Synthetic Studies Towards the ent-Labdane Diterpenoids: Rearrangement of ent-Halimanes

Abstract

Abstract:For the first time ent-labdanes have been synthetised starting from ent-halimic acid, following a route that is the reverse of the biosynthetic one leading to the former compounds.

Halimane diterpenoids: sources, structures, nomenclature and biological activities

“…The natural product structure of 3a-hydroxy-5b,10b-epoxychiliolide (214) was corroborated by the synthesis of the racemic diterpene (Scheme 15). 182 The synthesis starts with the available tetralone 308.…”

“…A structural characteristic of this group of compounds (208)(209)(210)(211)(212)(213)(214)(215)(216)(217)(218)(219) is that all of them show oxygenated functions at C5, except diasin (219, from Croton diasii), 176 which we include in this group precisely for not having any unsaturation in the decalin system ( Fig. 15, Table S4 †).…”

Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes

“…In this regard, van Tamelen and Sharpless reported in 1969 that the treatment of squalene-2,3-oxide with stannic chloride led to a mixture of cyclized products, including a rearranged bicyclic alcohol possessing the halimane core. , Apart from van Tamelen’s seminal work, to the best of our knowledge, no precedents exist on addressing rationalized synthesis of “rearranged terpenes” using this approach. However, efficient rearrangements of carbocations generated on previously cyclized structures can be found in the literature. − Some of these nonenzymatic rearrangements can be considered as good examples of the minimal-enzymatic-assistance hypothesis, , thus encouraging the biomimetic pursuit of these complex reactions.…”

The Methylene-Cycloalkylacetate (MCA) Scaffold in Terpenyl Compounds with Potential Pharmacological Activities

“…Figure 5 shows some of the diterpene or sesquiterpene derivatives synthesized from ent -halimic acid: 1. ent -halimanolides [2,56,57,58]; 2. chettaphanin I and II [4,5]; 3. sesterterpenolides [6,59,60]. Figure 6 shows other groups of compounds prepared from 2 , among which are as follows: 4. hybrid compounds: sesterterpenolide bioconjugates and glycerophospholipids [61]; 5. rearranged derivatives: ent -labdanes [62], abeopicrasanes [63], and a propellane [64]; 6. sequiterpene-quinone/hidroquinones [65]; 7. terpene alkaloids: sesqui- and diterpene-alkaloids [7,8,66,67,68,69].…”

“…This rearrangement will be the opposite to the biosynthetic route in which the ent -labdanes are the precursors of ent -halimanes. For the first time, ent -labdanes have been synthesized starting from ent -halimic acid methyl ester 2 , following a route that is the reverse of the biosynthetic one leading to the former compounds [62] (Scheme 7). Effectively, the ent -halimane epoxyderivative 143 , formed in three steps from 2 , led to the ent -labdane tetranorderivative 144 by treatment with Lewis acid.…”