Naturalproductman’s Blog

Hey, is that a natural product?!

Eudistidine A

Posted by naturalproductman on April 20, 2015

The NCI does some nice work with natural products. Kirk Gustafson and co-workers at Bethesda have reported in JACS on some new natural products that block the interaction between p300 and HIF1alpha.

70

JACS paper

Posted in Alkaloids, Protein-Protein Interaction, Proteins, Total Synthesis | Leave a Comment »

Ethanol + Tylenol = Carcinogen

Posted by naturalproductman on April 19, 2015

I thought it would be fun to talk about ethanol today. Structurally, ethanol is an interesting natural product because it is water but you just put an ethyl substituent on the oxygen. Ethanol’s boiling point is 78 degrees celsius – thus lowering the boiling point from water when a hydrogen bond donor is lost. Biosynthetically, ethanol comes from the 2 electron reduction of acetaldehyde, which is derived from the decarboxylation of pyruvate and pyruvate is a product of a 10-step breakdown of glucose (two moles of pyruvate from one mole of glucose).

Ethanol actually induces the expression of cytochrome P450 2E1 in our bodies, the enzyme which oxidizes ethanol to acetaldehyde then to acetic acid (vinegar?!). It must be our body’s way of removing ethanol, this interesting signalling molecule found to have many other interesting effects in our brain.

So it is the link between the two components (1. ethanol and 2. increased cytochrome P450 2E1 expression), which brings up the point: when drinking alcohol, don’t take Tylenol, which is also a substrate for cytochrome P450 2E1. Tylenol (also known as acetaminophen), is N-acetyl-para-amino-phenol. So it’s a phenolic compound which can become oxidized to the quinone by electron transfer to the iron center of P450 2E1. This reactive electrophilic quinone (also known as N-acetyl-para-benzoquinone imine or NAPQI) can form DNA adducts and mutation during DNA replication, leading to cancer. The antidote for NAPQI over exposure is N-acetylcysteine, which reacts with NAPQI in the same nucleophilic manner that DNA adducts to NAPQI. Except that a sulfur nucleophile from N-acetyl-cysteine is much better than the aza-nucleophile from any of the DNA bases. Not only does NAPQI introduce  mutations in our genome, NAPQI depletes glutathione, an important antioxidant in our bodies.

Posted in Toxicology | Leave a Comment »

Steenkrotin A synthesis

Posted by naturalproductman on April 18, 2015

Huanfeng Ding and co-workers from Zhejiang University have reported in ACIE on the synthesis of steenkrotin A.

steenkrotin A

ACIE paper

Posted in Diterpenoids, Methodology, Radical Chemistry, Total Synthesis | Leave a Comment »

Ouabagenin synthesis

Posted by naturalproductman on April 17, 2015

Masayuki Inoue and co-workers from the University of Tokyo have reported in Chemical Science on the synthesis of ouabagenin.

 
ouabagenin
Chemical Science paper

Posted in Steroids, Total Synthesis | Leave a Comment »

Nitriles to amides

Posted by naturalproductman on April 16, 2015

This may be a good alternative to the Ghaffar-Parkins catalyst. Jyotirmayee Dash and co-workers at Indian Association for the Cultivation of Science have reported in JOC on using potassium tert-butoxide to convert nitriles to amides.

amide

JOC paper

Posted in Methodology | 1 Comment »

Reverse Claisen cascade

Posted by naturalproductman on April 16, 2015

Yongjia Shang and co-workers from Anhui Normal University have reported in JOC on an interesting iron catalyzed cascade reaction.

JOC paper

Posted in Cascade Reactions, Claisen rearrangement, Iron, Methodology, Sigmatropic Rearrangements, Transition Metal | Leave a Comment »

Surprisingly deshielded proton

Posted by naturalproductman on April 16, 2015

Normally when you see a benzylic proton, you might think of the chemical shift between 2-3 ppm, and when you think of a proton alpha to a hetero atom such as that of an amide, you might think of a chemical shift in the range of 3-4 ppm, but this example here shows the chemical shift of the combination of a benzylic proton that is also alpha to an amide to be 6.0 ppm. The JOC paper was published by Fernando Sartillo-Piscil and co-workers at Universidad Autónoma de Puebla, México.

Interesting.

JOC paper

Posted in Methodology | Leave a Comment »

Mn catalyzed C-H azidation

Posted by naturalproductman on April 16, 2015

Jay Groves and co-workers have reported in JACS on a Mn-catalyzed C-H azidation reaction.

Mn

JACS paper

Posted in C-H activation, Manganese, Methodology, Transition Metal | Leave a Comment »

Pd-catalyzed DKR

Posted by naturalproductman on April 16, 2015

Xinjun Luan and co-workers have reported in JACS on a palladium catalyzed dynamic kinetic resolution of biaryls to spirocyclic centers.

spirocycle

JACS paper

Posted in Cascade Reactions, Kinetic resolution, Methodology, Palladium, Transition Metal | Leave a Comment »

A Formal Metathesis

Posted by naturalproductman on April 16, 2015

Zhang Jie-Shi and co-workers from the Chinese Academy of Sciences have reported in JACS on a rhodium catalyzed exchange between an aryl keton and an aryl carboxylic acid to form aliphatic carboxylic acids and biaryl compounds.

cascade

JACS paper

Posted in Cascade Reactions, Metathesis, Methodology, Rhodium, Transition Metal | Leave a Comment »

 
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