Lactic chiral building block

In the last two decades, chiral receptors containing amidic functions were designed almost exclusively for binding protected amino acids [49-57], oligopeptides [54,58], and lactic [59], tartaric [60,61] or camphoric acid derivatives [62]. Usually, chiral building blocks such as spirobifluorene [49, 60], binaphthalene [51,57],or amino acid chains containing macrocycles [52-56,58] were employed. An interesting receptor was synthesized via connection of the calix[4]arene moiety with an aza-crown derivative [61]. 

The synthesis of PS-5 was achieved by treatment of silylimine of 0-protected (S) lactic aldehyde with the lithium enolate of /-butyl butanoate. The reaction is highly diastereoselective affording almost completely the trans a2etidinone with the natural configuration at C3. This azetidinone was converted, by sequential Jones and Baeyer-Villiger oxidation of hydroxyethyl side chain to the 4-acetoxy doivative that represents a most useful chiral building block fcv the synthesis of final carbapenem PS-5 via the Merck procedure (Scheme 8). 

Chiral information was introduced through the C3-building block 5 derived from lactic acid. The remaining two siereogenic centers in the natural product were provided under substrate control in the course of a domino cyclization... 

The third major source of chiral pharmaceuticals involves synthesis using naturally occurring chiral molecules as starting materials (5,17). Those compounds most generally used are carbohydrates, amiiu) acids, terpenes, and smaller, microbiologically derived compounds such as lactic acid or tartaric add. In addition, the synthetic chemist now has in his or her repertoire a variety of rather standard building blocks derived by manipulation of the natural substances a list of such compounds has been compiled (5). 

Recently, Steckhan and coworkers [485,486] have reported that anodic methoxyla-tion of chiral 5-methyl- and 5-chloromethyl-2-oxazolidinones followed by Lewis acid-catalyzed allylation provides 4-allyl products highly diastereoselectively. Similarly, anodic methoxylation of cyclic dipeptides and dipeptolides derived from chiral a-amino acid [487] or a-hydroxy acid [488] provides useful chiral synthetic building blocks, as in Eq. (64). a-Alkoxylation of lactic amide derivatives was also reported [489]. However, the diasteros-electivity was low. 

Acetylenic diols, potential building blocks for the synthesis of L-hexoses and L-pentoses, are available with either syn or anti configuration using TBPS-protected L-lactic acid derivatives as the chiral source (Scheme 108). 

Before we can declare the photolactonization-based synthesis of lichen macrolide 100 a success, we need a reference case. One synthetic reference leading to 100, in which the complete set of stereogenic centers was introduced with no stereoselection, i.e., using chiral, nonracemic building blocks from the chiral C pool [107] (in this case D-mannose and D-lactic acid), was designed and carried out in Frankfurt, too Scheme 47). 

Optically active lactones are valuable building blocks in organic synthesis (4) and in the preparation of optically active biodegradable polymers (7,5). Several chemical methods for producing these compounds and their corresponding polymers have been explored (6) but unfortunately all of these methods are either experimentally cumbersome or afford the lactones with only modest enantioselectivities. Examples of chemically prepared optically active polyesters include poly(a-phenyl-P-propiolactone) (7), poly(a-ethy(-a-phenyl-P -propiolactone) (S, 9), poly(a-methyl-a-ethyl-P-propiolactone) (70) and poly(lactic acid) (77, 72). Use of enantioselective polymerization catalysts to carry out stereoelective polymerizations of racemic lactones has produced mixed results. For example, stereoelective polymerization of [/ ,S]- P-methyl-P-propiolactone with a catalyst from Zn ( 2115)2 and [7 ]-(-)-3,3-dimethyl-l,2-butanediol showed only a small enantiomeric enrichment in the final polymer (75). Stereoselective copolymerizations of racemic (LL/DD monomers) and meso (LD monomer) lactides using chiral catalyst that gives heterotactic and syndiotactic PLA, respectively have also been studied (77). 

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