Simple and efficient synthesis of thysanone methyl ether

Bulbule, Vivek J.; Koranne, Priti S.; Deshpande, V. H.; Borate, Hanumant B.

doi:10.1016/j.tet.2006.10.038

Cited by 16 publications

(7 citation statements)

References 25 publications

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“…5,17 Finally, following the literature procedure, 5 radical bromination of pyranonaphthoquinone 8 gave a mixture of diastereomeric bromides that were hydrolysed in aqueous tetrahydrofuran to deliver (-)-thysanone (1) 18 in excellent yield (Scheme 3). The 1 H NMR, 13 C NMR, and infrared spectra and melting point of our synthetic material were in agreement with both natural thysanone 4 and synthetic thysanone. 5 In addition, the specific rotation of our synthetic material at dilute concentration {[a] D 24 -21.2 (c = 0.003, MeOH)} is of a similar sign and magnitude to the reported specific rotation of the synthetic material obtained from the first total synthesis {[a] D -29.7 (c = 0.002, MeOH)}.…”

Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonesupporting

confidence: 78%

“…Indeed, it has been used successfully in the total synthesis of vioxanthin, 9 semivioxanthin, 10 cassiaside C 2 , 11 and kalafungin 12 and a racemic synthesis of thysanone dimethyl ether. 13 The dramatic effect of different substitution patterns on the tolyl anion on the yield of the annulation has been the subject of a recent study. 14 Scheme 2 Reagents and conditions: (i) 2-bromopropane, K 2 CO 3 , acetone, reflux, 16 h, 89%; (ii) LDA, THF, -78 °C to r.t, 30 min, 47%.…”

Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonementioning

confidence: 99%

“…1 H NMR (300 MHz, acetone-d 6 ): d = 1.30 (d, J = 6.5 Hz, 3 H, 3-Me), 2.11-2.17 (dd, J = 11.1, 18.8 Hz, 1 H, H ax -4), 2.73-2.66 (dd, J = 3.5, 19.4 Hz, 1 H, H eq -4), 4.30-4.36 (m, 1 H, H-3), 5.93 (s, 1 H, H-1), 6.62 (d, J = 2.3 Hz, 1 H, ArH), 7.07 (d, J = 2.3 Hz, 1 H, ArH), 9.73-10.31 (br s, 1 H, OH), 12.26 (s, 1 H, OH). 13 4,5…”

Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonementioning

confidence: 99%

“…), 2.62-2.67 (dt, J = 2.6, 18.6 Hz, 1 H, H eq -4), 3.60-3.65 (m, 1 H, H-3), 4.43-4.50 (dt, J = 3.4, 19.0 Hz, 1 H, H ax -1), 4.57-4.63 (m, 1 H, CHMe 2 ), 4.70-4.76 (m, 1 H, CHMe 2 ), 4.80-4.86 (dd, J = 2.0, 18.9 Hz, 1 H, H eq -1), 6.65 (d, J = 2.3 Hz, 1 H, ArH), 7.20 (d, J = 2.3 Hz, 1 H, ArH) 13. C NMR (100 MHz, CDCl 3 ): d = 21.2 (Me), 21.9 (2 × CHMe 2 ), 29.1 (CH 2 ), 63.8 (CH 2 ), 69.5 (CH), 70.7 (CH), 71.2 (CH), 104.9 (CH), = 60 (100) [M] + , 245 (10), 231 (22), 216 (60), 188 (30), 108 (22), 41 (45).…”

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An Efficient Enantioselective Synthesis of the 3C Protease Inhibitor (-)-Thysanone

