Bifunctional oxindole-chromone 4C building block directed asymmetric synthesis of bispirocyclic hexahydroxanthones featuring five contiguous stereocenters and two side-by-side oxindoles

2019 ◽  
Vol 6 (10) ◽  
pp. 1603-1607 ◽  
Author(s):  
Xiong-Li Liu ◽  
Yi Gong ◽  
Shuang Chen ◽  
Xiong Zuo ◽  
Zhen Yao ◽  
...  
Keyword(s):  
Small Molecules ◽  
Asymmetric Synthesis ◽  
Natural Product ◽  
Building Block ◽  
Three Dimensional ◽  
Optically Active ◽  
High Demand ◽  
Dimensional Complexity

Optically active small molecules based on privileged natural product frameworks and rich in three-dimensional complexity are in high demand.

Asymmetric Synthesis of 3,3′-Piperidinoyl Spirooxindoles and Discovery of Stereospecific Cycloadducts as Novel Hedgehog Pathway Modulators

Synthesis ◽  
2020 ◽  
Vol 52 (21) ◽  
pp. 3140-3152
Author(s):  
Kamal Kumar ◽  
Mohammad Rehan ◽  
Jana Flegel ◽  
Franziska Heitkamp ◽  
Jorgelina L. Pergomet ◽  
...  
Keyword(s):  
Transition Metal ◽  
Small Molecules ◽  
Asymmetric Synthesis ◽  
Natural Product ◽  
Transition Metal Complexes ◽  
Alder Reaction ◽  
Diels Alder ◽  
Hedgehog Pathway ◽  
Diels Alder Reaction ◽  
Efficient Access

An enantioselective hetero-Diels–Alder reaction of alkylidene­ oxindoles and 2-aza-3-silyloxy-1,3-butadienes, catalyzed by divalent transition metal complexes with N,N′-dioxide ligands offered an efficient access to natural-product-based 3,3′-piperidinoyl spiroox­indole class of small molecules. exo-Cycloadducts formed via stereospecific cycloaddition with Z-olefin displayed potent activity in modulation of hedgehog pathway.

Chemo-enzymatic synthesis of the C15–C23 unit of Leptomycin B

2002 ◽  
Vol 80 (6) ◽  
pp. 571-576 ◽  
Author(s):  
Michael Scheck ◽  
Herbert Waldmann
Keyword(s):  
Asymmetric Synthesis ◽  
Natural Product ◽  
Building Block ◽  
Enzymatic Synthesis ◽  
Aldol Reaction ◽  
Natural Product Synthesis ◽  
Leptomycin B ◽  
Enzymatic Transformation

The asymmetric synthesis of the C15–C23 unit of Leptomycin B (LMB) is described. All four stereocenters of the C15–C23 unit were prepared from one building block exhibiting only one stereocenter. This building block was synthesized via either an enzymatic transformation or starting from a chiral reagent.Key words: Leptomycin, natural product synthesis, enzymatic transformation, Aldol reaction, Pseudomonas fluorescence lipase (PFL).

The asymmetric synthesis of CF3-containing spiro[pyrrolidin-3,2′-oxindole] through the organocatalytic 1,3-dipolar cycloaddition reaction

2015 ◽  
Vol 51 (42) ◽  
pp. 8789-8792 ◽  
Author(s):  
Mingxia Ma ◽  
Yuanyuan Zhu ◽  
Quantao Sun ◽  
Xiaoyuan Li ◽  
Jinhuan Su ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Building Block ◽  
Cycloaddition Reaction ◽  
Optically Active ◽  
Dipolar Cycloaddition ◽  
New Strategy

A new strategy for the construction of optically active 5′-CF3 spiro[pyrrolidin-3,2′-oxindole] was described by using CF3CH2NH2 as a building block.

scholarly journals Toward the library generation of natural product-like polycyclic derivatives by stereocontrolled diversity-oriented synthesis

2005 ◽  
Vol 77 (1) ◽  
pp. 163-178 ◽  
Author(s):  
P. Arya ◽  
S. Quevillon ◽  
R. Joseph ◽  
C.-Q. Wei ◽  
Z. Gan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Natural Product ◽  
Small Molecule ◽  
Protein Interactions ◽  
Protein Function ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Complex Nature ◽  
Bioactive Natural Products ◽  
Small Molecule Libraries

Due to the growing interest in small molecules that could help in understanding protein–protein interactions based on signal transduction, the demand for the generation of small-molecule libraries that are inspired by bioactive natural products has grown significantly. Many of these pathways are highly complex and present tremendous challenges with the use of classical tools. A rapid access to natural product-like small molecules having structural complexity and diversity is crucial for systematically dissecting the functions of complex protein networking and understanding cell signaling pathways. The complex nature, the three-dimensional architecture, and the number of protein binding functional groups presented in three-dimensional arrays are some of the attractive features to incorporate in small-molecule chemical probes to be used as modulators of protein function.

Eumelanin-inspired core derived from vanillin: a new building block for organic semiconductors

2015 ◽  
Vol 51 (14) ◽  
pp. 2957-2959 ◽  
Author(s):  
Subhashini Selvaraju ◽  
K. A. Niradha Sachinthani ◽  
RaiAnna A. Hopson ◽  
Frederick M. McFarland ◽  
Song Guo ◽  
...  
Keyword(s):  
Small Molecules ◽  
Natural Product ◽  
Organic Semiconductors ◽  
Building Block ◽  
Cross Coupling

An eumelanin-inspired core derived from the natural product, vanillin (vanilla bean extract) was utilized for the synthesis of eumelanin-inspired small molecules and polymer via Sonogashira cross coupling.

A Free Energy Perturbation Approach to Estimate the Intrinsic Solubilities of Drug-like Small Molecules

2019 ◽  
Author(s):  
Sayan Mondal ◽  
Gary Tresadern ◽  
Jeremy Greenwood ◽  
Byungchan Kim ◽  
Joe Kaus ◽  
...  
Keyword(s):  
Solid State ◽  
Small Molecules ◽  
Three Dimensional ◽  
Aqueous Solubility ◽  
Computational Approach ◽  
Free Energy Perturbation ◽  
Perturbation Approach ◽  
Energy Perturbation ◽  
State Form ◽  
Good Agreement

<p>Optimizing the solubility of small molecules is important in a wide variety of contexts, including in drug discovery where the optimization of aqueous solubility is often crucial to achieve oral bioavailability. In such a context, solubility optimization cannot be successfully pursued by indiscriminate increases in polarity, which would likely reduce permeability and potency. Moreover, increasing polarity may not even improve solubility itself in many cases, if it stabilizes the solid-state form. Here we present a novel physics-based approach to predict the solubility of small molecules, that takes into account three-dimensional solid-state characteristics in addition to polarity. The calculated solubilities are in good agreement with experimental solubilities taken both from the literature as well as from several active pharmaceutical discovery projects. This computational approach enables strategies to optimize solubility by disrupting the three-dimensional solid-state packing of novel chemical matter, illustrated here for an active medicinal chemistry campaign.</p>

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