Erythronolide rearrangement

Enantiomers, preferential crystallization of 59 Endo selectivity 798 Ene reactions 808, 809 Enones, synthesis of 732 Enthalpies of formation 102, 103 Enynes, synthesis of 956 Enzymatic kinetic resolution 829 Epimerization 399 Episulphides, oxidation of 237 Episulphones 650, 775 Episulphoxides, photolysis of 742 a,/J-Epoxysulphones reactions of 811, 812 rearrangement of 685 synthesis of 612 / ,y-Epoxysulphones 781 y,<5-Epoxysulphones 627, 628 Epoxysulphoxides reactions of 613 rearrangement of 744 synthesis of 327, 612 Erythronolides 831... 

Development of a novel route to the C-7 to C-13 portion e.g. 122) of erythronolides A and B (i.e. 121a and 121b) by Burke makes use of a stereoselective addition of an isopropenyllithium-derived cuprate to homochiral aldehyde (123) as a first, key step (Scheme 20). Formation of allylic alcohol (124) as the major product presumably reflects a 3 chelation controlled pathway vide supra) Subsequent handling of (124), which included as the second critical step a dioxanone to dihydropyran enolate Claisen rearrangement, produces three key subunits, including (122). 

As an application in natural product synthesis, the C -Cg macrolide subunit of ery-thronolide B aglycon is prepared by stereoselective cnolatc Claisen rearrangement of diox-anone 1 to dihydropyran 2533. Dihydropyran 2 is further transformed to give an intermediate in the synthesis of erythronolide B aglycon. 

So we concentrated on the synthesis of fragment 129. The two stereogenic centers at C-7 and C-8 were established from (7 )-2,3-isopropylidene glyceraldehyde 132 as shown in Scheme 22 via a sequence already employed in the total synthesis of erythronolide B (18). Stereotriad 135 is available in multigram quantities on this route via 133 and 134 (Scheme 22). After protection of the secondary OH as a p-methoxybenzyl (PMB) ether the base induced 1,3-rearrangement was achieved under standard conditions to furnish the desired olefin 137 (Scheme 23). 

In an amazing transformation, optically pure erythronolide template 927 is generated from 926 by a double dioxanone-dihydropyran [3,3] sigmatropic rearrangement [248] (Scheme 124). The template contains the fundamental 13-carbon framework of erythronolide A or B (600) with seven of its asymmetric centers established. The synthesis of 927 requires 18 steps to complete, and the genesis of all the stereochemistry can be traced to isobutyl D-lactate (913). It is speculated that the remaining six stereocenters of erythronolide B can be introduced by hydroboration of the three olefinic segments of the bis(dihydropyran) 926. 

The 2,4-di-C-methyl-D-galactopyranose derivative (16) has been rearranged to the furanose isomer (17) and hence to the derivative (18)(Scheme 4) required for the synthesis of an erythronolide ring fragment. 

Deslongchamps applied the equatorial selective Ireknd-Claisen rearrangement described previously (cf. Scheme 4.41) in a formal synthesis of erthyronoHde A (Scheme 4.119) [43]. The rearrangement of the Z-silyl ketene acetal proceeded via a chair transition state to establish the C4 and C5 stereocenters of erythronolide A. 

Epierythromycin A has been synthesized from a desosaminyl erythronolide precursor using the glycal rearrangement glycosylation procedure with a glycal obtained from cladinose. ... 

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