Total Syntheses of (±)-Omphadiol and (±)-Pyxidatol C through a Cis-Fused 5,7-Carbocyclic Common Intermediate

Abstract

Total syntheses of omphadiol and pyxidatol C, two isomeric africanane sesquiterpenes sharing identical 5-7-3 tricyclic carbon skeletons yet containing distinct oxidation patterns, are reported. The trans-fused 5,7-carbocycles in the terpenoids characterized by specific oxidation patterns were derived from a readily available cis-fused 5,7-carbocyclic common intermediate.

Recent advances in the synthesis of natural multifunctionalized decalins

“…Total synthesis of racemic omphadiol and pyxidatol C, two isomeric africanane sesquiterpenes sharing identical 5-7-3 tricyclic carbon skeleton, has been achieved by Liang. 73 The formation of the cis-fused 5-7-carbocyclic common intermediate A relevant process involving an enantioselective copper(I)catalyzed borylative aldol cyclization of enones has been developed by Lam to deliver decalins containing four contiguous stereocenters, two of them being quaternary. 74 This domino sequence is based on the trapping of a copper enolate by a pendant ketone.…”

“…Total synthesis of racemic omphadiol and pyxidatol C, two isomeric africanane sesquiterpenes sharing identical 5-7-3 tricyclic carbon skeleton, has been achieved by Liang. 73 The formation of the cis-fused 5-7-carbocyclic common intermediate (AE)-150 is realized by a Tiffeneau-Demjanov rearrangement from trans-decalin (AE)-149. The synthesis starts with an aldol-Henry cascade and subsequent Parikh-Doering oxidation which allow isolation of the desired decalin precursor (AE)-148 in 45% yield from ketone 147.…”

Synthesis of Macrocyclic Ketones through Catalyst-Free Electrophilic Halogen-Mediated Semipinacol Rearrangement: Application to the Total Synthesis of (±)-Muscone

“…Applications of one-carbon ring-expansion reactions in the preparation of medium-ring and macrocyclic ketones have emerged in recent years, partly due to the availability of substrates and potential in the development of asymmetric variant. For instance, Tiffeneau–Demjanov rearrangement and homologation of cyclic ketones with diazo compounds have been reported (Scheme , eqs 2 and 3). However, Tiffeneau–Demjanov rearrangement requires strong acidic conditions, which suffers from low functional group compatibility .…”

Synthesis of (+)-Omphadiol and (+)-Pyxidatol C

“…Their synthesis involved introduction of the six contiguous stereogenic centers by substrate-controlled operations from ( R )-carvone without using protecting groups. Recently, a racemic total synthesis of omphadiol and pyxidatol C from a common intermediate was reported by Liang and co-workers, who utilized a stereospecific Tiffeneau–Demjanov rearrangement and an aldol–Henry cascade to prepare the trans -decalin core present in both natural products.…”

“…As in (+)-omphadiol, the four contiguous stereogenic centers are located at the juncture of the tricyclic skeleton, making it a challenging synthetic target. To date, only one racemic total synthesis has been reported …”