The polyhydroxy cyclopentene, a total synthesis of (-)-pentenomycin

Article abstract of DOI:10.1016/S0040-4039(00)00628-6

The functionalized cyclopentene 2 was converted in five steps to (-)- pentenomycin 1. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00628-6

Tetrahedron Letters 41 (2000) 4291±4293
The polyhydroxy cyclopentene, a total synthesis of
(^)-pentenomycin
Mohindra Seepersaud and Yousef Al-Abed*
The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
Received 23 February 2000; revised 24 March 2000; accepted 28 March 2000
Abstract
The functionalized cyclopentene 2 was converted in ®ve steps to (^)-pentenomycin 1. # 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: cyclopentenes; cyclopentenones; cyclization; antibiotics.
The pentenomycin antibiotics have attracted considerable attention due to its wide range of
structural and stereochemical features and biological activities.1a Pentenomycin 1 was isolated by
Umino and co-workers in 1973 from the culture broths of Streptomyces eurythermus,1b,c while
epipentenomycin the C-4 diastereomer, was isolated from carpophores of Perziza sp.2 There have
been several approaches3 to synthesize these antibiotics and their derivatives however, an expeditious
and ecient approach is still needed.
In connection, we recently reported the synthesis of a polyhydroxylated cyclopentene 2,4 a
useful template that can be widely utilized in synthesis of highly functionalized ®ve-membered
rings. The synthesis of 2 was done via a ring closing metathesis (RCM) in ®ve steps with a 90%
yield. A comparison of cyclopentene 2 with pentenomycin 1 indicates that the stereochemistry
around the C-4 and C-5 are identical. Therefore, logical retrosynthetic analysis suggests that our
key cyclopentene intermediate 2 can be converted to pentenomycin 1, via elaboration of precursor
3 (Scheme 1).
* Corresponding author. E-mail: yal-abed@picower.edu
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00628-6

4292
Scheme 1.
Thus, compound 2 was treated with BH3:THF to give the two regioisomeric alcohols 3 and 4
(2:1) (Scheme 2). The use of BH3:SMe2 gave no additional selectivity while catecholborane and 9-
borobicyclo[3.3.1]nonane gave no reaction.5 The structural identi®cation of these regioisomers 3
and 4 were based on the coupling constants of the new methylene protons at C-2 and C-1,
respectively (Scheme 2).
Scheme 2.
Compound 3 was oxidized by PCC to a€ord the corresponding ketone 5 (Scheme 3). Additional
con®rmation of the regiochemistry of the carbonyl group came from the coupling constants of
the C-2 methylene protons of 5, where two signals at ꢀ 2.30 (dd, J=7.7, 20.0 Hz, 1H) and ꢀ 2.79
(dd, J=7.4, 20.0 Hz, 1H) were observed. However, the corresponding ketone of the other
regioisomer 4 showed only one signal for the C-1 protons at ꢀ 2.61 (d, J=3.7 Hz, 2H).
The ketone 5 was hydrogenated, then treated with pyridine/acetic anhydride to furnish the
acetylated enone 6. Deprotection of the acetate 6 with tri¯uoroacetic acid/H2O a€orded (^)-penteno-
1
mycin 1 (Scheme 3). The H and 13C NMR of 6 and 1 were identical with those reported in the
literature.1,2,6
Scheme 3.
In summary, a concise and ecient synthesis of the (^)-pentenomycin 1 was demonstrated in
®ve steps (46% yield), using our key polyhydroxy cyclopentene intermediate 2.

4293
Acknowledgements
The authors wish to thank the Patterson foundation for their support and Dr. Kirk Manogue
for his help in the preparation of this manuscript.
References
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1
6. For compound 1: H NMR (D2O, 270 MHz) ꢀ 3.61 (ABq, Ád=0.07 ppm, 2H, J=11.6 Hz), 4.72 (dd, J=1.2, 2.7
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