The enantiodivergent total synthesis of natural and unnatural enantiomers of theobroxide

Kamikubo, Takashi; Ogasawara, Kunio

doi:10.1016/0040-4039(95)00131-u

Cited by 43 publications

(40 citation statements)

References 18 publications

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“…b-Hydroxyketone 6 was obtained in three steps from (À)quinic acid (5) in excellent yields, as previously described in the literature. In Scheme 1 the initial common steps for these syntheses are depicted.…”

Section: Resultsmentioning

confidence: 99%

“…[2b] There is also only one synthesis of theobroxide described in the literature so far, [5] and two syntheses [5,7] of epiepoformin, one of them racemic, [7] the other relied upon a retro-Diels-Alder reaction for the liberation of the unsaturated product. [5] To our knowledge, (À)-asperpentyn has not been previously synthesised and our synthesis confirms the structure proposed after its isolation. [3] (À)-Quinic acid (5), an abundant natural substance has, besides a cyclohexane skeleton, a masked 1,4-oxygen functionality suitable for synthesis of the necessary hydroxyl and [ carbonyl groups in these positions of the target compounds.…”

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confidence: 99%

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The First Synthesis of (−)-Asperpentyn and Efficient Syntheses of (+)-Harveynone, (+)-Epiepoformin and (−)-Theobroxide

Barros¹,

Maycock²,

Ventura³

2000

Chem. Eur. J.

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A generally applicable strategy for the synthesis of a range of polyoxygenated cyclohexane natural products has been developed. The enantioselective syntheses of (-)-theobroxide, a polyoxygenated cyclohexane natural compound with potent growth inducing properties in potato microtubers has been achieved via a 1,2 O-silyl migration between trans-hydroxyl groups and a remote hydroxyl directed epoxidation of an enone derived from quinic acid. A thus derived alpha-iodoenone was subjected to Stille coupling with tetramethylstannane to afford the first title compound. A similar strategy enabled a route to the complete asymmetric synthesis of the acetylenic phytotoxin (+)-harveynone. By selective reduction of (-)-theobroxide, (+)-epiepoformin was also prepared in enantiopure form and similarly, stereoselective reduction of (+)-harveynone completed the first enantioselective synthesis of (-)-asperpentyn, another natural compound with antimicrobial activity.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

The First Synthesis of (−)-Asperpentyn and Efficient Syntheses of (+)-Harveynone, (+)-Epiepoformin and (−)-Theobroxide

Barros¹,

Maycock²,

Ventura³

2000

Chem. Eur. J.

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“…Ogasawara [19] and Maycock [22] synthesized both enantiomers of 8 and the natural one, respectively, by applying the strategies described above, while Arimoto [25] recently published an enantioselective synthesis of (À)-8 based on photooxygenation of 1-methyl-1,4-cyclohexadiene and enzymatic resolution of an immediate precursor.…”

Section: Introductionmentioning

confidence: 98%

“…The natural enantiomer has been synthesized by several authors using different strategies: Ogasawara et al [19] based their approach on a retro-Diels-Alder reaction to recover the cyclohexenone fragment from a stereoselectively functionalized quinone Diels-Alder adduct, previously asymmetrized by isomerization with an enantiopure BINAP-Rh I catalyst, [20] while the formation of a bicyclic adduct in a cinchonine-catalysed reaction between 3-hydroxy-2-pyrone and an acrylamide derived from a chiral oxazolidinone was the key step in the approach of Okamura et al [21] (À)-Quinic acid was the starting material in the synthesis reported in 2000 by Maycock et al, [22] , whereas a chiral building block obtained by enzymatic reduction was used by Kitahara et al [23] to synthesize (+)-7 in 2003.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of Natural Polyoxygenated Cyclohexanes and Cyclohexenes from [(p‐Tolylsulfinyl)methyl]‐p‐quinols

Carreño

Merino

Ribagorda

et al. 2007

Chemistry A European J

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Exploitation of the beta-hydroxysulfoxide fragment present in a number of enantiomerically pure (SR)- and (SS)-[(p-tolylsulfinyl)methyl]-p-quinols allowed chemo- and stereocontrolled conjugate additions of different organoaluminium reagents to the cyclohexadienone moiety. The same fragment was also shown to act as an efficient chiral masking carbonyl group, after oxidation to sulfone and retroaddition in basic medium, with elimination of methyl p-tolyl sulfone. Through the use of both transformations as key steps, enantiocontrolled syntheses of different natural products-such as the two enantiomers of dihydroepiepoformin, (-)-gabosine O, (+)-epiepoformin, (-)-theobroxide and (+)-4-epigabosine A (an epimer of the natural product gabosine A)-has been achieved. The presence of the beta-hydroxy sulfone moiety makes the cyclic structures rigid, allowing a number of stereoselective transformations such as carbonyl reductions, enone epoxidations or cis-dihydroxylations, en route to the natural structures. The observed selectivities were dependent on the particular substitution in each substrate, providing evidence of a strong influence of remote groups on the preferred approach of the reactants to the reactive conformations. An advanced precursor of natural (+)-harveynone was also synthesized, but the isolation of the natural product was not possible because of the instability of the corresponding enone, containing a triple bond, under the basic conditions necessary to eliminate the beta-hydroxy sulfone. This demonstrated that the limitations of the use of the beta-hydroxy sulfoxide as a chiral protecting carbonyl group were dependent on the relative stabilities of the final targets in the presence of the required base.

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“…Using Ogasawara's previously reported protocol, the authors also obtained (+)-epiepoxydon and (+)-epiepoformin from 266 [139,140]. ent-Phyllostine (ent-27) was obtained starting from the endo Diels-Alder adduct 268 that was obtained by deiodinating 263 [141].…”

Section: Ryu's Methodologymentioning

confidence: 99%

Enantioselective Synthesis of Natural Epoxyquinoids

Pandolfi

Schapiro²,

Heguaburu³

et al. 2013

COS

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Natural products play an important role as a source not only of potential therapeutic drugs but also of starting materials for semisynthetic new medicines. The epoxyquinoid family, composed by cyclohexane epoxides and related structures, exhibit these characteristics without doubt.Since 2004, significant efforts have been devoted to the stereocontrolled synthesis of these molecules with different and interesting strategies. More than 50 works on this field have been published during this period of time. In addition, many of these polyoxygenated cyclohexenoids exhibit diverse and impressive bioactive shapes. This review aims to analyze the recent advances in the enantioselective processes that have been performed for the total syntheses of these target molecules. It includes a wide range of methodologies for the introduction of chirality either enzymatic or chemical ones. This summarizes microbial preparation of starting materials, lipase kinetic resolutions, use of compounds from the chiral pool, use of chiral auxiliaries and asymmetric catalysis. In a special section, syntheses of scyphostatin are also included.

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The enantiodivergent total synthesis of natural and unnatural enantiomers of theobroxide

Cited by 43 publications

References 18 publications

The First Synthesis of (−)-Asperpentyn and Efficient Syntheses of (+)-Harveynone, (+)-Epiepoformin and (−)-Theobroxide

The First Synthesis of (−)-Asperpentyn and Efficient Syntheses of (+)-Harveynone, (+)-Epiepoformin and (−)-Theobroxide

Enantioselective Synthesis of Natural Polyoxygenated Cyclohexanes and Cyclohexenes from [(p‐Tolylsulfinyl)methyl]‐p‐quinols

Enantioselective Synthesis of Natural Epoxyquinoids

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