Retrosynthetic plan

The category of 2-Gp-keyed transforms which disconnect C-C bonds is among the most important of all transform types. These transforms, especially in their stereoselective versions, are workhorses of retrosynthetic planning as their names alone attest aldol, Michael, Claisen,... 

Atractyligenin and its sulfated glucoside (actractyloside) are toxins which block the transport of ADP into mitochondria and which occur in the coffee bean. Atractyligenin was synthesized following a multistrategic retrosynthetic plan in which the disconnection of ring B was a major objective. Novel stereocontrolled processes were employed for the critical cyclization to form the tetracarbocyclic network and for introduction of the carboxylic substituent. 

Part Two, a collection of multistep syntheses accomplished over a period of more than three decades by the Corey group, provides much integrated information on synthetic methods and pathways for the construction of interesting target molecules. These syntheses are the result of synthetic planning which was based on the general principles summarized in Part One. Thus, Part Two serves to supplement Part One with emphasis on the methods and reactions of synthesis and also on specific examples of retrosynthetically planned syntheses. 

In this section, we consider several syntheses of six illustrative compounds. We examine the retrosynthetic plans and discuss crucial bond-forming steps and the means of stereochemical control. In this discussion, we have the benefit of hindsight in being able to look at successfully completed syntheses. This retrospective analysis can serve to illustrate the issues that arise in planning a synthesis and provide examples of solutions that have been developed. The individual syntheses also provide many examples of the synthetic transformations presented in the previous chapters and of the use of protective groups in the synthesis of complex molecules. The syntheses shown... 

The synthesis in Scheme 13.5 also makes use of an aromatic starting material and follows a retrosynthetic plan similar to that in Scheme 13.3. The starting material was 4-methoxybenzaldehyde. This synthesis was somewhat more convergent in that the entire side chain except for C(14) was introduced as a single unit by a mixed aldol condensation in step A. The C(14) methyl was introduced by a copper-catalyzed conjugate addition in Step B. 

The first (+)-discodermolide synthesis was completed by Stuart Schreiber s group at Harvard University and is outlined in Scheme 13.68. This synthesis was carried through for both enantiomers and established the absolute configuration of the natural material. The retrosynthetic plan outlined in Scheme 13.67 emphasizes the stereochemical triads found at C(2)-C(4), C(10)-C(12) and C(18)-C(20) and was designed to use a common chiral starting material. Each of the segments contains one of the stereochemical triads. 

A related IMDA key step, however with exo geometry, was apphed in Mulzer s synthesis of ehsabethin A (22) [32]. According to the retrosynthetic plan (Scheme 14) the elisabethane carbon skeleton would be assembled via an IMDA cychzation of quinone 86 which would be generated by oxidation of the corresponding hydroquinoid precursor. Selective hydrogenation, base-catalyzed... 

Rather recently, Curran has published an important account of radical reactions and retrosynthetic planning [29], in which he introduces a convenient symbolism in order to incorporate radical reactions into standard retrosynthetic analysis. 

The synthesis in Scheme 13.5 also makes use of an aromatic starting material and follows a retrosynthetic plan corresponding to that in Scheme 13.3. This synthesis is... 

By bond polarity and resonance, the carbonyl carbon and a carbon (i to the carbonyl carbon can be utilized as electrophilic centers—die carbonyl group by direct nucleophilic addition and die /3 carbon by Michael addition to an a,/3-unsaturated ketone. By resonance interaction, the a position in carbonyl compounds and y positions in o, /3-unsaturated carbonyl compounds can be converted to nucleophilic centers by proton removal. These normal polarities are used frequently in retrosynthetic planning as points of disconnection to establish potential bond-forming steps using carbonyl groups. 

Scheme 7.1 Carreira s retrosynthetic plan for the synthesis of (+ )-zaragozig acid C.

Good retrosynthetic planning for ( + )-neocarzinostatin would also make every effort to identify nine-membered carbocycle precursors that were considerably less strained. Such molecules should be far easier to... 

Sound strategic planning would also attempt to pinpoint those features, already present in the epoxydienediyne core, which could greatly assist in assembly of the nine-membered carbocycle. Clearly, such structural elements would have to be retained in any prospective cycli-sation precursor. With these things in mind, we will now examine Myers retrosynthetic plan for this target. 

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