Synthetic studies in anthracyclinones and ancillary topics

Abstract

Section 4 illustrates another approach for the synthesis of a synthon for digitopurpone and also for the synthesis of adriamycinone (Scheme III). Scheme III 0 H?C?O?C- CO?C?H? OCH? OCH? CO?H In Section 5, a third approach in which 2,5-diethoxycarbonyl-cyclohexane-1,4-dione mono ketal was used as a Michael donor, is described (Scheme IV). Scheme IV 0 A CO?C?H? H?CO OCH? H?CO OCH? CO?C?H? CO?CH?

Chapter 2: Aromatisation of dihydrobenzene derivatives to corresponding benzenoid compounds is a facile reaction brought about by a variety of reagents. 2,5-Diethoxycarbonylcyclohexane-1,4-dione, which exists largely in dienolic form, is converted to diethyl 2,5-dihydroxyterephthalate by a number of reagents. However, less well-known is the conversion of cyclohexane-1,4-dione derivatives to monohydroxyphenolic derivatives. Previously, this has been reported using aqueous HCl and HBr (Gundu Rao and M.V. Bhatt). While attempting to prepare the mono ketal of 2,5-diethoxycarbonylcyclohexane-1,4-dione, we found that similar transformation can be carried out by silicon tetrachloride (Scheme V). Scheme V R = H, R' = CH?, C?H? R = COO?C?H?, R' = CH?, C?H? R = CH?, R' = C?H?, C?H? R = C?H?, R' = C?H? R = CH?, R' = CH?, C?H? R = C?H?, R' = CH?, C?H?, benzyl

Chapter 3: While attempting to selectively deethoxycarbonylate only one of the ester functions in a multifunctional compound, a general method was developed for the cleavage of esters. This method, consisting of refluxing an ester with aluminium chloride-sodium iodide system in acetonitrile, shows a high degree of selectivity among various ester groups. The ease of ester cleavage is in the order: benzyl > methyl > allyl > isopropyl >> aryl. In fact, the selectivity is so marked that it is greatly possible to cleave one of the ester functions without affecting the other, with proper choice of conditions and ester functions. A feature of this reagent is that it does not ordinarily cleave aryl esters.

Chapter 4: A new approach to deethoxycarbonylation of an ester function of highly substituted ?-keto ester was examined. Oximation of the keto function, providing a neighbouring group which can be converted into an effective and selective nucleophile under mild conditions, forms the basis of this method (Scheme VI). Scheme VI - L BOH