Total Synthesis of Sporolide B and 9-epi-Sporolide B

Abstract

The total synthesis of the structurally unique secondary metabolite sporolide B (1b, Figure 1) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37, Scheme 5; 75, Scheme 11) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to sporolide model system 4 (Figure 1), 9-epi-sporolide B (5, Figure 1), and sporolide B (1b). The requisite indene o-quinone precursor (75, Scheme 10) was synthesized through a rutheniumcatalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol (42, Figure 8) and a chloroacetylenic cyclopentenyne (64, Scheme 9) followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus.

The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery

“…Although there was no biological activity reported for sporolides A and B, in silico target prediction showed a maximum docking score with HIV-1 reverse transcriptase, with the activity of sporolide B confirmed in vitro using a fluorescent assay 89 . A synthesis of the sporolide ring framework has been achieved 90 along with the total synthesis of sporolide B 91, 92 .…”

Utilization of catecholic functionality in natural safrole and eugenol to synthesize mussel-inspired polymers

“…As a model case, safrole 1 was used for examining the deprotection aspect using lead tetraacetate. 42,61 To our relief, safrole 1 on treatment with the oxidizing agent afforded 9 having labile acetoxy group (Scheme 2). In fact, the similar acetoxy derivatives are usually removed during aqueous work up leading to catechol motifs.…”

“…The ltrate was dried (Na 2 SO 4 ) and evaporated to obtain polymer 8.2.6. Activation of methylene acetal of safrole 1 as a model case42,43 Pb(OAc)4 (4.23 g, 9.5 mmol) was added under N 2 to a solution of safrole 1 (1.05 g, 6.48 mmol) in benzene (35 mL) at 75 C and stirred for 3 h. The reaction mixture was taken up in EtOAc (30 mL) and washed with H 2 O (3 Â 25 mL). The organic layer was dried (Na 2 SO 4 ) and concentrated.…”

Metallacycle-mediated cross-coupling in natural product synthesis

“…154, 155 As illustrated in Figure 45B, Ru-catalyzed coupling of the terminal alkyne 107 with the chlorinated diyne 108 proceeded to deliver 109 in 87% yield as a single regioisomer – the product derived from selective reaction of alkyne 107 at the less hindered C–Ru bond of the metallacyclopentadiene (generated from 108 ) where alkyne 107 is oriented in such a way to minimize unfavorable steric interaction with ligands at the Ru-metal center.…”