Mining the Tetraene Manifold: Total Synthesis of Complex Pyrones from Placobranchus ocellatus

Abstract

A natural product anticipated through total synthesis! Ocellapyrone A was obtained in the laboratory several months before the structure of this unusual natural product (see scheme) was reported. An isomerization/8π–6π electrocyclization cascade was used for the formation of the natural product from a polyene precursor. The synthesis of ocellapyrone B from a diastereomer of ocellapyrone A was also performed.

Transition metals in organic synthesis: Highlights for the year 2005

“…Synthetic targets include, the heterocyclic core of GE 2270 [34], peridinin [35], pyrones isolated from placobranchus ocellatus [36], terpenepolyketide natural products [37], dihydroxerulic and xerulinic acid [38], bipinnatin J [39], elipticine [40], (+)-7-deoxytrans-dihydronarciclasine [41], gambierol [42], taiwaniaquinol [43], (−)-scabronine G [44], garsubellin A [45], piericidin A1 and B1 [46], lucilactaene [47], fostriecin [48], lupine alkaloids [49], ␤-C-glycosides [50], (+)-crocacin D [51], lobatamide analogs [52], epoxyquinoid compounds [53,54], (+)-SCH 351448 [55], 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids [56], (+)-ochromycinone and (+)-rubiginone B 2 [57], EI-1941-1 and EI-1941-2 [58], mycothiazole [59], 6 -epiperidinin [60], aureothin and N-acylaureothamine [61], cyercene A and placidenes [62], herbindole B [63], (+)-tubelactomicin A [64], saudin [65], peroxyacarnoates A and D [66], aureothin, N-acetylaureothamine, aureonitrile [67], elysiapyrones [68], altromycin B [69], (+)-phorboxazole A and analogues [70,71], (−)-SNF4435 C and (+)-SNF4435 D [72], A2E [73], paracentrone [74]<...>…”

Peroxy natural products

“…154 The same species, P. ocellatus, provided the possibly artefactual peroxy derivative 279, 155 whose relative configuration was confirmed at the same year. 156 A Panamanian collection of the sacoglossan mollusc Elysia diomedea yielded the endoperoxide 280, structurally closely related to 279. 157 The observation of rearrangement of 280 with triethylamine to yield the known vicinal diexpoxide elysiapyrone A 158 prompted speculation of the biosynthetic intermediate of 280, likely to be in turn derived from a putative polypropionate alkenyl chaincontaining precursor reacting with singlet oxygen.…”

Biomimetic Electrocyclization Reactions toward Polyketide‐Derived Natural Products

“…The biomimetic synthesis of 9,10-deoxytridachione (15) was independently achieved by Baldwin et al [29] and Trauner et al [30]. Both research groups utilized a convergent cross-coupling approach to assemble the (2E,4Z,6E,8E)-polyene-pyrone 18, which was perfectly set up to undergo a 6π disrotatory electrocyclization to give the target cyclohexadiene 15.…”

“…The powerful sequence involving double bond isomerization followed by electrocyclization cascades has been further developed by the research groups of Baldwin [29] and Trauner [30] in their syntheses of the molluscan polypropionate ocellapyrone A (27) [33]. Although the original synthetic target of both groups was 9,10-deoxytridachione (15) (Scheme 16.9), the key (2E,4Z,6E,8E)-tetraene 18 arrived at by both research groups was found to undergo further double bond isomerization to give the (2E,4Z,6Z,8E)-polyene 29.…”

“…Diastereomer 34 is the product arising from exo-orientation of the ethyl group, whereas compound 27 arises from endo-orientation (Scheme 16.25). To access the (2E,4Z,6Z,8E)-polyene 29 directly, Trauner [30] synthesized the vinyl stannane 116 and vinyl iodide 24, which were coupled using the conditions of Mee et al [31]. Polyene 29 was not isolated, and underwent the electrocyclic cascade directly to give isomers 27 and 34.…”