Could Isomerization of Alkaloids in Common Black Pepper (Piper nigrum) Provide New Leads for Pharmaceuticals?

in #sciencelast year (edited)

In one of my past lives I was a medicinal organic chemist using natural products from plants to discover new drugs and formulations. Sadly, the trend in the pharmaceutical industry has been away from unpatentable natural drugs to more profitable synthetic compounds.

My philosophy today is the antithesis of that particular past life: As a senior citizen I am convinced that exercise, nutrition and minimal medications, with selective natural remedies where appropriate, are the best course for one's healthcare.

Still, I Can't Help but Think About Molecules

Black Pepper, a.k.a. "The King of Spices" has been prized for centuries (Wikipedia) as a condiment and medicine. I eat larger amounts of ground pepper and raw peppercorns than the average American, I'm sure.

Recently I was reading a 2016 paper by Gorgani et. al. discussing a review of the chemical properties and medicinal uses of piperine, the active principal in black pepper responsible for its pungency.

Piperine, isopiperine, chavicine, isochavicine, and other similar compounds are known to occur in black pepper, and their medicinal and culinary values are ancient knowledge.

IMG_1768.PNG

Main alkaloids from Piper nigrum

IMG_1769.JPG

Other alkaloids from Piper nigrum

I remember isolating piperine from pepper by extraction with chloroform as one of my class experiments learning to isolate natural products.

Isochavicine May be a Lead

If you look at isochavicine with rotated 3,4 (beta, gamma) bonds, at least two interesting conformations become apparent:

IMG_1770.PNG
IMG_1781.PNG

diagram by @qiyi

These configurations (above) would hypothetically be extremely prone to spontaneously undergo sigmatropic Diels Alder cyclization and aromatization (source) to form two possible alpha(1)-napthoyl-piperidine amide derivatives (below):

IMG_1771.PNG
IMG_1782.PNG

diagram by @qiyi

Diels-Alder cyclization or other photocatalytic conversions could occur in vivo after absorption and within skin cells exposed to sunlight (Wikipedia).

Biological Activity?

It is likely some type of biological activity of medicinal advantage could be derived from these compounds. The conjugated double bonds between a carbonyl and an aromatic group could undergo a wide range of reactions to create derivatives.

The cis, cis isomer, chavicine, is sterically hindered from adopting these conformations due to the planar arrangement of conjugated double bonds, but synthetic analogs might be possible.

Such derivatives are not known to occur in nature, so they could be patented. Furthermore they are conformational isomers of naturally-occurring biologically active compounds with potential for further investigation.

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Great article! I was just in Costa Rica where I visited a spice plantation growing black pepper, vanilla, cacao and other spices organically.

I'll put that on my bucket list! I remember Baltimore Harbor where the McCormick Spice Co. had it's port, you could smell the aromas.

Short but deep article. I also worked in "my past life" with various natural products. It's a strange passion.

I don't want cars, boats, or golf equipment...I need a lab (or computer and platform) to use my skills.

Me too. Lab all the way and I am building one. I will share my notes sir!

I've designed and started several labs and programs. I look forward to your posts.

Love the post, I consume a hell of a lot of black pepper freshly ground as well but never raw, I would be interested in trying it! I use it in combination with turmeric since the black pepper compounds increase the potency of the turmeric. You’re not the only one who uses it so much around here! ;)

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Wow, thanks!

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Thank you!

Great read! Love the high-quality science-based natural product content. Pepper is definitely a spice that we could not live without. We just gave you a small upvote together with our many followers of the @nunesso blog. Have you heard of @nunesso? If you write more content like this be sure to use the #nunesso or #naturalproducts tag. We are looking to reward authors and content creators who produce exceptional natural product-related articles to give upvotes, resteems and be featured in our curation posts!

Thanks for making me aware of your tag and blog. I find interesting info and will follow for more.