Azedaralide: total synthesis, relative and absolute stereochemical assignment

Synthesis of Limonoid Natural Products

“…[28] Azadarelide (44) is a δ-lactone degraded limonoid that has been isolated from M. azedarach. [8] Degraded limonoids such as 41, 42 and 44 have the required functionality and stereochemical configuration to act as advanced intermediates for synthetic campaigns targeting more complex tetranortriterpenoids. [8] Degraded limonoids such as 41, 42 and 44 have the required functionality and stereochemical configuration to act as advanced intermediates for synthetic campaigns targeting more complex tetranortriterpenoids.…”

“…For example, calendrolide (42) retains a common C/D ring substructure with the abundant citrus bitter principle limonin [1] (45), a long known molecule that has not yet succumbed to total synthesis efforts in spite of insightful pioneering efforts by the Suarez group. [8] The following section details the comprehensive synthetic efforts toward the δ-lactone degraded limonoids starting with pyroangolensolide, a molecule that has received considerable attention from the synthetic community over the last 25 years. [8] The following section details the comprehensive synthetic efforts toward the δ-lactone degraded limonoids starting with pyroangolensolide, a molecule that has received considerable attention from the synthetic community over the last 25 years.…”

“…Upon close inspection of TS-I, it was hypothesized by Williams and co-workers [8] that increased steric bulk at the allylic methyl position should be well accommodated without disruption of reactant approach or erosion of the exquisite stereocontrol of the reaction. Indeed, the silyl ether 60 (Scheme 7, B) could be processed through the stereospecific Fernández-Mateos synthetic protocol to provide azadaralide (44) in large quantities and with comparable efficiency (eight steps, 19 % overall yield) to the original sequence.…”

“…[1][2][3] The most recognizable intact limonoid amongst the synthetic organic community may be azadiradione (84), [3a] the subject of a renowned synthesis campaign completed in the late 1980's. [7,8] seco-Limonoids are modified triterpenes that have undergone oxidative fission of one or more of the androstane rings as per the IUPAC recommendations [4a] for use of the prefix seco-with regard to generic steroid nomenclature. [7] Members of this subclass are derived from intact tetranortriterpenoids and frequently share a common ring substructure with other terpenoid natural products.…”

Cyclic Enones as Substrates in the Morita–Baylis–Hillman Reaction: Surfactant Interactions, Scope and Scalability with an Emphasis on Formaldehyde

“…[2] In fact, our own synthetic endeavours have seen the utilisation of the MBH reaction in the early stages of total synthesis campaigns, for example, azedaralide 1 [3] and 2-O-methylneovibsanin H 2 [4] (Scheme 1) from MBH products 3 and 4, respectively. [5] Activities in this area quickly highlighted problems associated with the reactivity of cyclic enones and formalin under MBH conditions (e.g., conversion of cyclohexenones 5 and 6 to MBH products 3 and 4), in particularly isolated yield and reaction scale, facets critical to resolve for future work and the greater synthetic community.…”