Let me add that aplysamine 6 is a natural product (of course) isolated from sponge Pseudoceratina sp.

Well, that’s not very complex target and the retrosynthesis and also total synthesis should be quite easy. My idea to disconnect this stuff is something like that:

Everything should by clear. All starting materials could be prepared from phenole or from commercialy avaiable anisaldehyde.

People who did the synthesis used very simmilar approach, so I didn’t draw retrosynthesis again. One important difference is use of Perkin condensation instead of something I labeled ‘Wittig-like’ reaction Let’s see how they completed whole total synthesis.

As you can see they started with p-anisaldehyde and they brominated it in first step. Ok, reaction is slow (there’s no Lewis acid), but more interesting is that aldehyde functional group isn’t oxidizied under such conditions. Coversion 3->4 is of course mentioned Perkin condensation (well, authors wrote that is Doebner-Knovenagel condensation… ok, probably it is ). Last step in this scheme is conversion of carboxylic acid to corresponding acyl chloride.

Now, second building block is prepared. They use p-hydroxy benzyl alcohol (can be obtained from p-anisaldehyde by its reduction) as second precursor. Next substitution oh hydroxyl group is performed to give 7. It’s a question why they didn’t convert -OH to better leaving group such as tosylate and so forth. 7 is reduced on palladium catalyst to amine hydrochloride 8, which in turn is brominated to 9 (again without any Lewis acid).

In next step two building blocks 5 and 9 are coupled and amide 10 is formed. OH group from aromatic ring of 9 isn’t acylated.

10 is a core of aplysamine 6. In next two steps primary amine moiety is attached to this structural core. This is achived by use of Williamson reaction (ether formation) with 1,3-dibromopropane to form derivative 11. 11 is converted to aplysamine 6 by well-known Sn2 reaction.

For more pieces of information please see:

N. Ullah, K. M. Arafeh, Tetrahedron Lett., 2009, 158-160.

Dideoxypetrosynol A is linear, polyacetylenic target molecule which consist 30 carbon atoms. It’s also C₂-symmetric molecule what is important to planning synthesis, of course. Let’s see structure of dideoxypetrosynol A:

It looks so simple but its spectrum of biological activities is very wide. Dideoxypetrosynol A was isolated from marine sponge (Petrosia sp.) found in Komun islands, Korea. It exhibit anticancer activity aganist ovarian and skin cancer cells. It can also inhibit DNA replication. So, biological properties are interesting but – unfortunately – concentration of dideoxypetrosynol in dry natural source is very poor (just about 23 mg in 14.5 kg dry source). Development of synthesis this target in larger scale is obvious.

There are also some compounds (with interesting biological activity) related to dideoxypetrosynol, for example: duryne 2, petrosynol 3:

Synthesis of such quite simple compounds shouldn’t be very complicated… maybe boring, but in fact – it’s not. Just look at retrosynthesis chart:

Benefits from presence of C₂ symmetry axis are clear. Grignard and Wittig key steps are obvious, but what is the ‘Oxidative coupling of Wittig reagent’? Let’s look at the synthesis to answer this question.

Synthesis starts with 4, TBS-protected terminal alkynol, which is deprotonated by butyllithium in first step and reacted with oxirane in the presence of Me3Al as Lewis acid to give diol 5. Now, free OH group is exchanged to Br and then, by adding triphenylphosphine, phosphonium salt 6 is formed. It’s quite clear. In next step buthyllithium is added again and in next few hours by acting of oxygen from the atmosphere – product 7 is forming. It’s oxidative coupling. Nice reaction.

Next steps are:

and they include deprotection and oxidation to form 8, Wittig olefination to form 9, and Grignard reagent addition to form racemic dideoxypetrosynol 1. Well, racemic.

Finally, racemic product was resolved by enzyme lipase AK:

There are also one feature in this synthesis: why don’t they start their synthesis from 1,4-dichlorobut-2-ene and undergo S_N2 reaction with Grignard reagent derived from corresponding alkyne? Well, actually they wanted to do it in such way but only side products were forming:

For more see:

B. W. Gung, A. O. Omollo, Eur. J. Org. Chem, 2008.