Disconnected atoms

Disconnected atoms represent the simplest type of fragments. They are used to assess a chemical or biological property P in the framework of an additive scheme based on atomic contributions ... 

The essence of the problem is identification of the molecular fragment whether a connection of disconnected atoms or atomic groups, which can be viewed as critical in determining molecular activity. 

Avoid single disconnected atoms, especially generalized atoms ( any or hetero ) whenever possible. 

Disconnected structures in the molecule Individual parts of the compound are separated by a period. The period indicates that there is no connection between atoms or parts of a molecule. The arrangement of the parts is arbitrary. 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

The strategic bond is disconnected by just clicking with the mouse on it. A suitable synthesis precursor is then generated automatically by WODCA by adding appropriate atoms or groups to the open valences. 

You can see how the alkyl-lithium acts as tlie synthon CH3CH2 since the carbon-lithium bond breaks so that the electrons go with the carbon atom. Suggest a disconnection for TM 16. 

If one of the groups in the alcohol carbon atom is H, then another disconnection is ... 

Unfortunately this route gives only a 40% yield IJ. Amer. Cham. Soc 1951, 73, 3237) in the Grignard reaction, largely because benzyl Grignard reagents easily give radicals which polymerise. In any case, it s poor tactics to chop off carbon atoms one at a time, and a better disconnection would be ... 

One extra disconnection is all we need to cope with misaturated heterocycles. If a nitrogen atom is joined to a double bond in a ring, we have a cyclic enamine. This is made from an amine and a carbonyl compound in the same way as ordinary enamines ... 

A more general route to three-membered rings is based on a new type of disconnection the removal of an atom... 

Now disconnect any bond joining two common atoms and see if there is a good starting material. 

Because of the symmetry of TM 329 there are only two different disconnections of bonds between two common atoms. 

Analysis Marking the common atoms we find there are three possible disconnections of bonds between them, but only a or c give us simpler precursors. Both also are logical in that we can immediately write reagents for the synthons. 

Analysis Opening up the ring to see the true problem using our branch point guide we really want to disconnect the bond between the two ringed atoms so that strategy a (i), frame 340 is best. 

Using our strategic device of marking atoms common to more than one ring (see frames 329-333), we find there is only one disconnection of a bond joining two common atoms as the molecule is symmetrical ... 

Analysis We want to disconnect any of the bonds to the common atoms to give us a simple six-membered ring. We can best disconnect bond a as it is part of a 1,3-di oxygenated system ... 

Skeletal bonds directly to remote stereocenters or to stereocenters removed from functional groups by several atoms are preserved. Those between non-stereocenters or double bonds which lie on a path between stereocenters are strategic for disconnection, especially if that path has more than two members. 

Bonds along a path of 1, 2, or 3 C atoms between a pair of functional groups can be disconnected. 

Solvent disturbs chain deflection by interacting with it. At first, solvent molecules must be moved at chain deflection. In this case it may sufficiently decrease the distance between interacting atoms, which are closely disposed and valently disconnected. The model of a homogenous chain in solution is described [12]. The chain in the solvent possesses a higher observable local rigid-... 

Recognising the acetal in frontalin (3), a pheromone of the western pine beetle," is not so easy. Nevertheless, it is Important to look for the two oxygen atoms joined to the same carbon atom ( in 3a) and disconnect the acetal before considering any other steps. 

The cyanide route via bromide (16) back to bromide 17) would be one obvious method, but the alternative disconnection of two carbon atoms from (18) is shorter. 

Frontalin (18), the pheromone of the western pine beetle, is an acetal (atom has two single bonds to oxygen). Disconnection reveals diol ketone (19). 

The tosylatc must come from alcohol (44), Disconnection Lo an epoxide (45) is no good as the amine will attack the wrong atom. Change of oxidation level to (46) is more hopeful as the a-halo acid (47) is easily made. Another possibility is to use naturally occurring a 1 an ine ( 48),... 

The cis stereochemistry of (7) is irrelevant to (10 or (11), as cyclisation can give only ais fusion of two five-membered rings, but it might be a problem for (9). In any case, no disconnection, other than removing single carbon atoms, can easily be made on (9). Much the same is true of (12), but reconnection of the 1,6-dicarbonyl in (13) provides a good starting material (14). 

FGA and carbonyl strategy the synthesis of long chain fatty acids such as (16) can be achieved in a few steps by suitable FGA. Adding a carbonyl group in a 1,6 relationship allows reconnection to (17) and hence the disconnection of the six carbon atoms in the ring. Analysis... 

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