Total Synthesis of Papulacandin D

Denmark, Scott E.; Regens, Christopher S.; Kobayashi, T.

doi:10.1021/ja070071z

Cited by 126 publications

(69 citation statements)

References 36 publications

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“…Protection of the alcohol with TBSOTf ( 23a , 84%) followed by deprotection of PMB group with DDQ provided C21 alcohol 24a in 91% yield. The C1 methyl ester was then hydrolyzed by using KOH or TMSOK27 (which gave a better yield) to produce a seco -acid. The macrolactonization of the seco -acid using the Shiina reagent (2,6-methylnitrobenzoylanhydride)28 in toluene gave the crude protected macrolactone in 93% yield as a 60:40 mixture of the target (2 Z ,4 E )-dienyl lactone and its (2 E ,4 E )-isomer (not shown).…”

Section: Resultsmentioning

confidence: 99%

Streamlined Syntheses of (−)-Dictyostatin, 16-Desmethyl-25,26-dihydrodictyostatin, and 6-epi-16-Desmethyl-25,26-dihydrodictyostatin

et al. 2010

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The dictyostatins are a promising class of potential anticancer drugs because they are powerful microtubule stabilizing agents, but the complexity of their chemical structures is a severe impediment to their further development. Based on both synthetic and medicinal chemistry analyses, 25,26-dihydro-16-desmethyldictyostatin and its C6 epimer were chosen as potentially potent yet accessible dictyostatin analogs, and three new syntheses were developed. A relatively classical synthesis involving vinyllithium addition and macrocyclization gave way to a newer and more practical approach based on esterification and ring-closing metathesis reaction. Finally, aspects of these two approaches were combined to provide a third new synthesis based on esterification and Nozaki-Hiyama-Kishi reaction. This was used to prepare the target dihydro analogs and the natural product. All of the syntheses are streamlined because of their high convergence. The work provided several new analogs of dictyostatin including a truncated macrolactone and a C10 E-alkene, which were 400-fold and 50-fold less active than (−)-dictyostatin. In contrast, the targeted 25,26-dihydro-16-desmethyldictyostatin analogs retained almost complete activity in preliminary biological assays.

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Section: Resultsmentioning

confidence: 99%

Streamlined Syntheses of (−)-Dictyostatin, 16-Desmethyl-25,26-dihydrodictyostatin, and 6-epi-16-Desmethyl-25,26-dihydrodictyostatin

et al. 2010

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“…Further, iodination of (AE)-9 with N-iodosuccinimide in chloroform provided the aryl iodide (AE)-2 in 91% yield. 17 Subsequently, for construction of the 3,4-dihydroisocoumarin ring, we used palladium-catalyzed carbonylation of aryl iodide (AE)-2. It has been reported that acetoxy group serves as a good nucleophile compared to hydroxyl group in the lactonization Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

Total synthesis of racemic, natural (+) and unnatural (−) scorzocreticin

2014

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“…A similar epoxidation-spirocyclization method has been used recently by Denmark et al [142,143] in their synthesis of papulacandin D, as well as in an independent study [144] toward papulacandin analogues (Scheme 69).…”

Section: Scheme 63 Sharma Et Al's Dihma Approach Towards Dinemasone mentioning

confidence: 99%