Total Synthesis of Rubriflordilactone B

Yang, Peng; Yao, Ming; Li, Jian; Li, Yong; Li, Ang

doi:10.1002/anie.201601915

Cited by 112 publications

(59 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 To our delight, we found that our DP4+ probability strongly s u g g e s t e d ( 9 2 . 6 % ) i s o m e r P R B 4 8 ( w i t h a 1R,5S,10R,16R,17S,20S,22S,23S configuration) as the most likely candidate, which was indeed the correct assignment (compound 2, Figure 1).…”

mentioning

confidence: 69%

See 1 more Smart Citation

Computational Chemistry Driven Solution to Rubriflordilactone B

2016

View full text Add to dashboard Cite

The structure of rubriflordilactone B (2) was determined by X-ray crystallography. However, the NMR data of the synthetic sample did not match those reported for 2. It was then suggested that the original sample contained an additional isomer of different solubility, pseudorubriflordilactone B (3), whose structure remained unknown. From theoretical calculations, reexamination of the NMR data, and biogenetic considerations, it is proposed that 3 should be the 16S,17R isomer of 2.T he Schisandraceae, comprising about 50 species of medicinally and economically relevant climbing plants belonging to the genera Katsura and Schisandra, are chiefly distributed in North America and the Southeast of Asia. Their phytochemistry has been recently reviewed, covering around 400 triterpenoids identified up to 2014. 1In 2006, Sun and co-workers reported the isolation of two highly unsaturated rearranged bisnortriterpenoids from Schisandra rubrif lora, designated as rubriflordilactones A (1) and B (2), Figure 1. These structures, featuring unique polysubstituted central aromatic rings, were respectively assigned to the novel compounds after detailed NMR spectroscopic analyses. Further, both proposed structures were confirmed by X-ray crystallography. 2Both natural products exhibited anti-HIV activity; the EC 50 of 2 against viral replication in HIV-1 IIIB -infected C8166 cells was 9.75 μg/mL. The latter also displayed low cytotoxicity against K562 cells.Two total syntheses of compound 1 have been reported so far, 3 whereas synthetic studies of the CDE, 5-epi-ABCDE, and DEFG ring fragments of 2 4 were crowned by its recent total synthesis, disclosed by Li and co-workers.5 Surprisingly, however, although the X-ray analysis of the synthesized structure 2 clearly confirmed its identity, its 1 H and 13 C NMR spectra were unlike those of the authentic product.Since the differences could not be attributed to solvent, temperature, concentration, or other usual factors, the authors hypothesized that the original sample of "rubriflordilactone B" may have contained two compounds with different solubility. The minor one crystallized, affording the reported X-ray structure which agrees with 2, whereas the major component, probably an isomer of 2, which was termed "pseudorubriflordilactone B", could be responsible for the observed bioactivities and published specific rotation and NMR spectroscopic data.Taking into account our interest in natural product characterization 6 using quantum chemical calculations of NMR shifts 7 and considering the remote possibility of unveiling the structure of pseudorubriflordilactone B (3) by reisolation of the natural product, we decided to examine the problem from a theoretical viewpoint. This approach has been employed in recent and resonant cases of structural misassignments, 8a−d providing useful insight in subtle issues beyond the limits of Xray methods as well. As most of the 13 C chemical shifts of isolated 3 were in close agreement with those found for synthetic compound 2 (except for δC15, vi...

show abstract

mentioning

confidence: 69%

“…5 Surprisingly, however, although the X-ray analysis of the synthesized structure 2 clearly confirmed its identity, its 1 H and 13 C NMR spectra were unlike those of the authentic product.…”

mentioning

confidence: 87%

Computational Chemistry Driven Solution to Rubriflordilactone B

2016

View full text Add to dashboard Cite

show abstract

“…417–422 Boasting polycyclic structures with a characteristic 7-membered ring and often containing multiple lactone moieties, these natural products are noted for both their structural intricacies and biological potencies – most have strong antiviral properties and many also display antiproliferative effects. 423,424 Rubriflordilactone B ( 352 ) itself is a bisnortriterpenoid (C-28) that contains a central tetrasubstituted aromatic ring.…”

Section: Syntheses From the 21st Centurymentioning

confidence: 99%

“…425 By anticipating the construction of that motif in at the end of their synthesis, Li and coworkers developed a convergent synthetic strategy involving the late-stage union of two complex building blocks. 422 Of note, a chiral pool terpene building block is not obviously identified within the gross structure of the final target.…”

Section: Syntheses From the 21st Centurymentioning

confidence: 99%

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

et al. 2017

View full text Add to dashboard Cite

The pool of abundant chiral terpene building blocks (i.e. “chiral pool terpenes”) has long served as a starting point for the chemical synthesis of complex natural products, including many terpenes themselves. As inexpensive and versatile starting materials, such compounds continue to influence modern synthetic chemistry. This review highlights 21st century terpene total syntheses which themselves use small, terpene-derived materials as building blocks. An outlook to the future of research in this area is highlighted as well.

show abstract

“…In addition, while rare, there have been cases of structural misassignments even with X-ray data available. 7,9 Typically, structural misassignment cases are detected once the synthesis of the originally proposed structure is achieved. Several review articles have been written in this regard during the last decade, highlighting the role of total synthesis to settle structural issues.…”

Section: Introductionmentioning

confidence: 99%

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

Della‐Felice¹,

Pilli²,

Sarotti³

2018

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Quantum chemical calculations of nuclear magnetic resonance (NMR) shifts and coupling constants have been extensively employed in recent years mainly to facilitate structural elucidation of organic molecules. When the results of such calculations are used to determine the most likely structure of a natural product in advance, guiding the subsequent synthetic work, the term "computer-guided synthesis" could be coined. This review article describes the most relevant examples from recent literature, highlighting the scope and limitations of this merged computational/experimental approach as well.

show abstract

Total Synthesis of Rubriflordilactone B

Cited by 112 publications

References 92 publications

Computational Chemistry Driven Solution to Rubriflordilactone B

Computational Chemistry Driven Solution to Rubriflordilactone B

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

Contact Info

Product

Resources

About