C O M M U N I C A T I O N S
Scheme 2 a
fluoride-induced11 cleavage of ester 18 gave acid 19 in good overall
yield without racemization of the rather labile center at C-5.
Esterification of 19 with disaccharide 10, subsequent macrocy-
clization via RCM, and hydrogenation of the resulting E/Z mixture
with the aid of Wilkinson’s catalyst were all highly productive.
Following the protocol outlined above, treatment of 21 thus obtained
with TASF led to the simultaneous cleavage of the C-silyl and
O-silyl groups;12 final acid-catalyzed deprotection of the isopro-
pylidene acetal afforded ipomoeassin E (2) in high overall yield.
While the analytical and spectroscopic data of the synthetic material
nicely matched those of the natural product,1 we noticed a
1
previously unrecognized dependence of its H NMR spectrum in
C6D6 from the chosen dilution; for details, consult the Supporting
Information.
In summary, a concise and flexible entry into the family of the
cytotoxic ipomoeassin resin glycosides has been developed. The
successful route hinges upon the use of compound 8 as a new
cinnamic acid surrogate which meets the requirement of being
resistant to hydrogenation in the presence of homogeneous catalysts,
yet is easy to deprotect without compromising its configurational
integrity. An extension of our work to the other members of this
family and a series of unnatural congeners, as well as a first round
of biological evaluation, is ongoing and will be reported in due
course.
a Conditions: (a) Acid 8, 2,4,6-trichlorobenzoyl chloride, Et3N, DMAP,
toluene, 79% (over both steps from 5); (b) DDQ, CH2Cl2/H2O; (c) 4-oxo-
8-nonenoic acid, 2,4,6-trichlorobenzoyl chloride, Et3N, DMAP, toluene, 78%
(over both steps); (d) complex 12 (10%), CH2Cl2, reflux, 71%; (e) H2 (1
atm), RhCl(PPh3)3 (20%), EtOH, 81%; (f) TASF, MeCN; (g) trifluoroacetic
acid (TFA), CH2Cl2, 45% (over both steps).
Acknowledgment. Financial support by the MPG and the Fonds
der Chemischen Industrie is gratefully acknowledged.
Supporting Information Available: Experimental section including
the preparation of the building blocks and copies of the NMR spectra
of new compounds. This material is available free of charge via the
Scheme 3a
References
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(b) Fu¨rstner, A.; Albert, M.; Mlynarski, J.; Matheu, M.; DeClercq, E. J.
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(7) For details, consult the Supporting Information.
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a Conditions: (a) t-BuOOH, VO(acac)2 (2%), CH2Cl2, 71%; (b) CrO3,
H2SO4, acetone, 0 °C; (c) Zn, HOAc, CH2Cl2, 78% (over both steps); (d)
(i) HO(CH2)2SiMe3, p-TsOH cat., CH2Cl2; (ii) Ac2O, DMAP cat., CH2Cl2,
93% (over both steps); (e) TASF, DMF, 68%; (f) compound 10, 2,4,6-
trichlorobenzoyl chloride, Et3N, DMAP, toluene, 87%; (g) complex 12
(10%), CH2Cl2, reflux, 85%; (h) H2 (1 atm), RhCl(PPh3)3 (20%), EtOH,
83%; (i) TASF, MeCN; (j) TFA, CH2Cl2, 63% (over both steps).
forward (Scheme 3). A scalable route to the required acid segment
19 was found by a Sharpless-type kinetic resolution of furyl alcohol
(()-157,13 followed by oxidative rearrangement of (-)-15 (ee
>99%) thus obtained with the aid of t-BuOOH and catalytic
amounts of VO(acac)2.14 Subsequent oxidation of the hemiacetal
in 16, conjugate reduction of the resulting enone with Zn dust,
opening of lactone 17 thus formed with trimethylsilylethanol, and
(14) Ho, T.-L.; Sapp, S. G. Synth. Commun. 1983, 13, 207.
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