ORGN 741 |
| A mechanism of ring closure is considered. To make a large ring compound, two factors are required: the ring closure reaction, and a process bringing the two ends of the chain together. A random meeting of the two ends is less likely because of the large number of possible conformations since the entropy of activation is too unfavorable. If the molecule were to bend into the shape of a U, in order to reduce the hydrophobic interactions, then the two ends would be in close proximity. The hydrophobic effect may cause the first step to be a bilateral fold to avoid loose ends. Here, we propose an idea that the bottom of the U consists of one bond length, then the lengths of each arm would be just half of the ring size. It might be anticipated that whether each arm consists of an even number of atoms, or of an odd number, the sum would be an even number. This prediction was examined by analysis of the natural products literature. Even size 14-, 16-, and 18-membered rings are preferred compared to odd-membered rings and compared to ring systems greater than 19 atoms in size. The structural features of the majority of the compounds show an origin independent of a two-carbon (acetate) bioinsertion pathway and appear to bear no relationship to the odd-even frequency in natural fatty acids. Distribution of atom types (i.e., O, N, S heterocycles vs carbocycles) does not reveal a pattern to account for the odd-even preference. The effect of side-chain substituents or of heteroatom incorporation appears not to be a key factor in the even-over-odd preference. Finally, the macrocycle compounds exhibit an alternating pattern in contrast to analog linear natural products, which do not show the alternating pattern. |
|
Lipids, Nucleotides, Biosynthesis, and Mimetics
8:00 AM-12:00 PM, Thursday, 1 September 2005 Washington DC Convention Center -- 202B, Oral
Division of Organic Chemistry |