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Progesterone is very annoying to use because there are no good routes of administration that are both long lasting and efficient. Unlike estradiol, progesterone lack -OH groups so it cannot be esterified.

Progesterone has two =O moieties though, that are interesting, in the way that they can be modified into ethers, oximes or enol esters.

I want to focus on the last of the three.

The C3 end of progesterone is apparently very important for its progestogenic activity so it's better if we modify the other site, C20.

Enter progesterone C20 enol decanoate. I think this molecule is promising for a long-lasting, oil-soluble, progesterone depot injection. First, the decanoate chain makes it very highly liposoluble, which avoids Progesterone's low solubility problem. Second, the depot effect created by a long lipophylic ester chain makes cling tightly to the oil depot, making it diffuse to the rest of the body slowly, like estradiol/testosterone enanthate and undecylate/undecanoate. Third, once the molecule escapes the oil depot and enters the bloodstream, it is (should) rapidly hydrolyzed to Progesterone. Yes, bioidentical progesterone, not any progestin derivative. This allows it to be a systemic source of progresterone, allowing for not only nuclear progesterone receptors to be bound but also membrane progesterone receptors, the later less likely to be targets of other progestins.

This is where I need your help. The synthesis of progesterone C20 enol decanoate is probably quite easy, basically needing Progesterone and the fatty acid, i.e. decanoic acid, and the extra reagents to enolize the C20 site into a enol ester

Lab rats, chemists, hobby chemists, lab technicians, please respond and help develop this, which I think could be very useful. The answer to finally having a estradiol/progesterone combo injection or a long-lasting progesterone injectionj could be closer than we imagine.