Genome complexity; Tour's synthesis problem (Introduction)

by David Turell , Monday, March 04, 2019, 18:58 (2090 days ago) @ David Turell

Tour is a world-famous organic chemist who has stated how hard it is to make functional organic molecules:

David: James Tour: " We synthetic chemists should state the obvious. The appearance of life on earth is a mystery. We are nowhere near solving this problem. The proposals offered thus far to explain life’s origin make no scientific sense.”

dhw: Ditto the mysteries of consciousness and speciation. Great article, which should be compulsory reading for all theists and atheists!

DAVID: Dr. Tour is in Houston at Rice University. He is a Jewish believer.

dhw: No problem, so long as he acknowledges that his own explanation of life’s origin makes no scientific sense either. I don’t object to faith. I object to people who have faith in God or in chance denigrating one another’s faith and pretending they know better.

David: The difficulty in making organic molecules by human effort compared to living processes ease in doing it is his main point.

https://www.chemistryworld.com/news/the-five-reactions-on-every-organic-chemists-wish-l...

This article describes the problem for human chemists who cannot imitate what life easily produces:

" Why do so many drugs have structural similarities? If you look at many of the best-selling and most-prescribed medicines – like hepatitis C treatment sofosbuvir, antihypertensive lisinopril or asthma drug fluticasone – they have a few things in common: they are densely functionalised, have at least one ring and some unprotected amines or alcohols, and often a scattering of fluorine atoms.

"Part of the answer is that drug discovery chemists are limited to a chemical space that can be accessed by known reactions and the available building blocks. They also need to consider biology, so reactions that tolerate basic nitrogen atoms are a must since they feature in almost every single biologically active compound. Reactions using only off-the-shelf reagents that don’t catch fire when they’re exposed to air are also a big plus as there’s often no easy access to specialist equipment like glove boxes.

"A 2014 analysis1 showed that only two reactions make up over half of all those used in synthesis to discover and develop drugs: the amide formation and the Suzuki–Miyaura cross coupling. ‘The reason these have contributed so much to medicinal chemistry is that they are the most robust reactions,’ says György Keserű, who leads a medicinal chemistry group at the Hungarian Academy of Sciences.

***

" every medicinal chemist has a list of reactions they wished existed. Here’s what this list might look like.

"1. Fluorination – Exchanging a specific hydrogen for a fluorine atom in molecules with many functional groups. A reaction that installs a difluoromethyl group would be nice too.

"2. Heteroatom alkylation – A reaction that – selectively – attaches an alkyl group onto one heteroatom in rings that have several, such as pyrazoles, triazoles and pyridones.

"3. Carbon coupling – A reaction as robust and versatile as traditional cross coupling for stitching together aliphatic carbon atoms – ideally with control of chirality, too. Chemists also want more options for the kinds of molecules they can use as coupling precursors.

"4. Making and modifying heterocycles – A reaction to install functional groups – from alkyl to halogen – anywhere on aromatic and aliphatic heterocycles, such as pyridine, piperidine or isoxazole. Reactions that can make completely new heterocycles from scratch would be a bonus.

"5. Atom swapping – A reaction that can exchange individual atoms selectively, like swapping a carbon for a nitrogen atom in a ring. This chemical version of gene editing could revolutionise drug discovery, but is probably furthest from realisation."

Comment: The article discusses each wish describing the complex problems, but the point is made. The organic chemistry of living organisms is far beyond what bright designing humans can achieve. Yet atheists claim nature figured it all out naturally. No chance!