Retrosynthetic cuts

Tips The retrosynthetic cut in question is easy to recognize when one... 

Inasmuch as the starting materials are only vaguely dehned at this level of the planning process, one stops when the retrosynthetic cuts have yielded pieces of hve to eight skeletal atoms. Building blocks of that size are often commercially available or can be readily obtained by known literature procedures. 

Scheme 6.34 Trial and en or approach to identify an optimal retrosynthetic cut in a bridged polycycle...

Scheme 10.9 Retrosynthetic cuts at a stereogenic center to generate a chiral methyl branching...

Retrosynthetic cuts (ii)-(iv) in Scheme 10.9 relate to skeletal bonds, be it to R, or methyl. In these approaches the stereogenic center (= branch) is generated in a skeletal bond-forming step, which has to be executed in an enantioselective manner. Promising reactions are the alkylation of an Evans enolate [19], or the cuprate additions to enoates [20], as shown in Scheme 10.11 [21]. 

The following four different bonds in twistane (Scheme 6.60) are available for a retrosynthetic cut [25] (Scheme 13.27). 

The retrosynthetic analysis is performed in two steps in a first step, SYNGEN dissects the skeleton to find all fully convergent bondsets which utili2e starting material skeletons found in two successive levels of cuts. A bondset is a set of skeletal bonds that is cut during the retrosynthetic analysis or formed in any given synthesis. 

For the side-chain of retinol acetate, there are four options to cut the double bond system retrosyntheticaUy (Fig. 7.28). [55] Four double bonds give theoretically rise to 16 stereoisomers. Knowing that disubstituted (Z)-double bonds, as in jS-carotene, are isomerised under milder conditions than trisubstituted ones, limits the retrosynthetic choices. 

Hence, one normally focuses first on the molecular skeleton when planning a synthesis. Consider, for example callystatin A, a target molecule of medium complexity (Scheme 1.1). Try to identify building blocks from which this molecule could be assembled. To do this, one cuts the structure into smaller fragments using retrosynthetic disconnections. 

The two retrosynthetic schemes for callystatin A reveal significant differences. In Scheme A, the cuts are done to separate the target into pieces of roughly similar size. By contrast, in Scheme B, the cuts have been done at tbe periphery of the target structure thus failing to provide optimal retrosynthetic simplification. 

Moving ahead with this analysis, the retrosynthetic sword next cut the D-ring diketopiperazine ring of 6 (see Scheme 1) at the indicated amide linkage to reveal 7 as a protected amino acid precursor. Although the selection of a methyl ester and a 9-fluorenylmethyl carbamate (Fmoc) group to protect these new functionalities... 

Another method to synthesize hosts by formation of carbon-carbon bonds is the well known Eglinton alkyne coupling. Cutting the desired cage compound retrosynthetically into two half molecules the application of this method leads to short synthetic pathways with good yields. Therefore the oxidative alkyne coupline has become more and more important for the design of supramolecular host structures and led to the development of new variants of the... 

During this synthesis we have to make a new carbon-carbon bond. For our retrosynthetic analysis (going backwards) we cut this new bond with a squiggly line to make two pieces. As you will see on the next page, the challenge is to make these pieces and then make them bond them together. 

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