Synthesis polyhydroxylated natural products

Applications of Allylboronates in the Synthesis of Carbohydrates and Polyhydroxylated Natural Products... 

The stereoselective synthesis of carbohydrates from acyclic precursors is a research topic that has attracted considerable attention over the past decadeT Efforts in this area are easily justified and have maximum impact particularly when directed toward rare sugars or other polyhydroxylated molecules that are not conveniently accessed via classical "chiron" approaches.2 An underlying theme of such efforts, of course, is the development of practical synthetic methodology that will find broad application in the enantio- and diastereoselective synthesis of natural products, their analogues, and other compounds of biological interest. 

The reaction of carbonyl compounds and allylmetal reagents is an important transformation in organic synthesis. Advances in stereoselective carbonyl allylation reactions have been spurred by interest in the synthesis of polypropionate-derived natural products, carbohydrates and other polyhydroxylated compounds. These reactions are ideally suited for the construction of stereochemically rich acyclic skeletons. Additionally, cyclic polyether-containing natural products, among others, have inspired chemists to investigate ring-closing allylation reactions. This review will focus on recent developments in the allylation reaction, with special emphasis on its application towards the synthesis of natural products. 

Synthesis of (—)-Laulimalide. Different approaches to the (3-hydroxy sulfone moiety needed for the olefination reaction are frequently used in the synthesis of natural products. For instance, a very common strategy consists of carbonyl reduction of the corresponding a-ketosulfone followed by reductive elimination. This sequence is employed in the synthesis of polyhydroxylated indolizidine alkaloids (Eq. 121),207 (+)-dihydromevinolin,268 pleraplysillin-1,269 amphidino-lide B,270 and the novel antitumor agent (—)-laulimalide (Eq. 158).271... 

The Sharpless asymmetric epoxidation procedure has become invaluable in the synthesis of complex natural products although the precise organometallic nature of this reaction is not yet known. Of particular merit, the research groups of Sharpless and Masamune have elegantly illustrated the utility of the procedure by the synthesis of saccharides and polyhydroxylated natural products. 

The efficient addition-cyclization sequence described above could be successfully applied to the preparation of the polyhydroxylated y-amino acid (-)-detoxinine [73], The crucial key step in this fairly short synthesis is the chelate-controlled addition of lithiated benzyloxyallene 120 (R = Bn) to the chiral N-benzyl-substituted imine 121 as shown in Scheme 8.31. The required skeleton of the natural product was generated in good overall yield. 

This catalytic epoxidation method has been applied to the synthesis of a variety of natural products, particularly polyhydroxylated compounds, including carbohydrates (54) and macrolides. In addition, this reaction has been used for commercial synthesis of disparlure, a gypsy moth pheromone [J. T. Baker Co. (55) and the Shanghai Institute for Organic Chemistry (56)], and more importantly, glycidol, a versatile intermediate for synthesis of /3-blockers and other functionalized chiral molecules (Arco Co.) (Scheme 23) (57). 

Several a,j5-unsaturated (5-lactones are produced by higher plants, and it is speculated that they originate biogenetically from the respective 1,3-polyhydroxylated acids. The synthesis of (— )-tarchonanthuslactone (615) exemplifies the utility of asymmetric 1,3-polyols in natural product synthesis (Scheme 90) [145]. All- y -epoxide 606 is transformed into the natural product 615 in good overall yield using only standard synthetic operations. 

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