Side chain reorganization

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

The elaboration of the polyunsaturated side chain of asteltoxin requires a stereoselective coupling of aldehyde 2 with a suitable synthetic equivalent for the anion of 4-formyl-1,3-butadiene (see intermediate 3 in Scheme 4). Acid-induced skeletal reorganization of the aldehyde addition product, followed by an intermolecular... 

In the bilayer or upon interaction with detergent micelles, a structural reorganization of pardaxin aggregates takes place, in which the polar side chains interact with themselves and the hydrophobic residues are externally oriented in the pardaxin aggregate, therefore allowing interactions with the lipid backbone hydrocarbons. 

The use of polymeric coatings in catalysis is mainly restricted to the physical and sometimes chemical immobilization of molecular catalysts into the bulk polymer [166, 167]. The catalytic efficiency is often impaired by the local reorganization of polymer attached catalytic sites or the swelling/shrinking of the entire polymer matrix. This results in problems of restricted mass transport and consequently low efficiency of the polymer-supported catalysts. An alternative could be a defined polymer coating on a solid substrate with equally accessible catalytic sites attached to the polymer (side chain) and uniform behavior of the polymer layer upon changes in the environment, such as polymer brushes. 

Mechanistically, analogous to what already is suggested for 5-azido- or S-diazomethyl-1,2,3-triazoles (Section II,C), the participation of open-chain intermediates 287 or 288 is proposed (Scheme 46) the subsequent hetrocyclization engaging the pivotal sulfur and the azido or diazo-methyl side-chain develops into the rearranged 285 or 290, respectively. On the other hand, a concerted electronic reorganization involving the side-chain... 

Do not add new functional groups to side chains. The addition of a new group on a side chain can cause local reorganization of structure if the new group can make novel interactions. 

At this point, participation of the allyl side chain must 1 e recognized, because an n-butoxy derivative reacts in a different fashion. At least two routes, A and B, are open to pivotal intermediate IV (see Scheme 23.1). While the electron reorganization that leads to alkoxycarbene V (route A) and dihydro-furan (VII) via its addition to the terminal alkene would be justified by the high temperatures employed at which other carbenes have been thermally generated, the prior cyclization of zwitterion IX (route B) and its ensuing 1,2-hydrogen shift followed by C-C bond fragmentation in X—the natural precursor of products II and VII—would perhaps be more feasible. 

Finally, a fourth mechanism would be based on the fact that LTA may be bonded to both nitrogen and sulfur in XII with displacement of 2 moles of acetate from lead, to give XIV. The sulfonium sector would enhance the lability of its a carbon towards acetate, thus furnishing intermediate XV. This would secure the construction of the acetate-bearing side chain, while still holding the lead atom in a pincerlike structure. This molecule would be ideally suited ste-rically and electronically for the favorable six-electron electrocyclic process depicted in XV, This electron reorganization would yield product II directly. 

---