Enantiospecific synthesis of [7R,6S,5S,4R]-triacetoxy-(-)-goniotriol

Article abstract of DOI:10.1016/S0040-4039(02)01048-1

A short and efficient synthesis of [7R,6S,5S,4R]-triacetoxy-(-)-goniotriol starting form D-glucose is described. A sequence of ring closing metathesis (RCM) followed by a PCC oxidation was used to construct the core six-membered α,β-unsaturated lactone mo

Full text of DOI:10.1016/S0040-4039(02)01048-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5471–5473
Enantiospecific synthesis of
[7R,6S,5S,4R]-triacetoxy-(−)-goniotriol
G. S. C. Srikanth, Urlam Murali Krishna and Girish K. Trivedi*
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Received 11 April 2002; revised 24 May 2002; accepted 31 May 2002
Abstract—A short and efficient synthesis of [7R,6S,5S,4R]-triacetoxy-(−)-goniotriol starting form
D-glucose is described. A
sequence of ring closing metathesis (RCM) followed by a PCC oxidation was used to construct the core six-membered
a,b-unsaturated lactone moiety. © 2002 Elsevier Science Ltd. All rights reserved.
Styryllactones, isolated from the stem bark of Gonio-
thalamus giganteus (Annanoceae) have interesting hete-
rocyclic skeletons.1 They show significant murine
toxicity to lymphocytic leukemia systems. The isolation
of further styryllactones, their structure elucidation and
cytotoxic studies are active areas of interest.2,3
Goniotriol, an important member of this family, which
showed significant cytotoxicity in the potato disc test
and the brine shrimp test, is known to occur in both
enantiomeric forms.4 Syntheses of naturally occurring
[7R,6R,5R,4S]-(+)-goniotriol5–8 and its analogues have
been reported and their bioactivities were studied. Fur-
thermore, biomimetic syntheses of other styryllactones
from goniotriol have been reported.6 Owing to its bio-
logical importance, especially its cytoxicity to
lymphocytic leukemia, and the fact that goniotriol
could be further converted to other styryllactones, it
appeared of interest to synthesize various diastereomers
of goniotriol. The synthesis of [7R,6S,5S,4R]-triace-
Results and discussion
The retrosynthetic analysis of our approach is shown in
Scheme 1. It was envisioned that goniotriol 1 could be
synthesized from a RCM product of the dialkenyl ether
2 followed by a PCC oxidation reaction. Furthermore,
2 could originate from the acetonide 3 by incorporating
the required phenyl group in a stereocontrolled step.
The acetonide 3 can be synthesized from
D
-glucose9 by
known steps.
The synthesis commenced with the dialkenyl acetonide
3, which was subjected to hydrolysis using acetic acid in
water at 90°C to furnish an inseparable mixture of
anomeric diols 4 in 86% yield. The anomeric mixture of
diols was subjected to a Grignard reaction with phenyl-
magnesium bromide resulting in an inseparable mixture
of diastereomeric triols 5a and b in a 3:1 ratio. The
stereochemistry of the major isomer was deduced to be
5a by literature analogy9 and was later corroborated by
the single crystal X-ray structure of 1, which was
derived from isomer 5a. The diastereomeric triols 5a
toxy-(−)-goniotriol 1,
a
diastereomer of natural
goniotriol and the enantiomer of 7-epi-goniotriol is
reported here.
O
OAc O
OAc O
O
D-Glucose
O
C6H5
C6H5
AllylO
O
OAc OAc
OAc OAc
3
2
1
Scheme 1.
Keywords: styryllactones; goniotriol; ring closing metathesis; PCC oxidation.
* Corresponding author. E-mail: chgktia@chem.iitb.ac.in
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01048-1

