Retrosynthetic analysis disconnection approach

Substructure required for operation Reacting functionality Retron 

The terminology used in synthetic and retrosynthetic analysis is shown in Table 1.1. 

A transform in the case of the retrosynthetic counterpart of the Wittig reaction is shown below  

In a similar manner, the retrosynthetic analysis of the Diels-Alder reaction is represented below  

The retrosynthetic step involving the breaking of bond(s) to form two (or more) synthons is referred to as a disconnection. A synthon is an idealized fragment, usually a cation, anion or radical, resulting from a disconnection. One must select disconnections which correspond to the high yielding reactions. 

---

To recognize the different levels of representation of biochemical reactions To understand metabolic reaction networks To know the principles of retrosynthetic analysis To understand the disconnection approach To become familiar with synthesis design systems... 

In contrast to Nicolaou s synthetic plan, the retrosynthetic analysis of Holton s approach preserves the non-synthetically significant B ring and proceeds through disconnection of bonds which are involved in the D and C rings, to arrive finally to the bicyclo[5.3.1]undecane derivative 32, as the starting material. 

This reaction is used as one step [(7) to (6)] of the multistage synthesis of the monocyclic sesquiterpenic hydrocarbon, dehydro-a-curumene (3) [6-methyl-2-(4-methylphenyl)hepta-l,5-diene].247 The overall strategy is revealed from a retrosynthetic analysis for this compound, and is of interest since it emphasises the logic of the disconnection approach and draws together a number of important reactions which are relevant to this discussion of unsaturated compounds. 

This time-honoured view of ring construction preceded the retrosynthetic approach it is still of value since it provides an indication of which bonds could be selected for disconnection. The more rigorous application of the principles of retrosynthetic analysis leads of course to the formulation of synthons and their reagent equivalents. 

The disconnection or synthon approach now integrated into the text, and the principles of retrosynthetic analysis applied to relevant aliphatic, aromatic, alieyelic and heterocyclic compounds. 

The synthetic pathway for a drug or analogue must start with readily available materials and convert them by a series of inexpensive reactions into the target compound. There are no obvious routes as each compound will present a different challenge. The usual approach is to work back from the target structure in a series of steps until cheap commercially available materials are found. This approach is formalized by a method developed by S Warren, which is known as either the disconnection approach or retrosynthetic analysis. In all cases the final pathway should contain a minimum of stages, in order to keep costs to a minimum and overall yields to a maximum. 

The three variations of the retrosynthetic analysis of quadrone discussed in the preceding section were based upon one general concept the sequential bond-after-bond disconnection of the core of the target molecule into a set of smaller fragments. Logistically it is an absolutely reliable approach a consistent... 

The following discussion on retrosynthetic analysis covers topics similar to those in Warren s Organic Synthesis The Disconnection Approach and Willis and Will s Organic Synthesis. For an advanced treatment of the subject matter, see Corey and Cheng s The Logic of Chemical Synthesis. 

With this new approach in mind, the revised retrosynthetic analysis would utilize two different Wittig reactions to homologate the carbon side chains, providing ketoolefm (+)-16 (Scheme 13). Further disconnection revealed hydroxy aldehyde (+)-27 which could arise from a selective DIBALH reaction of lactone (+)-28. Applying Bringmann s method, lactone (+)-28 would be enantiomerically enriched via a kinetic resolution of a racemic lactone mixture. Racemic lactone ( )-28 could arise from a... 

Snider published the synthesis of desmethylamino FR901483 in 1998 [9] and one year later, the first total synthesis of natural (-)-FR901483 [2]. The disconnective analysis is outlined in Scheme 5. The key step in the retrosynthetic analysis is the disassembly of the azatricyclic structure of 1 by a retro-aldol process, which leads to aldehyde 6. In the forward sense, while this approach should provide efficient access to the ring system,... 

Structural similarities between these oxazole containing 23-membered polyunsaturated macrocyclic lactones led to similar disconnection approaches providing entry to all members of this family of antibiotics. A retrosynthetic analysis for the synthesis of pristinamycin Ilg (virginiamycin M2) (34), griseo-viridin (35) and madumycin II (37) is depicted in Scheme 8 from which the key precursors (38), (39), (40), (41) and (42) have been identified for formation of the macrocycle [94, 95, 96]. 

One approach to retrosynthetic analysis is to consider a retrosynthetic step as a disconnection of one of the bonds (Section 7.15). ... 

The first problem will prepare 4-bromoaniline (168) from benzene. Syntheses that transform one aromatic compound into another aromatic compound, such as this one, do not lend themselves to the retrosynthetic analysis approach presented in Chapter 25. Most of these syntheses involve functional group transformations. For the sake of continuity, a retrosynthesis is shown in which the amino group is removed to generate bromobenzene, which is obtained directly from benzene. The NH2 unit probably comes from reduction of a nitro group (Section 21.6.2), so the first precursor is 4-bromonitrobenzene (59) and disconnection of the C-N bond leads to the preparation of 59 by reaction of bromobenzene (35) with nitric acid/sulfuric acid. Bromobenzene is prepared directly from benzene as shown in the illustration. 

---