Synthetic Approach toward Azinomycins

The len-half segment 14 of antitumor antibiotics azinomycins A and B was synthesized in optically pure form staning from D-fructose.The dipeptide 18, equivalent to the azinomycin A top-hall, was also synthesized via oxazolidinone intermediates.Azinomycins A and B are antitumor antibiotics isolated from the culture broth of strain Streptomyces griseofuscus S42227 by Nagaoka et al. in 1986.' Azinomycins were repofled to exhibit antitumor activities against P388 leukemia, P815 mastocyioma, B-16 melanoma, and Ehrlich carcinoma.'The structures of them, lacking absolute stereochemistry, were elucidated as 1 and 2 by spectroscopic method.3Recently, we proposed absolute configurations of C-18 and C-19 as 18% 19s by the total synthesis of the minor component 3 isolated from the same strain starting from D-glucose.4Although the amide 3 possesses all structural untts for the len-half moiety of azinomycins, it is not necessarily useful for the total synthesis of them.Therefore, from a synthetic point of view, the efficient synthetic method of the other ten-half equivalent is required.We describe here an easy access to the N-hydroxysuccinimide ester 4 using D-fructose as a chiral staning material and preparation of some model compounds for the total synthesis of azinomycins.The y-lactone 5 was available on a large scale from D-fructose by the procedure repotled.5Reduction of 5 with lithium aluminum hydride in etherltetrahydrofuran(1:l) afforded the triol 6% good yield.The triol 6 was treated with acetone in the presence of a catalytic amount of p-toluenesulfonic acid to give the diacetonide 7 .which was convened into the corresponding tosylate 8 by the usual method in 61% overall yield from 6.The diacetonide 8 was selectively hydrolyzed with 70% aqueous acetic acid at 55% to give the diol 9, which was oxidatively cleaved with sodium periodate and the resultant aldehyde was then oxidized by Jones reagent to give the carboxylic acid 10 in 67% overall yield from 8. The carboxylic acid 10 was protected as a benzyl