Actinobolin via the anomeric effect

Abstract

Actinobolin (la), isolated by Haskell and Bartz2 in 1959 from cultures of Streptomyces griseoviridies var. atrofacienes, found little favor as an antibiotic, one reason being the fact that it was not readily absorbed through the stomach walls. This demerit, coupled with the subsequent discovery that the antibiotic hardens enamel,3 has caused a reawakening of interest in actinobolin as a cariostatic agent. The discovery, 20 years later, of the antitumor agent bactoboiin,4 structurally related although not a congenor, has enhanced interest in these isocoumarins.5 An elegant synthesis of (+)-l, based on an intramolecular Diels-AIder strategy, was recently reported by 7In this paper, we report an alternative route to A'-acetyldesalanylactinobolin [(+)-lb] (Scheme I).The structural elucidation of la was a tour de force for Munk and Haskell.7,8 X-ray9 and NMR7 8 data indicated that the molecule exists in conformation Id, a fact that manifests itself in the ease with which the C-9 and C-10 hydroxyls can be acetonated.8•10 For purposes of synthetic strategy, this glycol residue would have been easier to deal with if it were trans diaxial, as in the unpopulated conformer le, since an epoxide, for example, la, would then be a logical synthon. Our recent studies on annulated pyranosides12 have shown that systems such as la conform to the dictates of the anomeric effect,13 even in the face of multiple(1) This work is supported by NTH (AI 20117) and the donors of the Petroleum Research Fund, administered by the American Chemical Society.

Magnesium‐Catalyzed Proficient Reduction of Oximes to Amines Using Ammonium Formate

“…Although the addition to the C5 5N bond of imines, hydrazones and oximes are well known, [3] the development of such reaction is often limited by the poor electrophilicity of the C5 5N carbon atom. Numerous new reagents have been developed for the reduction of oximes to amines including NaBH4, [3,4] LiAlH 4 [5,6] and indium/acetic acid. [7] Though some of these are widely used, still they have limitations based on chemo-selectivity and economic considerations.…”

Unsaturated Sugars: A Rich Platform for Methodological and Synthetic Studies

“…These compounds proved to be versatile substrates in dipolar, photochemical and Diels-Alder cycloadditions. Thus, 1,3-dipolar cycloaddition of diazomethane to enone 74f took place at room temperature in ethyl ether and led to pyrano-pyrazoline 101 in [83] also underwent smooth addition to enone 106 to generate adduct 108 in high yield (Scheme 25d) [84]. Both DielsAlder additions took place exclusively from the -face.…”

“…The fact that the ethoxy group in 109a is axial suggested that the anomeric effect, that had already controlled the stereochemistry of the cycloaddition, was also responsible for this preferred conformation. The actinobolin synthesis by Rahman and Fraser-Reid took full advantage of these issues [84].…”

“…However, based on the above mentioned issues, the authors expected that trans-diaxial opening of a supposedly preferred "anomeric effect" conformer 110a, would lead to actinobolin rather than to a diastereoisomer arising from oxirane ring opening of the "nonanomeric effect" conformer 110b. According to these guidelines, the synthesis of actinobolin started from cycloadduct 108 [84] (Scheme 28), readily prepared by reaction of methyl 2,3,6-trideoxy--D-hex-2-enopyranosid-4-ulose (106) with Danishefsky's diene (107). Thus, oximation of 108, followed by lithium aluminum hydride reduction afforded allylic alcohol 112, which upon oxidation (MnO 2 ), followed by -acetoxylation with lead tetraacetate led to acetoxy ketone 113, as the sole isomer.…”

4Å molecular sieves catalyzed ring-opening of epoxides to 1,2-diacetates with acetic anhydride

“…2 Therefore, direct transformation of epoxides to the 1,2-diacetates is a very attractive reaction. A review of the literature shows that this transformation has been achieved with the reaction of epoxides and acetic anhydride in the presence of catalysts or reagents such as HCl, ZnCl2, 3 (NH4)3(PMo12O40)6, 4 (TBA)4PFeW11O39·3H2O, 5 Cp2TiCl2, 6 (n-Bu)4NOAc, 7 11-13 and 15), and the others were limited in scope. Some of the previously-reported studies required expensive, exotic or hazardous reagents, extended reaction times, and/or limitation to a narrow range of epoxides.…”