Ring eremantholide

In 1995 we accomplished the total synthesis of (+)-eremantholide A (8). Our synthetic scheme was completely different from that of the Boeckman group. We selected our building block 2 as the starting material, and the retrosynthetic analysis is outlined in Scheme 6. At first, disconnection of two carbon-carbon bonds in 8 as depicted leads to two fragments, an A/B ring equivalent 55 and known disubstituted 3(2if)-furanone derivative 56. We planned the direct connection of intact 3(2if)-furanone 56 to 55 at a... 

In the initial period of our synthetic efforts on the construction of the A/B ring equivalents, we had prepared two functionalized tetrahydrofuran-3-ones 62 and 64 from 2 (Scheme 7). We experienced at that time much difficulty in the C7-C8 bond formation (the eremantholide numbering) by means of an intramolecular aldol (62 to 63) or an intramolecular Horner-Emmons (64 to 65) reaction. After throughout investigations examined using theses and related substrates, we finally abandoned the A/B ring construction by means of these base-mediated "polar" carbon-carbon bond forming reactions. 

Ramberg-Backlund rearrangement. The key step in a synthesis of (+)-eremantholide A (4), involves ring contraction of the chloro sulfone 2 by the Ramberg-Backlund rearrangement. Thus treatment of 2 with this highly hindered base (1), 2.2 equiv., and HMPA (10 equiv.) in DME at 70° provides 3 in 82% yield. Use of less hindered bases results mainly in reduction of the chloro group. 

The fused cyclopentane 25 has been prepared by radical cyclization via deoxygenation of 24 (Scheme 4). This ring system is a carbocyclic analogue related to the A/B ring system of the cytotoxic sesquiterpene, (+)-eremantholide. 

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