Synthetic studies towards novel terpenic natural products kelsoene and poduran: Construction of the complete 4-5-5-fused tricarbocyclic core

Article abstract of DOI:10.1055/s-1999-2670

A common synthetic approach to the recently reported sesquiterpene kelsoene 1 and the tetraterpene poduran 5, bearing a novel tricyclo[6.2.0.0^2,6]decane framework, from commercially available 1,5-COD and leading to the first construction of the carbocyclic core present in these natural products is delineated.

Full text of DOI:10.1055/s-1999-2670

LETTER
555
Synthetic Studies Towards Novel Terpenic Natural Products Kelsoene and
Poduran: Construction of the Complete 4-5-5-Fused Tricarbocyclic Core
Goverdhan Mehta*, K. Srinivas
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Fax +91 (80) 3341936
Received 18 January 1999
In our synthetic approach to 1 and 5, we identified the tri-
cyclic ketone 6 as the common advanced intermediate in
which the desired side-chain corresponding to the natural
products could be appended. Towards 6, readily available
diquinane dione 86 was chosen as the key building-block.
Dione 8 is accessible in quantity from the commercially
available 1,5-cyclooctadiene 7, Scheme 2.7 Selective
mono-methylenation on 8 through controlled Wittig reac-
tion furnished 9. Catalytic hydrogenation on 9 proceeded
preferentially from the convex face to furnish the endo-
methyl isomer 10 (80:20) along with the minor exo-meth-
yl diastereomer. The trimethylsilylenolether derived from
10 on Pd+2 mediated dehydrogenation8 furnished enone
11, which was further subjected to alkylative enone trans-
position via methyl lithium addition and PCC oxidation to
yield 12.9 The diquinane enone 12 was well poised for the
annulation of a four membered ring through the olefin-
enone [2+2]-photocycloaddition. Irradiation of a mixture
of enone 12 and trans-1,2-dichloroethylene led to the for-
mation of [2+2]-addition product 139 as a mixture of cis-
and trans-1,2- dichloro isomers in good yield. The photo-
cycloaddition in 12 proceeded exclusively from the exo-
face of the diquinane moiety to generate the requisite cis,
anti, cis ring junction stereochemistry in the tricyclic sys-
tem. Direct reductive dehalogenation on 13 presented
considerable difficulties and therefore the carbonyl group
was first protected and further treatment with sodium
naphthalenide furnished the tricyclic cyclobutene deriva-
tive 14, Scheme 2.9 Catalytic hydrogenation and acetal
deprotection led to the desired tricyclic ketone 6. 9
Abstract: A common synthetic approach to the recently reported
sesquiterpene kelsoene 1 and the tetraterpene poduran 5, bearing a
novel tricyclo[6.2.0.02,6]decane framework, from commercially
available 1,5-COD and leading to the first construction of the car-
bocyclic core present in these natural products is delineated.
Key words: sesquiterpen and tetraterpenes, [2+2]-photocycloaddi-
tion, tricyclo [6.2.0.02,6] decane system
In 1997, isolation and structure determination of a novel
sesquiterpene kelsoene 1, from the tropical marine sponge
Cymbastela hooperi collected from Kelso reef, Great Bar-
rier Reef, Australia, was reported.1 More recently, in
1998, the same natural product 1, bearing the new and bio-
genetically interesting tricyclo[6.2.0.02,6]decane frame-
work, was encountered in the cultured cells of liverwort
Ptychanthus straitus.2 Labelling studies2 with [2-13C]-me-
valonate indicated that the uncommon skeleton of 1 is bio-
synthesized from farnesyl pyrophosphate 2 through the
intermediacy of germacradienyl 3 and alloaromadendra-
nyl 4 cations, Scheme 1. Another natural product poduran
5, an unusual tetraterpene bearing the same 4-5-5-fused
tricarbocyclic skeleton as kelsoene 1, has been reported
recently from the springtail Podura aquatica.3 The novel-
ty of the diquinane based carbon framework present in
kelsoene and poduran, with six contiguous stereogenic
centres, immediately attracted our attention. Herein, we
report the first acquisition of the complete 4-5-5-fused tri-
cabocyclic framework4,5 of these natural products with the
desired cis, anti, cis ring fusion of the three rings and fully
secured stereochemistry at the five stereogenic centres.
To elaborate 6 to the target natural products, its reaction
with several nucleophiles and ylides was studied. How-
ever, the carbonyl group in 6 proved to be extremely re-
fractory towards various reagents, indicating the sterically
encumbered environment around it due to the presence of
the C-5 endo- methyl group on one face and the endo-di-
rected cyclobutane hydrogens at C-9 and C-10 on the oth-
er. Efforts are currently underway to overcome these
steric barriers through tactical modifications.
Scheme 1
Synlett 1999, No. 5, 555–556 ISSN 0936-5214 © Thieme Stuttgart · New York

