Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

Chen, Xiaoming; Zhang, Haijun; Lv, Houqiang; Shao, Xiaoru; Cheng, Tao; Wang, Huifei; Cheng, Bin; Li, Yun; Guo, Jingjing; Zhang, Jing; Zhai, Hongbin

doi:10.1002/ange.201709762

Cited by 24 publications

(9 citation statements)

References 67 publications

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“…The structural complexity and biological activities of calyciphylline A‐type alkaloids, which comprise a subfamily of Daphniphyllum alkaloids of around fifty members, have attracted the interest of synthetic researchers in the last sesquidecade. However, the only total syntheses achieved to date are of daphenylline, himalensine A, and longeracinphyllin A, all reported recently ( Figure ). …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

Jansana

Coussanes

Diaba

et al. 2019

Helvetica Chimica Acta

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A general procedure is reported for the synthesis of cis ring fused azapolycyclic compounds bearing an all‐carbon quaternary stereocenter at the ring fusion and an adequate functionalization for the assembly of new rings leading to advanced synthetic intermediates for Daphniphyllum alkaloid synthesis. The key carbon−carbon bond‐forming step in this approach is a radical cyclization of an N‐cycloalkenyl trichloroacetamide derivative involving a tetrasubstituted enamide to achieve polyfunctionalized lactams.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

Jansana

Coussanes

Diaba

et al. 2019

Helvetica Chimica Acta

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“…Aldol reaction is one of the most prominent reactions in the field of asymmetric synthesis due to its wide applications ranging from total synthesis of enantiomerically pure natural products to biologically active molecules . Work in the field got its first recognition in 1971 when proline was reported as an organocatalyst for intramolecular aldol transformation (Hajos‐Parris‐Eder‐Sauer‐Wiechert reaction) − and followed by a report on intermolecular aldol reaction .…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Direct Aldol Reaction in Confined Space: Molecular Conformations of Organocatalyst Affect Chiral Induction

et al. 2019

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We have demonstrated that chiral induction in the aldol product is possible by generating an enzyme‐like cavity in molecular framework of the amphiphlic catalyst. The esters of trans‐4‐hydroxy‐L‐proline and long chain fatty acids have been synthesized by O‐acylation. Synthesized molecules were used as organocatalysts for asymmetric direct aldol reaction between 4‐nitrobenzaldehyde and cyclohexanone. The molecular framework of the catalyst not only induces the amphiphilicity but also acquires specific conformation leads to formation of catalytic cavity facilitating stereo‐induction in the aldol product. Systematic addition of olefinic bonds in the long hydrocarbon chain makes this cavity more robust stabilizing transition state of the aldol product. By proper tuning of the water content and % loading of the catalyst in aldol reaction, o/w or w/o type emulsion is formed due to aggregation of catalyst molecules. Performance based evaluation of catalytic activity suggests that aldol reaction proceeds with ∼ 99% yield, 84% dr and 97.94% ee in presence of 10% catalyst (having three π bonds), in an o/w emulsion (85 equiv. of water) within 12 h. The stereoselectivity of the catalyst is almost maintained up to 2.5% loading. The high stereoselectivity of the aldol reaction is maintained even on increasing the amount of water to 300 equiv. A plausible reason has been proposed for retaining the high stereoselectivity and corroborated by computational analysis.

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“…[1,2] Thec ongested polycyclicr ing systems of these alkaloids,a long with their promising bioactivities,m ake them highly attractive synthetic targets. [1a,c,d, 3] Since the pioneering syntheses of several daphniphyllum alkaloids by the Heathcock group, [4] impressive total syntheses of various daphniphyllum alkaloids have been reported by the Carreira, [5] Smith, [6] Li, [7] Hanessian, [8] Fukuyama, [9] Zhai, [10] Dixon, [11] and Qiu groups. [12] Owing to the diversified architectures of daphniphyllum alkaloids,ageneral strategy for efficiently accessing these intriguing targets and determining their pharmaceutical potential would be desirable.B ya nalyzing the chemical skeleton of several daphniphyllum alkaloid subfamilies, including yuzurimine-type (for example,calycinine A), daphnilactone B-type (for example,c aldaphnidine C), calyciphylline A-type (for example,h imalensine A), and daphmanidin A-type (for example,d aphmanidin A) alkaloids,a6/7/5 tricyclic ring scaffold was recognized as the common structural feature (Figure 1).…”

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confidence: 99%

A Concise Total Synthesis of (−)‐Himalensine A

Chen

Guo

et al. 2019

Angew Chem Int Ed

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The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (−)‐himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu‐catalyzed nitrile hydration, a Heck reaction to construct the challenging 2‐azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot‐economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency.

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Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

Cited by 24 publications

References 67 publications

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

Asymmetric Direct Aldol Reaction in Confined Space: Molecular Conformations of Organocatalyst Affect Chiral Induction

A Concise Total Synthesis of (−)‐Himalensine A

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