diesters

[Sigmund Roid]

Let's say a steroid base has an extra hydroxy group, something like 1-hydroxytestosterone or 4-hydroxytestosterone. After esterification one will have a diester, so an ester on both the 1 (or 4) OH and the 17-OH. My question is, what will the half-life be? I can imagine that it is harder for the enzymes in the body to remove the first ester, since the second ester may express some steric hindrance (especially if it is a long ester). After the first ester is gone, the second ester will be removed with the same speed as a conventional monoester steroid. Also the solubility of the diester in oil will be better than a mono-ester, so it stays longer in the oily depot.

[spidey]

Actually, I don't know If I would expect much of a difference. Steric hindrence shouldn't really be a problem since the two esters are at opposite ends of the molecule.

More later. I am due at a meeting.

[spidey]

OK, I am back.

Another factor is a fundemental difference in the types of esters on the two positions.

If on the 4-position as in 4-hydroxytest, the 4-ester is an enol ester (think enol acetate Sigmund). This ester will be much more reactive than a normal ester as is on the 17-position. If you want, it is likely possible to remove the 4-ester in the presense of the 17-ester. Stirring in a mild acid solution would do the trick quickly.

If the ester is on the 1-position (no 1,2-double bond), then you have a beta keto-ester. These can be quite unstable/reactive. The 1-ester will eliminate easily to form a 1,2-double bond. In fact, it might be difficult to keep this from happening spontaniously in the presence of even mild acid or base. It may happen when it is formed in the presence of pyridine.

[anatole]

I agree, diesters will stay longer in the depot. Biologically speaking, I am not sure that serum esterases will make a difference between the two ester bonds

[Sigmund Roid]

I see, so it is very hard to esterify 1-hydroxytestosterone without affecting the 1-hydroxygroup..... so at the stage of the 1a,2a-epoxy, the test. should be esterified before going further. Good to know. BTW, I sent you an email a few mins. ago.

[spidey]

Thanks. I'll check it out. How far in time are you ahead of eastern standard time there in the Netherlands?