556
G. Mehta, K. Srinivas
LETTER
References and Notes
(1) Konig, G.; Wright, A.D. J. Org. Chem. 1997,62, 3837.
(2) Nabeta, K.; Yamamoto, K.; Hashimoto, M.; Koshino, H.;
Funatsuki, K.; Katoh, K. J. Chem. Soc. Chem. Commun. 1998,
1485.
(3) Schulz, S.; Messer, C.; Dettner, K. Tetrahedron Lett. 1997,
38, 2077.
(4) While the formation of the tricyclo[6.2.0.02,6]decane system
has been recorded before, no compound corresponding to the
skeleton present in 1 and 5 has been reported; see, Ohfune, Y.;
Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1975, 4377;
Mehta, G.; Srikrishna, A. Tetrahedron Lett. 1979, 3187;
Klunder, A.J.H.; Ariaans, G.J.A.; Van de Loop, E.A.R.M.;
Zwanenburg, B. Tetrahedron. 1986, 42, 1903.
(5) For a recent review on the synthesis of diquinane natural
products, see, Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97,
671.
(6) Mehta, G.; Rao, K.V. Ind. J. Chem. 1991, 30B, 457.
(7) Henry, P.M.; Davies, M.; Ferguson,G.; Philips, S.; Restivo, R.
J. Chem. Soc. Chem. Commun. 1974, 112.
(8) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011
(9) All new compounds reported here were duly characterized on
the basis of spectral (IR, 1H and 13C NMR) and analytical data.
Selected spectral data:9:1H NMR (200 MHz, CDCl3): d 4.96
(s, 2H), 3.32-3.04 (br s, 1H) 2. 76- 2.46 (m, 1H), 2.40-1.84
(series of m, 8H); 13C NMR (50.0 MHz, CDCl3): d 222.2,
155.1, 106.3, 52.7, 45.5, 37.3, 32.9, 27.4, 27.0; 12:1H NMR
(300 MHz, CDCl3): d 5.85 (s, 1H) 3.12 (br s, 1H), 2.62 (dd
J1 = 9.9Hz, J2 = 5.7Hz, 1H), 2.11- 2.01 (m, 1H), 2.04 (s, 3H),
1.82- 1.57 (m, 3H), 1.04 (d,J = 6.9Hz, 3H), 1.01- 0.93 (m,
1H); 13C NMR (75.0 MHz, CDCl3): d 210.2, 179.6, 132.4,
53.7, 50.9, 37.0, 32.2, 27.7, 17.4, 15.5; 6:1H NMR (300 MHz,
CDCl3): d 2.95 (t,J = 8.7Hz,1H), 2.39-2.24 (m, 3H), 2.15-
2.13 (m, 1H), 1.93- 1.68 (m, 4H), 1.66- 1.50 (m, 2H), 1.25 (s,
3H), 1.16- 1.05 (m, 1H), 1.01 (d, J = 7.2 Hz, 3H); 13C NMR
(75.0 MHz, CDCl3): d 225.6, 57.9, 52.4, 51.8, 44.2, 37.9, 35.0,
34.1, 27.8, 21.0, 20.9, 16.4.
Scheme 2: Reagents: (a) i. PdCl2, Pb(OAc)4, AcOH, 70%; ii. KOH/
MeOH, 95%; iii. PCC, 85%; (b) MePPh3I,K+-OtBu, 65%; (c) H2, 10%
Pd/C, EtOAc, 90%; (d) i. LHMDS, TMSCl, ii. Pd(OAc)2, MeCN,
80%;(e) i.MeLi, Et2O, ii. PCC, 80%; (f) trans-1,2-dichloro-ethylene,
C6H12, hn, pyrex, 85%; (g) i. (CH2OH)2, PTSA, benzene, 85%; ii. so-
dium napthalenide, DME, 95%; (h) i. H2, 10% Pd/C, EtOAc, 95%; ii.
Amberlyst-15, acetone, 85%
In summary, we have outlined a simple synthesis of the
tricyclo[6.2.0.02,6]decane based carbocyclic framework 6
present in the recently reported sesquiterpene kelsoene 1
and tetraterpene poduran 5, from readily available 1,5-
COD
Article Identifier:
1437-2096,E;1999,0,05,0555,0556,ftx,en;L02099ST.pdf
Acknowledgement
We thank UGC for a research fellowship to K.S.
Synlett 1999, No. 5, 555–556 ISSN 0936-5214 © Thieme Stuttgart · New York