Showing papers by "Tomas Hudlicky published in 2016"

Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives.

Abstract: This update covers the syntheses of Amaryllidaceae alkaloids since the publication of the last major review in 2008. A short summary of past syntheses and their step count is provided for the major constituents; pancratistatin, 7-deoxypancratistatin, narciclasine, lycoricidine, lycorine, and for other natural constituents, as well as for unnatural derivatives. Discussion of biological activities is provided for unnatural derivatives. Future prospects and further developments in this area are covered at the end of the review. The literature is covered to the end of August 2015.

Chemoenzymatic Total Synthesis of (+)-Galanthamine and (+)-Narwedine from Phenethyl Acetate.

Abstract: The stereoselective total synthesis of unnatural (+)-galanthamine starting from phenethyl acetate is described. Chirality was introduced via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis-cyclohexadi-enediol, configuration of which provided the absolute stereochemistry of the ring C of (+)-galanthamine. Intramolecular Heck cyclization was used to form the quaternary carbon and dibenzofuran functionality. The synthesis of (+)-galanthamine was completed in a total of ten steps and an overall yield of 5.5 %. Experimental and spectral data are provided for all new compounds.

Chemoenzymatic Total Synthesis of Hydromorphone by an Oxidative Dearomatization/Intramolecular [4 + 2] Cycloaddition Sequence: A Second-Generation Approach

Abstract: A second-generation approach to the synthesis of hydromorphone by oxidative dearomatization/Diels–Alder cycloaddition was investigated. Detailed analysis of the stereochemical outcome of the [4 + 2] cycloaddition was performed first on a truncated model system as well as on the material leading to ent-hydromorphone. The stereochemical assignments were made by NMR and X-ray methods. The second-generation synthesis of hydromorphone was completed in both enantiomeric series. Improvements in the dearomatization conditions were attained using hypervalent iodine reagents instead of Pb(OAc)4. Electrochemical methods of oxidative dearomatization were also investigated. New conditions enabling the rearomatization of ring A from the methoxyketal were developed, and a formal synthesis of the natural enantiomer of hydromorphone was completed. Experimental and spectral data are provided for all new compounds.

Chemoenzymatic Synthesis of Pleiogenone A: An Antiproliferative Trihydroxyalkylcyclohexenone Isolated from Pleiogynium timorense.

Abstract: The first total synthesis of polyhydroxylated cyclohexenone 1, isolated from Pleiogynium timorense and named pleiogenone A, is reported that also serves as a proof of structure and absolute configuration. Enzymatic dihydroxylation of benzoic acid with R. eutrophus B9 provided enantiomerically pure diene diol 6. Elaboration of the carboxylate moiety to the alkyl side chain was followed by singlet oxygen cycloaddition to furnish an endoperoxide whose reduction with thiourea led to cyclitol 19. Several protective operations were required before oxidation and the final extension of the side chain by a Wittig reaction. After final deprotection of the acetonide functionality the desired pleiogenone A (1) was obtained in 14 operations from benzoic acid.

Synthese von Inhaltsstoffen der Amaryllisgewächse und nichtnatürlichen Derivaten

Abstract: Dieser Aufsatz behandelt die Fortschritte bei der Synthese von Amaryllidaceae-Alkaloiden seit der Veroffentlichung des letzten umfassenden Ubersichtsartikels im Jahr 2008. Synthesen der Hauptinhaltsstoffe – Pancratistatin, 7-Desoxypancratistatin, Narciclasin, Lycoricidin und Lycorin – sowie anderer naturlicher Inhaltsstoffe und nichtnaturlicher Derivate werden vorgestellt, und die biologische Aktivitat der nichtnaturlichen Derivate wird diskutiert. Ein Ausblick und weitere Entwicklungen auf dem Gebiet beschliesen den Aufsatz. Die Literatur wurde bis Ende August 2015 berucksichtigt.

Contributions of Ernest Wenkert to the Use of Cyclopropanes in Synthesis – Impact, Reflections, and Recollections

Abstract: This essay describes Ernest Wenkert’s contributions to the chemistry of cyclopropanes and their use in synthesis. The impact of his work on the careers of others, especially including the development of cyclopropane-based research in the Hudlicky group, is addressed, along with reflections on his mentorship. Personal recollections from some of his past students are provided at the end of the article.

Chemoenzymatic Synthesis of Pleiogenone A: An Antiproliferative Trihydroxyalkylcyclohexenone Isolated from Pleiogynium timorense.

Abstract: The first total synthesis of polyhydroxylated cyclohexenone 1, isolated from Pleiogynium timorense and named pleiogenone A, is reported that also serves as a proof of structure and absolute configuration. Enzymatic dihydroxylation of benzoic acid with R. eutrophus B9 provided enantiomerically pure diene diol 6. Elaboration of the carboxylate moiety to the alkyl side chain was followed by singlet oxygen cycloaddition to furnish an endoperoxide whose reduction with thiourea led to cyclitol 19. Several protective operations were required before oxidation and the final extension of the side chain by a Wittig reaction. After final deprotection of the acetonide functionality the desired pleiogenone A (1) was obtained in 14 operations from benzoic acid.

Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives

Abstract: Review: [recent total syntheses of the title natural products and structure—activity relationships; 187 refs.