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

Abstract

Let it rip: An intramolecular Diels–Alder reaction and two intramolecular aldol condensations allow the efficient preparation of the title compound 2, a close analogue of the diterpene 1 which was isolated from the defense secretion of termite soldiers. The synthesis commenced with cyclohexanone 3, which is rapidly available from (−)‐isopulegol.

A Dipleiadiene‐Embedded Aromatic Saddle Consisting of 86 Carbon Atoms

“…In view of the above difficulties,w ec onsidered ring expansion [27] of the cyclohexanone moieties in bisanthenequinone as an alternative approach to the polycyclic framework of 6,a sshown in Scheme 2a.H owever, unsubstituted bisanthenequinone [23] is not ag ood substrate for the ring expansion because of its very poor solubility in common organic solvents.T reatment of bisanthenequinone with trimethylsilyldiazomethane (TMSCHN 2 ) [28,29] at the presence of Lewis acid did not result in isolation of the desired product. To increase the solubility,four t-butyl groups were introduced to bisanthenequinone.Asshown in Scheme 2b,tetra(t-butyl) bisanthenequinone (10) [30] was synthesized from di(t-butyl)anthrone (11) [31] by oxidative coupling and the subsequent photocyclization in good yields.T he ring expansion of 10 using TMSCHN 2 resulted in diketone 13 as one constitutional isomer,t he structure of which however has not been determined with respect to the positions of carbonyl groups, as shown in Scheme 2b.T reatment of 13 with LDAfollowed by quenching with triflic anhydride led to ditriflate 14.…”

Enantioselective Total Synthesis of 3β‐Hydroxy‐7β‐kemp‐8(9)‐en‐6‐one, a Diterpene Isolated from Higher Termites

“…The defense secretion of higher termite soldiers is a rich source of structurally fascinating tetracyclic diterpenes with so far mostly unknown bioactivities (Figure ) . Only in 2013, a significant activity of 3α‐hydroxy‐15‐rippertene ( 3 ) against methicillin‐resistant S. aureus was reported by Rezende and co‐workers, while we also found antibiotic activity for the 4‐desmethyl analogue of 3 against B. subtilis earlier . Synthetically, these natural products are largely unexplored as well.…”

Synthesis of 4- Desmethyl -Rippertenol and 7- Epi -Rippertenol via Photoinduced Cyclization of Dienones

“…The enantioselective version was then completed by following up the racemic route, and both the spectral and optical rotations of 2 matched those reported by Hennig and Metz. 31 Finally, we aimed for the total synthesis of rippertenol 1. As illustrated in Scheme 4, treatment of tetracyclic compound 29 with aqueous hydrogen fluoride in a mixed solvent (MeCN/DCM) removed the tertbutyldimethylsilyl group, and alcohol 39 was obtained in 78% yield.…”

“…27,28 Considering these synthetic challenges, Metz′s group 29,30 made unremitting efforts to access this molecule. In 2009, they finished an asymmetric synthesis of 4-desmethyl-rippertenol 2, 31 an analog of 1 with antibiotic activity against Bacillus subtilis, 32 through reaction sequences involving the ring expansion of cyclohexanone to cycloheptanone and an intramolecular Diels-Alder reaction. After that, Snyder′s group 33 completed the first total synthesis of rippertenol in 2011 utilizing an inverse Diels-Alder reaction and late-stage ring expansion to forge the fused cycloheptanoid structure.…”