Olivomycin synthesis

A similar synthetic strategy was applied in the synthesis of menogaril 83, another important anthracycline antitumour antibiotic, and to the synthesis of the tricyclic core of olivin 87, the aglycon of the antitumour antibiotic olivomycin [61,62]. In both cases a tandem benzannulation/Friedel-Crafts cyclisation sequence yielded the tetracyclic and tricyclic carbon core, respectively (Scheme 42). 

Our development of the tartrate ester modified allylboronates c.h suggested to us that many of these problems could be avoided by using the reaction of a chiral aldehyde and a chiral allylboronate as a means of establishing the stereochemistry of the sugar backbone. This strategy has been used in our synthesis of the AB disaccharide unit of olivomycin A (Figures 16, 17).3 ... 

The synthesis of disaccharide 61 is reasonably efficient (10 steps from 53,17% overall yield) and is readily amenable to scale up. Nevertheless, in contemplating extensions of this chemistry to the synthesis of differentially protected derivatives of D-olivose (e.g., 63, Figure 18) needed for construction of the olivomycin CDE trisaccharide, it became apparent that this approach is unattractive because the required starting... 

Figure 15. Reactions of epoxyalcohol intermediates in synthesis of olivomycin monosaccharides.

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

The method was used for oxidation of an unsaturated nitrile (1) to an aromatic acyloin (2) in a projected synthesis of a model for olivin (4), an aglycone of olivomycin antibiotics.2... 

For the synthesis of Olivomycin A. the Roush group used a crotyl ether to protect a phenolic hydroxyl group,42 In the final lap of the synthesis, deprotection of the phenolic crotyl ether in 226.1 was achieved with Pd(0) and tributylstan-nane [Scheme 4.226]. No harm befell the sensitive cyclopentylidene acetal and chloroacetate groups. 

Raney nickel is occasionally used as a catalyst for the cleavage of BOM ethers and it will remove a BOM ether without detriment to a / -methoxybenzyl ether, Roush and co-workers used Raney nickel in its traditional role as a desuifurisa-tion agent and as a hydrogenation catalyst in order to remove two phenylthio ethers, one phenylseleno ether and a BOM group in the penultimate step of a synthesis of Olivomycin A [Scheme 4.276].428... 

On the other hand, Roush and coworkers reported the synthesis of the functionalized C-D-E trisaccharide precursor of Olivomycin A, in which, particularly, the 2-deoxy-2-iodo-3-methyl-Q -L-mannop)Tanosyl linkage was stereoselectively introduced by using the glycosyl acetate donor (O Scheme 26) [34], This new a-glycosylation protocol was applied to the synthesis... 

In their synthesis of olivin, the aglycon segment of olivomycin A, Roush and coworkers used a highly diastereoselective substrate-directed y-alkoxy allylation reaction to set the C(l ) stereocenter [80]. Thus, reaction of the aldehyde 90, derived from L-threonine, with the [(Z)-y-methoxyallyl]boronate 91 resulted in the highly diastereoselective formation of adduct 92. The stereochemistry of 92 is consistent... 

The electrophilic addition of arylbis(arylthio)sulfonium salts to glycals in the presence of alcohols, directly provide 2-thio-(5-glycosides with good stereoselectivity [162]. Stereoselective syntheses of [5-glycosides were also obtained from the reaction of 1,2-trans acetoxysele-nides, prepared by treatment of glycals with phenylselenyl chloride and silver acetate, in the presence of trimethylsilyl triflate [163]. Combined application of this method and the trichlo-roacetimidate method (see section 3.3) was suggested for the synthesis of functionalized precursors of the olivomycin C-D-E trisaccharide [164] (Scheme 34). 

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