Pseudomonic acids rearrangements

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

The rearrangement provides a stereocontrolled synthesis of the C-pyranoside 2, present in pseudomonic acids.2... 

D. P. Curran, An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mon-Claisen rearrangement, Tetrahedron Lett. 23 4309 (1982). 

D. P. Curran and Y. Suh, Synthetic applications of a substituent controlled Claisen rearrangement. Preparation of advanced intermediates for the synthesis of pseudomonic acid, Tetrahedron Lett. 25 4179 (1984). 

Application of Claisen methodology led to a number of successful total syntheses of natural compounds. Thromboxane B2 has been synthesized from a 4,5-unsaturated sugar derived from D-glucose [126]. The Ireland-Claisen rearrangement [127] is also the key reaction used to control the introduction of the right wing of pseudomonic acids [128]. 

H. H. Baer and Z. S, Hanna, The preparation of amino sugars and branched-chain sugars by palladium-catalysed allylic substitution of alkyl hex-2-enopyranosides. Can. J. Chem. 59 889 (1981). D. P. Cuiran, An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mon-Claisen rearrangement. Tetrahedron Lett. 23 4309 (1982). 

Ring opening of 27 by treatment with anilide ion followed by a second Eschenmoser rearrangement leads to 28, a key intermediate in the synthesis of naturally occurring pseudomonic acids, a group of compounds with antimicrobial and antimycoplasmal activity416. 

A substituent-controlled "mono-Clatsen" rearrangement was also employed as a key reaction in the construction of chiral intermediates for the synthesis of pseudomonic acids from diacetyl-L-arabinal418. The acetate groups of the starting material are chemically differentiated by virtue of the accelerated rate of the first Claisen rearrangement (ascribed to a vinylogous anomeric effect). 

In the total synthesis of pseudomonic acid C, Barrish et al. used the rearrangement of ester 45 as a key step [26]. With the (Z)-configured ester 45 the anti-product was obtained nearly exclusively (> 95% ds), while the corresponding ( )-ester showed a much lower diastereoselectivity. 

Kinetic measurements of the reaction rates ki and k2 for the individual rearrangement steps revealed that the first Claisen rearrangement proceeded 20 times faster than the second one. This unexpected chemoselectivity proved useful for the preparation of key intermediate 59 in the synthesis of pseudomonic acid C 60 (Scheme 11). 

In another approach to pseudomonic acid, Fleet and Gough have outlined an enantiospecific synthesis of (153) from D-arabinose, which, after ring-opening to (154) with anilide ion followed by Claisen amide acetal rearrangement, was... 

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