'Naked sugars of the second generation': Asymmetric synthesis of long-chain polypropionates and analogues starting with acetone

Abstract

Homochiral Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1'R)-or (1's)-camphanate are transformed readily into polypropionate fragments containing four or five contiguous stereogenic centres. They can be condensed via cross-aldolizations to lithium enolates of 7-oxabicyclo[2.2.l]heptan-2-ones with high diastereoselectivity generating long--chain systems containing up to eleven stereogenic centres and tertiary alcoholic moieties.A large variety of natural products of biological interest contain polypropionate fragments (chain with alternating hydroxy and methyl substituents).l Among the many macrolide antibiotics, erythronolides (aglycons of erythromycins) have become the yardstick for measuring progress in the efficiency of stereoselective syntheses.3~4 The shortest synthesis of (9S)dihydroerythronolide A (1) is the linear approach of Stiirmer et aZ.3a Other more convergent approache@ imply a retrosynthetic disconnection at the C(6)--C(7) bond as illustrated with the synthesis of Stork et aZ.4 which couples the fragments 3 and 4 to generate 2 with high diastereoselectivity. If intermediate 3 could be derived from 5 which is the 2,3diepher of 4, one can envision these two polypropionate fragments and analogues to derive from the uronolactones 7 and 6, respectively, that w i l l be generated from the same homochiral(1R,4R)-1,5dimethyl-7-oxabicyclo[2.2.1]-hept-5-en-2-one ((+)-ti). This chiron and its enantiomer (-)-8 are obtained readily.2 5 u 3 4 u 7

Expeditious Asymmetric Synthesis of Polypropionates Relying on Sulfur Dioxide-Induced C–C Bond Forming Reactions

“…The alkaline hydrolysis of the latter liberates the chiral auxiliary (a carboxylic acid) which can be recycled. The bicyclic compounds so obtained permitted Vogel and co-workers to prepare several stereotetrads [51,52]. Alternatively, Plumet and Arjona used a Diels-Alder reaction between furan and acrylic acid which provided, after several transformations, a complete library of all possible stereotetrads [53,54].…”

Concise Synthesis of Complicated Polypropionates through One‐Pot Dissymmetrical Two‐Directional Chain Elongation

“…They are found in diverse classes of natural products with biological and medicinal interest, [1] and many applied synthetic approaches to polypropionates have been reviewed recently. [2,3] All the synthetic methods are multistep processes involving functional group construction, selective protection steps, and installation of the stereogenic centers. For practical as well as environmental and economic reasons, the number of chemical operations should clearly be reduced to a minimum.…”

Total Asymmetric Synthesis of a New 9,12-Anhydroerythronolide Aglycone

“…In a preliminary communication [8], we showed that the partially protected secoacid of the 9,12-anhydroerythronolide aglycon 6 can be derived from the Diels-Alder adduct (À)-7 of 2,4-dimethylfuran to 1-cyanovinyl (1'S)-camphanate (a −naked sugar of the second generation× [9]) and (3R,4S,5R,6S)-7-benzyloxy-3,5-(isopropylidenedioxy)-4,6-dimethylheptane-2-one (()-8) [10]. We present now the details of these transformations and the conversion of the seco-acid to the corresponding macrolide 9.…”