Retrosynthetic scheme

On the basis of the preceding discussion the reader should be able to derive retrosynthetic schemes for the construction of targets 6, 7, and 8 based on the Diels-Alder transform. 

These strategies guide the retrosynthetic conversion of 272 to 278 and the further conversion of 278 via 279 to 282. The r-butyl substituent actuates the clearability of the stereocenters in 279. Further retrosynthetic simplification as dictated by basic FG-, stereochemical and topological strategies then leads from 280 to 281 and to 282, a previously described substance. The successful synthesis followed closely the above outlined retrosynthetic scheme. An enantioselective process was devised for the synthesis of 281 from 282 (see Section 10.12).67, 83... 

Samuel Danishefsky s group at the Sloan Kettering Institute for Cancer Research in New York has also been active in the synthesis of the natural epothilones and biologically active analogs. One of their syntheses also used the olefin metathesis reaction (not shown). The synthesis in Scheme 13.62 used an alternative approach to create the macrocycle, as indicated in the retrosynthetic scheme. The stereochemistry at C(6), C(7), and C(8) was established by a TiCl4-mediated cyclocondensation (Step A). The thiazole-containing side chain was created by reaction sequences F and G. The... 

Use retrosynthetic analysis to suggest syntheses of the following compounds. Develop at least three outline schemes. Discuss the relative merits of the schemes and develop a fully elaborated synthetic plan for the most promising retrosynthetic scheme. 

Suppose for simplicity to refer to nojirimicin as target, in a retrosynthetic scheme the nitrogen (-NH2 or -N3) can be inserted alternatively in position 1 or in position 5, whereas the other position must be electrophilic (represented as synthon with a carbocation) (Fig. 33). 

Fig. 33 General retrosynthetic scheme for imino sugars synthesis.

Fig. 4.2.7. Retrosynthetic scheme explored for the preparation of SPC (taken from Ref.

I didn t think that radical chemistry could be so mild and selective, is the nicer version of comments one often hears after seminars. What is the underlying reason for the misconception Probably that radical transformations often seem counterintuitive to those brought up with classical retrosynthetic schemes. As a result, the use of radicals is considered by many synthetic chemists as a last resort only to be used when other more traditional methods have failed. Additionally, radical reactions are usually regarded as being unselective and involving toxic reagents. 

In practice, the synthesis of compound 13 was carried out according to Scheme 4.15, in which the "dibromocarbene" was substituted for "methylene" in order to exert better control of the reaction and thus giving the monoadduct as the predominant reaction product [31]. Although this meant an extra step in the synthetic sequence, the great selectivity and the excellent yields obtained compensated this "deviation" from the original retrosynthetic scheme. 

A practically identical retrosynthetic scheme was also worked out by Corey [33] for the synthesis of helminthosporal (36) a polycyclic natural product with somewhat greater structural complexity than compound 33. 

In practice the derived retrosynthetic scheme must be modified and optimised in order to introduce the pertinent control elements (protecting groups, activating groups, etc.) and to direct the synthesis along the planned pathway. 

In fact a 1,4-dissonant system may be also reconnected to a dissonant 5-membered heterocycle. This solution is also valid when the heterocycle is an easily available starting material such as furan or furfural. For instance, syntheses of cis-jasmone (3) have been reported which follow retrosynthetic schemes shown in Scheme 5.24 [27] ... 

In practice, the synthesis was carried out as outlined in the retrosynthetic Scheme 13.2.8. The Diels-Alder reaction between butadiene and (+)-(/ )-5-methyl-2-cyclohexenone (31), in the presence of SnCl in anhydrous acetonitrile solution at... 

The synthesis is outlined in Scheme 13.4.2, in which the numbering of the synthetic intermediates parallels that of the retrosynthetic scheme. 

In organic synthesis design, like in chess, it can also be interesting to outline some medium- or long-term intermediate "target molecules". We can perharps perform disconnections to obtain certain intermediates, whose structure is appropriate in order to apply transforms of special interest. If this transform represents a reaction that affords the basic skeleton of the target molecule, probably we have attained an excellent retrosynthetic scheme. 

We devised a de novo-synthesis approach to this class of compounds based on the inverse-type hetero-Diels-Alder methodology, which is exhibited in the retrosynthetic Scheme 11. 

The various published syntheses of tetramic acids and their derivatives may be divided into two basic methods, according to the retrosynthetic scheme (Scheme I). The two methods differ only in the order of steps... 

From retrosynthetic Scheme 1 follows a synthesis of4-amino-3-carboxy-1,5-dihydro-2-pyrrolones (type Y R4 = OH or OR) that needs malonic acid or malonate as starting material. Such reaction is expected to give low yields due to the limited tendency of malonate to undergo enolization (see Table I) yet it is frequently the only solution at hand. 

Retrosynthetic Scheme 1 shows the general synthetic approach. Under certain conditions, the preparation of the /3-ketocarboxylic acids R4—CO—CH2—COOH or their esters might become the largest chal-... 

Synthesis. Outline a retrosynthetic scheme for each of the following target molecules using the indicated starting material. Show (1) the analysis (including FGI, synthons, and synthetic equivalents) and (2) the synthesis of each TM. 

Another relevant example is the total synthesis of the macrolide glacosporone, a germination self-inhibitor from the fungus Colletotrichum glocosporioides. The retrosynthetic scheme shows the important role played by the dithiane anion (Scheme 8). 

SCHEME 4. Retrosynthetic scheme for the synthesis of the GPI-anchor of T. cruzi trypomastigote glycoproteins, lacking Gal/ in the glycan, showing key building blocks and D-mannose monosaccharide intermediates. 

The Knowledge base-Oriented System for Synthesis Planning (KOSP) was developed by Satoh and Funatsu and uses reaction databases for the retrosynthe-sis approach [115]. KOSP provides strategic site-pattern perception and precursor skeleton generation and evaluates retrosynthetic schemes. This system is based on knowledge bases in which reactions are abstracted by structural or stereo characteristics of reaction sites and their environments. 

Rohitukine (7) has been synthesised by the group led by de Souza as part of their confirmation of the identity of the compound they isolated from Dysoxylum binectariferum [8]. An outline of the method used is shown in Fig. (4). It also followed a retrosynthetic scheme. 

A more detailed assessment of this retrosynthetic scheme, however, reveals a potential difficulty, if the relay model outlined above is valid. Assuming that the cataly.st attacks the 4-pentenoate entity of the envisaged cyclization precursor 34, a fairly stable six-membered chelate structure may be obtained which can intercept the catalyst in an unproductive form. 

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