chemistry

Spirorenone

Spirorenone is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Spirorenone rather than just read about it. In short: Spirorenone (INN; developmental code ZK-35973) is a steroidal antimineralocorticoid of the spirolactone group that was never marketed. Spirorenone possesses 5–8 times the antimineralocorticoid activity of spironolactone in animal studies.

Key takeaways

Spirorenone belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Spirorenone to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Spirorenone from memory before moving on to harder problems.

Reference excerpt

Spirorenone (INN; developmental code ZK-35973) is a steroidal antimineralocorticoid of the spirolactone group that was never marketed. Spirorenone possesses 5–8 times the antimineralocorticoid activity of spironolactone in animal studies. The initial discovery of spirorenone was deemed a great success, as no compound with greater antimineralocorticoid activity had been developed since spironolactone in 1957. Moreover, spirorenone itself has virtually no affinity for the androgen receptor while its progestogenic activity shows species differences, being somewhat greater than that of spironolactone in rabbits but absent in mice and rats. As such, it was characterized as a highly potent antimineralocorticoid with far fewer hormonal side effects relative to spironolactone. In clinical trials, spirorenone was found to be 4- to 10-fold as potent as spironolactone as an antimineralocorticoid, and is said to be the most active antimineralocorticoid identified to date. However, it was serendipitously and unexpectedly found that low doses of spirorenone lowered testosterone levels in men during clinical studies. This was determined to be due to metabolic conversion of spirorenone into drospirenone (1,2-dihydrospirorenone) by the enzyme Δ1-hydrase, a transformation that occurs only in monkeys and humans. Unlike spirorenone, drospirenone was found to be a highly potent progestin and antiandrogen in addition to antimineralocorticoid, with 8-fold the potency of spironolactone as an antimineralocorticoid and 0.3 times the potency of cyproterone acetate as an antiandrogen. Subsequently, investigation of spirorenone was discontinued and drospirenone was developed and eventually introduced instead as a contraceptive.

Synthesis

The 7-hydroxylation of 15,16β-cyclopropan-Androstenolone PC13075949 (1). Though this transformation has also been accomplished by chemical means, microbiological oxidation by Botryodiplodia malorum apparently proves superior to give PC44520204 (2). Acylation with pivalic anhydride proceeds selectively at the 3 hydroxyl group [82543-09-7] (). Epoxidation by means of tertiary butylhydroperoxide (tbhp) and Vanadyl acetylacetonate gives affords exclusively the β-epoxide [82544-13-6] (3). The remaining hydroxyl is then displaced by chlorine by means of triphenylphosphine and carbon tetrachloride, PC13075960 (4). Sequential reductive elimination followed by saponification gives the allylic alcohol [82543-15-5] (5). Reaction with the Simmons-Smith reagent affords the corresponding cyclopropane [82543-16-6] (6) the stereochemistry being determined by the adjacent hydroxyl group. Addition of the dianion from propargyl alcohol to the carbonyl group at position 17 adds the required carbon atoms for the future lactone [82543-17-7] (7). The alkyne bond is doubly reduced by catalytic hydrogenation [82543-18-8] (8). Pyridinium chlorochromate (PCC) mediated oxidation converts the primary alcohol to an acid while the secondary C3 alcohol is oxidized to a oxidized to a β-hydroxyketone (9). The carboxylic acid lactonizes to the gbl ring, while dehydration of the 5β-hydroxyl group leads to the conjugated enone (10). Dehydrogenation by means of DDQ introduces the C1=C2 olefin to afford spirorenone.

Illustrations

Worked examples

Example 1 — a first encounter with Spirorenone

Start with the simplest possible case. Write down what Spirorenone claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Spirorenone before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Spirorenone ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Spirorenone

In research: Spirorenone appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Spirorenone in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Spirorenone is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antimineralocorticoids, Cyclopropanes, Drugs not assigned an ATC code, so understanding it makes those chapters shorter.
In everyday life: Look for Spirorenone outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Spirorenone in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Spirorenone means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Spirorenone out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Spirorenone in simple terms?

Why does Spirorenone matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Spirorenone?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Spirorenone.