5472
G. S. C. Srikanth et al. / Tetrahedron Letters 43 (2002) 5471–5473
and b on acetylation followed by column chromatogra-
phy afforded essentially pure triacetate 2 in 49% yield
(Scheme 2).
The present synthesis of [7R,6S,5S,4R]-triacetoxy-(−)-
goniotriol from -glucose has demonstrated the utility
of allyl ethers in constructing six-membered a,b-unsatu-
rated lactone moieties through sequential RCM and
PCC oxidation reactions. Further adoption of this
strategy in syntheses of other diastereomers of the title
compound is in progress.
D
The triacetate 2 on subjection to a ring closing metathe-
sis reaction10 using Grubb’s catalyst [benzylidine-bis(tri-
cyclohexylphospine)-dichlororuthenium (5 mol%)] in
dry DCM yielded the cyclic allyl ether 6 in a 90% yield.
The allylic methylene moiety in ether 6 was oxidized
using the conditions reported by Bonadies et al.11
Treatment of the cyclic allyl ether with 3 equiv. of PCC
and pyridine in dry DCM furnished the required styryl-
lactone, [7R,6S,5S,4R]-triacetoxy-(−)-goniotriol in an
overall 12% yield (Scheme 3). As mentioned earlier the
configuration at C-7 derived through the Grignard
reaction on the anomeric diol 4 was based on a litera-
ture analogy,9 which could be ascertained unambigu-
ously from the single crystal X-ray analysis12 (see Fig.
1).
Syntheses of natural products containing six-membered
a,b-unsaturated lactones as a core feature using RCM
reactions have been reported13,14 earlier. These were
achieved through intramolecular RCM reactions of
appropriately substituted acrylyl alkenylic esters. In the
present synthesis we have utilized an allyl ether as a
masked acrylic ester moiety to minimize the protection
and deprotection steps. Since allyl ethers are known to
withstand harsher reaction conditions (both acidic and
basic), the present methodology offers an attractive
alternative to acrylyl ester derived syntheses of cyclic
lactones of various ring sizes.
Figure 1. X-Ray crystal structure of 1.
O
O
a
b
OH
OH
O
D-Glucose
AllylO
AllylO
O
3
4
OAc O
R2 O
R1
C6H5
d
c
C6H5
OAc OAc
OH OH
5 (a) R1 = OH R2 = H
(b) R1 = H R2 = OH
2
Scheme 2. Reaction conditions: (a) four steps (Ref. 9); (b) CH3CO2H:H2O (4:1), reflux, 12 h (86% yield); (c) PhMgBr, THF,
0°C–rt, 30 h (74% yield a:b=3:1); (d) Ac2O, C5H5N, DMAP, 24 h (49% yield).
O
OAc O
OAc O
OAc O
b
a
C6H5
C6H5
C6H5
OAc OAc
OAc OAc
OAc OAc
1
6
2
Scheme 3. Reaction conditions: (a) Grubb’s catalyst (5 mol%), DCM, rt, 24 h (90% yield); (b) PCC, C5H5N, DCM, reflux, 8 h
(68% yield).

G. S. C. Srikanth et al. / Tetrahedron Letters 43 (2002) 5471–5473
5473
Acknowledgements
8. Yang, Z.-C.; Zhou, W.-S. Tetrahedron 1995, 51, 1429.
9. Gracza, T.; Jager, V. Synthesis 1994, 1359.
1
10. Compound 6: [h]2D5 −152.1 (c 0.2, MeOH): H NMR (300
G.S.C.S. would like to thank IIT Bombay and U.M.K.
to DST for a fellowship. We wish to thank Professor P.
Mathur and the National Single Crystal X-Ray Diffrac-
tion Facility at IIT Bombay. Also Dr. Shilpa Korde
and Dr. Dinesh Rele are highly acknowledged for their
helpful discussions.
MHz, CDCl3): lH 7.34 (m, 5H), 6.01 (m, 3H), 5.52 (t,
J=5.4 Hz, 1H), 4.97 (m, 1H), 4.30 (part of an AB
system, J=19.8 Hz, 1H), 4.08 (part of an AB system,
J=19.8 Hz, 1H), 3.55 (dd, J=2.5, 5.12 Hz, 1H), 2.09 (s,
3H), 2.08 (s, 3H), 2.07 (s, 3H). 13C NMR (75 MHz): lC
170.3, 169.6, 136.5, 131.8, 128.6, 126.9, 122.2, 74.2, 73.5,
73.1, 66.1, 65.49, 20.96, 20.92, 20.86.
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