An enantioselective approach to 3.alpha.-hydroxy-15-rippertene. Construction of the tetracyclic ring system

Iso‐seco‐tanapartholides: Isolation, Synthesis and Biological Evaluation

“…In practice, acid-mediated elimination of acetic acid from 12 ,13 obtained from 11 ,12 provided 8 in accordance with literature precedent. Subsequent dihydroxylation of 8 gave syn -diol 9 as the major component in a 3:1 mixture with 13 , with the reaction occurring exclusively at the γ,δ-double bond in 8 .…”

Enantioselective Synthesis of 4‐Desmethyl‐3α‐hydroxy‐15‐rippertene

“…Several years ago we developed an enantioselective approach to the ring system of 1 from the commercially available sesquiterpene lactone (À)-a-santonin. [6] Furthermore, we recently accomplished the enantioselective preparation of the hydroazulene moiety of 1, commencing with (À)-isopulegol. [7] Herein we report on the first enantioselective synthesis of 4-desmethyl-3a-hydroxy-15-rippertene (2), a close analog of 1, starting from the cyclohexanone 5, which is efficiently made in only four steps from (À)-isopulegol.…”

“…[24] Construction of the tetracyclic rippertene core was achieved by an efficient intramolecular Diels-Alder reaction from the cyclization precursor 14, which was made by the diastereoselective reduction of 13 and subsequent etherification using propargyl bromide. [6] Compound 14 then underwent isomerization under basic conditions to give the corresponding allenyl ether, which then cyclized under microwave irradiation to yield the enol ether 4 with complete diastereoselectivity. [25] For completion of the norditerpene 2, enol ether 4 was first converted into the lactone 15 by hydration [26] and subsequent TPAP oxidation [27] (Scheme 4).…”

Enantioselective Synthesis of the Hydroazulene Core of 3α‐Hydroxy‐15‐rippertene

“…So far, the total synthesis of a single naturally occurring kempane, kempene-2, [3] has been achieved in racemic form, and many advanced synthetic investigations directed to this class of natural products have been reported. [4,5] We recently reinitiated our studies toward the enantioselective total synthesis of the diterpene 3α-hydroxy-15-rippertene (1) that has been isolated from the defense secretion of the higher termites Nasutitermes rippertii and Nasutitermes ephratae by Prestwich [6] ( Figure 1). Several years ago, we accomplished the first enantioselective construction of the tetracyclic skeleton of 1 starting from the sesquiterpene lactone (-)-α-santonin.…”

“…Several years ago, we accomplished the first enantioselective construction of the tetracyclic skeleton of 1 starting from the sesquiterpene lactone (-)-α-santonin. [5] Herein we disclose a concise synthetic sequence to two advanced key intermediates 4a and 4b containing the complete hydroazulene moiety of 1 by commencing with (-)-isopulegol (6) as the chiral source. As outlined in Figure 1, a domino Heck cyclization [7] of enol triflate 3 is envisioned to generate the tetracyclic ring system, and the hydroazulenes 4a and 4b represent suitable precursors for this intermediate; 4a and 4b, in turn, should be available from the cycloheptenone 5 by cyclopentene annulation, while 5 can be retrosynthetically traced back to (-)-isopulegol (6) by a sequence of chain elongation, oxidation and ring expansion.…”