Reconciling Icetexane Biosynthetic Connections with Their Chemical Synthesis:  Total Synthesis of (±)-5,6-Dihydro-6α-hydroxysalviasperanol, (±)-Brussonol, and (±)-Abrotanone

Simmons, Eric M.; Yen, Jennifer R.; Sarpong, Richmond

doi:10.1021/ol0712428

Cited by 50 publications

(35 citation statements)

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“…(+)-dichroanone (40 A related successive oxidation of a catechol substrate has been reported by Sarpong in the synthesis of abrotanone (43) from brussonol (41) [19]. This process involves a four-electron oxidation with the addition of two methanol equivalents in a regioselective fashion.…”

mentioning

confidence: 85%

Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

Jackson

Pettus

2011

Biomimetic Organic Synthesis

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mentioning

confidence: 85%

Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

Jackson

Pettus

2011

Biomimetic Organic Synthesis

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“…Subsequent alkylation of β-ketoester 22 with alkyl iodide 23 11a at 65 °C led to adduct 24 in 66% yield over the two steps.…”

Section: Resultsmentioning

confidence: 99%

“…On the basis of our previous synthetic studies on the icetexane diterpenoid salviasperanol, 11a we anticipated that oxygenation at the C10 position of diene 29 could occur through a chemoselective epoxidation of the tetrasubstituted olefin. We were pleased to observe exclusive formation of vinyl oxirane 41 (as a single diastereomer) when diene 29 was treated with m -CPBA.…”

Section: Resultsmentioning

confidence: 99%

“…To a solution of the crude β-ketoester ( 22 , 783 mg, 2.43 mmol) in acetone (10 mL) in a Schlenk flask was added K 2 CO 3 (1.01 g, 7.28 mmol), and the resulting suspension was stirred at rt for 15 min. A solution of 23 11a (573 mg, 2.43 mmol) in acetone (6 mL) was added, and the flask was evacuated and backfilled with N 2 (3×). The flask was sealed and heated to 65 °C for 40 h. After cooling to rt, the mixture was diluted with water (30 mL) and extracted with Et 2 O (3×30 mL).…”

Section: Methodsmentioning

confidence: 99%

“…This methodology was subsequently applied to the total synthesis of several members of the icetexane diterpenoid family. 11 …”

Section: Introductionmentioning

confidence: 99%

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Synthetic studies on the icetexones: enantioselective formal syntheses of icetexone and epi-icetexone

et al. 2013

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Two strategies for the synthesis of the icetexane diterpenoids icetexone and epi-icetexone that rely on Ga(III)-catalyzed cycloisomerization of alkynyl indene substrates to yield fused [6-7-6] tricycles have been explored. In the first approach, access to a tricycle bearing a gem-dimethyl group paved the way for explorations of C–H functionalization of one of the methyl groups in close proximity to a hydroxyl-directing group. This approach was ultimately unsuccessful and led only to ring cleaved products. In the second approach, an alkynyl indene substrate bearing a cyano substituent was utilized, which was effective in providing a functional handle to access the icetexone subclass of diterpenoids. A key epoxide opening/diazene rearrangement sequence was utilized to complete a formal synthesis of icetexone and epi-icetexone, which is discussed in detail. Furthermore, the cyano-containing substrate has been prepared in enantioenriched form using a Rh-catalyzed conjugate addition reaction, which now provides a route to the enantioselective synthesis of these natural products.

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The Barton‐McCombie Reaction

2012

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Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

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Reconciling Icetexane Biosynthetic Connections with Their Chemical Synthesis: Total Synthesis of (±)-5,6-Dihydro-6α-hydroxysalviasperanol, (±)-Brussonol, and (±)-Abrotanone

Abstract: A unified strategy for the chemical synthesis of the icetexane diterpenoids brussonol and 5,6-dihydro-6alpha-hydroxysalviasperanol has led to a structural revision of the recently isolated natural products abrotandiol and abrotanone.

Cited by 50 publications

References 13 publications

Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

Synthetic studies on the icetexones: enantioselective formal syntheses of icetexone and epi-icetexone

The Barton‐McCombie Reaction

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