Robert W. Irvine

Anthracyclines XVII: The synthesis of 2 - fluoro and 3 - fluoro -4-demethoxydaunomycin

Abstract 2- Fluoro and 3 - fluoro-4-demethoxydaunomycinone have been prepared by phthalide annelation of the quinone monoacetal(10), which was in turn prepared from the previously described fully oxygenated Ketone (1). Extensions of this approach to permit inclusion of a chiral induction step are also evaluated. The title compounds were prepared by glycosidation of the appropriate racemic aglycones and the merits of different methods of attaching the sugar are discussed.

A caveat regarding chiroptical measurements of chiral anthracyclinones

Abstract The specific rotations of anthracyclinones are shown to exhibit dramatic variation induced by protic solvents. The significance of this finding to the evaluation of optical purity of synthetic anthracyclinones is discussed.

A high-yielding enantiospecific synthesis of (−)-7-deoxydaunomycinone

Abstract A comparison is made between two regiospecific modes of base-catalysed condensation of 4 (or 7)-methoxy-3-phenylsulfonyl phthalides with chiral bicyclic quinone monoketals, one of which occurs in 95% yield and forms the basis of the first enantiospecific total synthesis of (−)-7-deoxydaunomycinone (3).

Allylic vs homoallylic control of stereospecificity in the epoxidation of 3(1'-hydroxyethyl)-5,8-dimethoxy-1,2-dihydronaphthalen-1-ol: implications for the synthesis of chiral anthracyclines

Abstract The stereochemistry of the epcxidation of the title compound with t-BuOOH catalysed by VO(acac) 2 is subject to exclusive homoallylic control. Secondary allylic alcohols in the side chain regain their normal controlling influence over diastereoselection only when the homoallylic group is blocked.

A new route to 3-hydroxyphthalides : Application to the synthesis of racemic [5-13C] daunomycinone.

Abstract Lithiation (n-BuLi) of the (3′-methoxyphenyl) oxazoline ( 2a ) occurs specifically at C2′ and, following carboxylation (CO 2 / 13 CO 2 ) and esterification, yields the phthalate derivative (e.g. 5a ). Elaboration of the oxazoline-ring furnishes the related aldehydes which spontaneously cyclise to form the 3-hydroxyphthalides ( 8 / 10 ). The title[5- 13 C] anthracyclinone ( 20 ) is produced from 3-cyanophthalide ( 11 ) in good yield and with excellent isotopic efficiency.