Sperry¹,

Brimble²

2008

Synlett

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S y n t h e s i s o f t h e 3 C P r o t e a s e I n h i b i t o r ( -) -T h y s a n o n eAbstract: The enantioselective synthesis of the 3C protease inhibitor (-)-thysanone is described. The key step is the o-toluate anion addition to an a,b-unsaturated d-lactone. Spectroscopic analysis of the synthetic material confirms the 1R,3S stereochemistry of the natural product.Human rhinoviruses (HRVs) are the major cause of the common cold in the Western world and currently only symptomatic treatment is available to medicate rhinoviral infections. In addition to being attributed to the common cold, HRV infections are associated with acute and chronic bronchitis. 1 It is estimated the total economic impact of cold-related work loss exceeds $20 billion annually in the United States alone and the quest to discover efficacious therapeutic agents of HRV infections continues to be of major pharmaceutical interest. 1,2The pyranonaphthoquinone antibiotic 3 (-)-thysanone (1; Scheme 1) was discovered by chemists at Merck whilst screening fermentation broths of the fungus Thysanophora penicilloides aimed at identifying lead compounds that could be developed into chemotherapeutic agents for eventual control/cure of the common cold. 4 Thysanone was subsequently shown to be the first HRV-3C protease inhibitor identified by screening, possessing inhibitory activity with an IC 50 = 13 mg/mL, hence making it an ideal lead candidate for the design of therapeutic agents for treatment of the common cold. Scheme 1 Retrosynthetic analysis of (-)-thysanone 1Currently only one stereospecific synthesis of thysanone exists in the literature, a 16-step procedure commencing from (S)-propylene oxide. 5 This synthesis was instrumental in confirming the absolute stereochemistry of thysanone to be 1R,3S by detailed comparison with an authentic sample of the natural product, thus settling original doubts regarding the absolute configuration of the substituents on the pyran ring. 5 Our own synthetic efforts towards thysanone are longstanding 6 and most recently includes the asymmetric synthesis of deoxy analogues of 1 using a microwave-mediated enzymatic resolution as the key step. 7 We now report the enantioselective total synthesis of (-)-thysanone (1) using an o-toluate anion addition to an a,b-unsaturated d-lactone as the key step (Scheme 1).The addition of o-toluate anions to a,b-unsaturated d-lactones is not as widely used as the closely related HauserKraus annulation, 8 yet it provides a powerful route for the assembly of naphthopyran frameworks. Indeed, it has been used successfully in the total synthesis of vioxanthin, 9 semivioxanthin, 10 cassiaside C 2 , 11 and kalafungin 12 and a racemic synthesis of thysanone dimethyl ether. 13 The dramatic effect of different substitution patterns on the tolyl anion on the yield of the annulation has been the subject of a recent study. 14

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Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonesupporting

confidence: 78%

Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonementioning

confidence: 99%

Section: Scheme 1 Retrosynthetic Analysis Of (-)-Thysanonementioning

confidence: 99%

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An Efficient Enantioselective Synthesis of the 3C Protease Inhibitor (-)-Thysanone

Sperry¹,

Brimble²

2008

Synlett

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“…Moreover, the unpredictability of oxidative cleavage of olefins to aldehydes and the additive protection/deprotection for hydroxyl group in 20 put us in a dilemma. At this juncture, the reductive deoxygenation of lactol to benzopyran achieved by exposure to NaBH 4 [ 23 ] or triethylsilane (Et 3 SiH) [ 24 ] in the presence of TFA attracted our attention. Thus we could continue and complete the expected total synthesis of acortatarin A as illustrated in Scheme 6 .…”

Section: Resultsmentioning

confidence: 99%

Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

Cao

Sun

et al. 2014

Nat. Prod. Bioprospect.

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Graphical AbstractThe Acortatarin alkaloids exhibit a promising perspective against diabetic nephropathy and other ROS-linked diseases. Facile construction of the dioxaspirocycle motif was realized through tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols, which were derived in turn from convenient halomethylation of chiral lactones in natural carbohydrates pool.Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-014-0049-8) contains supplementary material, which is available to authorized users.

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Hauser–Kraus, Sammes, Staunton–Weinreb, and Tamura Annulations

Koning¹,

Georgiou²,

Michael³

et al. 2021

Organic Reactions

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This chapter provides a detailed survey of the Hauser–Kraus, Sammes, Staunton–Weinreb, and Tamura annulation reactions, as reported in the literature through March 2021. These reactions provide an efficient means for the synthesis of polycyclic aromatic compounds and related systems. The mechanism, scope, and limitations of each annulation reaction are covered, and typical methods for the preparation of the requisite starting materials (phthalides, homophthalic anhydrides, and related precursors) are provided. Applications of these annulation reactions as key steps in the synthesis of selected aromatic natural products are included, as are representative experimental procedures for accomplishing the annulation reactions.

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Simple and efficient synthesis of thysanone methyl ether

Cited by 16 publications

References 25 publications

An Efficient Enantioselective Synthesis of the 3C Protease Inhibitor (-)-Thysanone

An Efficient Enantioselective Synthesis of the 3C Protease Inhibitor (-)-Thysanone

Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

Hauser–Kraus, Sammes, Staunton–Weinreb, and Tamura Annulations

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