 59.0 (C, C-8), 57.1 (CH3, OCH3), 50.3 (CH, C7), 47.1 (C, C-11), 46.8 (CH2), 45.7 (CH2), 40.0 (CH, C-3),
37.3 (CH2), 34.9 (CH2), 33.6 (CH2), 31.7 (CH3), 30.8 (CH3),
27.2 (CH2), 27.1 (CH3), 17.2 (CH3); HRMS: m/z calcd for
C20H32O3Na [M + Na]: 343.2250; found: 343.2241.
(1S,3S,5R,7R,8S,11S,12S)-12-Isopropenyl-5-methoxy-8,11dimethyltetracyclo[6.6.0.01,11.03,7]tetradecan-9-one (31x):
[a]D22 –22.5 (c 0.4, CHCl3); IR (neat): 1733, 1637, 1376,
1257, 1223, 1192, 1117, 891 cm–1; 1H NMR (400 MHz,
CDCl3): d = 4.86 (s, 1 H, C=CH2), 4.68 (s, 1 H, C=CH2),
3.77 (quint., J = 7.0 Hz, 1 H, H-5), 3.29 (s, 3 H, OCH3), 2.56
(d, J = 17.8 Hz, 1 H, H-10A), 2.34–2.25 (m, 2 H), 2.17–1.75
Synlett 2011, No. 18, 2652–2656
© Thieme Stuttgart · New York
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LETTER
A. Srikrishna, V. Gowri
(m, 6 H), 1.73 (s, 3 H, olefinic CH3), 1.74–1.60 (m, 3 H),
1.51–1.40 (m, 2 H), 1.31 (dd, J = 11.0, 6.8 Hz, 1 H), 1.10 (s,
3 H, tert-CH3), 0.93 (s, 3 H, tert-CH3); 13C NMR (100 MHz,
CDCl3): d = 223.6 (C, C=O), 144.3 (C, C=CH2), 113.3 (CH2,
C=CH2), 83.0 (CH, C-5), 64.7 (C, C-1), 61.2 (C, C-8), 57.2
(CH3, OCH3), 56.3 (CH, C-12), 52.9 (CH, C-7), 50.5 (CH2,
C-10), 49.5 (C, C-11), 44.6 (CH2), 39.7 (CH, C-3), 37.1
(CH2), 34.1 (CH2), 33.7 (CH2), 27.4 (CH2), 23.4 (CH3), 18.3
(CH3), 18.1 (CH3); HRMS: m/z calcd for C20H30O2Na [M +
Na]: 325.2145; found: 325.2139.
(1S,3S,5R,7R,8S,11S,12R)-12-Isopropenyl-5-methoxy8,11-dimethyltetracyclo[6.6.0.01,11.03,7]tetradecan-9-one
(31n): [a]D24 –60.0 (c 0.6, CHCl3); IR (neat): 1732, 1637,
1377, 1261, 1223, 1191, 1115, 1019, 891, 801 cm–1; 1H
NMR (400 MHz, CDCl3): d = 4.86 (s, 1 H, C=CH2), 4.69 (s,
1 H, C=CH2], 3.77 (quint., J = 7.3 Hz, 1 H, H-5), 3.28 (s,
3 H, OCH3), 2.55–2.40 (m, 1 H), 2.45 (d, J = 17.1 Hz, 1 H,
H-10A), 2.17–2.00 (m, 4 H), 2.00–1.88 (m, 2 H), 1.87 (d,
J = 17.1 Hz, 1 H, H-10B), 1.74 (s, 3 H, olefinic CH3), 1.66–
1.60 (m, 1 H), 1.53–1.40 (m, 4 H), 1.31 (dd, J = 11.0, 6.8 Hz,
1 H), 1.18 (s, 3 H, tert-CH3), 1.02 (s, 3 H, tert-CH3]; 13C
NMR (100 MHz, CDCl3): d = 221.7 (C, C=O), 144.8 (C,
C=CH2), 112.9 (CH2, C=CH2), 83.6 (CH, C-5), 64.2 (C, C1), 59.6 (C, C-8), 57.3 (CH3, OCH3), 57.1 (CH, C-12), 50.6
Synlett 2011, No. 18, 2652–2656
© Thieme Stuttgart · New York
LETTER
(CH, C-7), 47.3 (C, C-11), 46.4 (CH2, C-10), 45.7 (CH2),
40.1 (CH, C-3), 37.2 (CH2), 34.8 (CH2), 33.5 (CH2), 29.5
(CH2), 25.1 (CH3), 23.9 (CH3), 16.9 (CH3); HRMS: m/z
calcd for C20H30O2Na [M + Na]: 325.2145; found: 325.2140.
Crystal data for norcrinipellin (28x): X-ray data were
collected at 296 K with a SMART CCDBRUKER
diffractometer with graphite-monochromated MoKa
radiation (0.71073 Å). The structure was solved by direct
methods (SIR 92). Refinement was by full-matrix leastsquares procedures on F2 using SHELXL-97. The
nonhydrogen atoms were refined anisotropically, whereas
hydrogen atoms were refined isotropically. Molecular
formula C20H32O3; MW = 320.5; T = 296 (2) K; Crystal
system: monoclinic; Space group: P21; cell parameters:
a = 9.5828 (4) Å; b = 8.1659 (4) Å; c = 11.7728 (5) Å;
a = 90 (0)°; b = 101.3 (3)°; g = 90 (0)°; V = 903.6 (7) Å3;
Z = 2; Dcalcd = 1.18 g·cm–3; F(000) = 352; m = 0.077 mm–1;
Total number of l.s. parameters = 212; R: = 0.068 for 1789
[I > 2s(I)]; wR2 = 0.216 and 0.0961 for all 12211 data;
GOF = 1.019; Restrained GOF = 1.019 for all data; An
ORTEP diagram is depicted in Figure 2. Crystallographic
data have been deposited with the Cambridge
Crystallographic Data Centre (CCDC 831696).
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