Subject Retrosynthetic analysis

Estrone (54, Chart 6) contains a full retron for the o-quinonemethide-Diels-Alder transform which can be directly applied to give 55. This situation, in which the Diels-Alder transform is used early in the retrosynthetic analysis, contrasts with the case of ibogamine (above), or, for example, gibberellic acid (section 6.4), and a Diels-Alder pathway is relatively easy to find and to evaluate. As indicated in Chart 6, retrosynthetic conversion of estrone to 55 produces an intermediate which is subject to further rapid simplification. This general synthetic approach has successfully been applied to estrone and various analogs. ... 

Our retrosynthetic analysis for lipid I is presented below [Scheme 2], Our protected version of lipid I employed acetate protective groups for the carbohydrate hydroxyls, methyl esters for each of the carboxyl groups in the pentapeptide side chain, and trifluoroacetate for the terminal amino group of the lysine residue. These base-cleavable protective groups could be removed in a single operation in the final step of our synthesis and would not subject the sensitive diphosphate linkage to acidic reagents or reaction conditions. 

A retrosynthetic analysis may well lead to a molecule recognizably derived from the chiral carbon pool. Presumably, the resulting synthesis will then be subject only to the vagaries encountered in the preparation of any target molecule, chiral or not. Unfortunately, the actual situation is not always that simple. If the target molecule contains more than one chiral center, the introduction of the later centers must be highly stereoselective to avoid diastereomer formation. As noted above, though, diastereomers usually are separated fairly readily and the loss of a small amount of... 

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. 

A proposal for the synthesis of the target molecule, irrespective of its complexity, can be elaborated by retrosynthetic analysis based on the disconnection approach. For chiral molecules this approach results in a proposal for the synthesis of racemic target molecules. Preparation of one enantiomer, or optically pure target molecule, enables asymmetric synthesis. 1-(Pyridine-3-yl)propan-l-ol is selected to demonstrate various retrosynthetic approaches to this relatively simple target molecule and to show the complexity of asymmetric syntheses of the preferred enantiomer. An introductory example is elaborated in some detail to familiarize the reader with the philosophy behind retrosynthetic analysis and to underline the need for chiral information in the reacting system to complete asymmetric synthesis. Today chiral variants of synthetic reactions are the subject of intensive research, and it is said that their number is limited only by the creativity of the organic chemist. 

Recently the total synthesis of natural (-)-sedacryptine (228) was accomplished in an organocatalyzed Mannich/ aza-Achmatowicz/A-acyliminium ion reaction sequence in 0.6% overall yield over 14 steps (Scheme 11.50) [155], Retrosynthetic analysis revealed piperidinone 223, which was accessible from sulfone 221 via asymmetric Mannich reaction, protection of the carbonyl group, and aza-Achmatowicz reaction, to be a promising intermediate toward (-)-sedacryptine (228). Then, addition of allyltri-methylsilane to the in situ formed A-acyliminium ion afforded the c -substituted piperidinone 224 as single diaste-reomer. Compound 225, which was subjected to ozonolysis. 

---