Is it possible to make a beta-lactam with sulfur instead of oxygen? Do polysulfide medicines exist?

I haven't been able to find an example, but it is possible for sulfur to have a double bond with a carbon atom. Sulfur, in contrast to oxygen, tends to reduce rather than oxidize. Antioxidants are generally good. The more sulfur a molecule has, the greater chance it has of being an antioxidant. 

In order to replace the oxygen with sulfur in the beta-lactam ring, that sulfate group in the lower right would probably need to be replace with something smaller. 

Wikipedia says

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Compounds with double bonds between carbon and sulfur are relatively uncommon, but include the important compounds carbon disulfide, carbonyl sulfide, and thiophosgene. 

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On a side note, sulfur shows up in many retroviral drugs. 

If polysulfide compounds similar to polyketides exist, they could have medicinal use. Imagine if all the carbon-oxygen double bonds below were replaced with sulfur.

Polyketides, Immunosuppressants, Chemotherapy Drugs and Lipinski's Rule of Five

From Wikipedia:

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In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (>C=O, or its reduced forms) and methylene (>CH2) groups: [−C(=O)−CH2−]n.[1] First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. 

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Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical properties and physical properties that would likely make it an orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most orally administered drugs are relatively small and moderately lipophilic molecules.

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Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:

No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–hydrogen bonds)

No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)

A molecular mass less than 500 daltons

A calculated octanol-water partition coefficient (Clog P) that does not exceed 5

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In an attempt to improve the predictions of druglikeness, the rules have spawned many extensions, for example the Ghose filter:[10]

Partition coefficient log P in −0.4 to +5.6 range

Molar refractivity from 40 to 130

Molecular weight from 180 to 480

Number of atoms from 20 to 70 (includes H-bond donors [e.g. OHs and NHs] and H-bond acceptors [e.g. Ns and Os])

Veber's Rule further questions a 500 molecular weight cutoff. The polar surface area and the number of rotatable bonds has been found to better discriminate between compounds that are orally active and those that are not for a large data set of compounds.[11] In particular, compounds which meet only the two criteria of:

10 or fewer rotatable bonds and

Polar surface area no greater than 140 Å2

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Some other polyketides of note: paclitaxel, a chemo drug and discodermolide, a tumor inhibitor. 

What would be the effect of opening some of the rings on paclitaxel, aside from increasing its molecular weight? What about closing the partial rings in discodermolide?

In general, closing rings would mean fewer rotatable bonds.  

Ingenol mebutate - The Key to a Cure for HIV/AIDS?

From Wikipedia

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Ingenol mebutate has also been found to be useful for reactivating latent HIV virus in cells taken from individuals who have tested negative for signs of the disease following extended courses of anti-retroviral drugs, raising the possibility that this drug may be used to expose the last traces of virus, and thus potentially provide a permanent cure for HIV infection.

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It's intriguing how so many medicines have a heterocyclic core. Unlike most antibiotics, this one does not have a nitrogen atom as part of the ring. 

Comparison of Beta-lactams and Other Antibiotic Families

Compare the carbapenem above to the carbacephem and cephems below. Note the structure the heterocyclic cores. 

So we see that penicillins, cephalosphorins, and carbapenems all have a heterocyclic core with a beta-lactam ring. There are also beta-lactam antibiotics that have only beta-lactam at the core. An example is given below.

Below: a ureidopenicillin

In contrast, for bacteria with resistance to beta-lactam antibiotics, medicines like colistin must be used. Colistin is a member of the polymyxin family. 

It's interesting to note that beta-lactam antibiotics were derived from fungi and polymyxins came from gram-positive bacteria. This implies that a new class of antibiotics could be derived from gram-negative bacteria. Microorganisms wage constant chemical war on each other. 

Quinolones are another interesting group. Like the other antibiotics mentioned here, it too has a nitrogen ring. 

Aminoglycosides do not have nitrogen rings, but they do have nitrogen atoms with double bonds to carbon (an amino bond). 

All these antibiotics work by acting the cell walls of bacteria. Those walls come in two basic varieties shown below. Since both walls contain peptidoglycan, it seems the use of antibiotic from both beta-lactam and another family is necessary. The proper blend of antibiotics is at least an important question as discovering new ones. 

Indeed, triple antibiotic ointment contains a blend of aminoglycoside, a polymyxin, and a polypeptide antibiotics. 

Polypeptide antibiotics like bacitracin have high molecular weights.

Aldol Reactions and Polyketides for Pharmaceutical Synthesis

 

Synthesis Pathways for Various Medicines - a Continuing Project

I'm not sure how to organize this. If you know what you're looking for, control + f is your friend. 

 cephapirin

cefazaflur

cefroxadine

thiadazoles are important in pharmacology

cefonicid

ticarcillin

 

America's Football Player Presidents

I would like to state for the record that I have never been mistreated by a football player. In fact, I even played the game myself a few times. It didn't appeal to me. My paternal grandmother fell in love with my paternal grandfather while watching him play football in college, so there's that too. 

For some reason, every president since Nixon has either been a football player or posed as one.

The first was Gerald Ford, who played football in college.

I couldn't find a picture of Jimmy Carter playing football, but like most recent presidents, he threw out the ceremonial baseball pitch. He may have been an ex-president when the photo below was taken.

On to Reagan, who was a football player in a movies and real life.

 

Bush the Elder also posed with a prolate spheroid.

Bill Clinton had many football photo ops, though some did not paint him in the best light.

Bush Junior did not play football in college, but he was captain of the pep squad and dressed in drag as a cheerleader. He is fourth from the left in the photo below. 

The NYT article about it is amusing:

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ANDOVER, Mass. -- Perhaps there have been other presidential candidates who have dressed in drag, flaunting their legs from beneath a (fairly short) white skirt. But George W. Bush is probably the only one who has done it in front of a camera.

A photograph showing George and friends wearing wigs and employing falsies to fill out their sweaters appears in a yellowed copy of the school newspaper of Phillips Academy here in Andover, near Boston. It was 1963, and George, then a high school senior and head cheerleader, was leading a skit intended to mock rival schools.

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Obama did not play football in high school or college, but that did not stop him from posing as one. Over and over and over. 

Trump, on the other, rarely posed with a football. I consider that a point in his favor. The look of mild disdain on his face has a certain je ne sais quoi. 

And last, we have Biden, who by all accounts was an all-star football player in college.

Much like the US flag pin, it now seems mandatory for the president to pose with a football. Why is that? Seems like shameless pandering to me. 

Given the various catastrophes the US has been through since 1945, I'd prefer a president who was more interested in history or philosophy as a hobby. Is there ever going to be a president who will pose with a copy of The Federalist Papers? I'm not holding my breath. 

None of the great presidents, including all the ones on Mt Rushmore, were football players. Teddy Roosevelt threatened to ban the game if they couldn't reduce the injury rate. After that, all the pads and helmets became standard.  

Like the song says, it seems that high school really does never end.