A Formal Total Synthesis of Virantmycin: A Modular Approach towards Tetrahydroquinoline Natural Products

Abstract

A synthesis of an advanced intermediate towards the racemic form of the antiviral agent virantmycin has been developed featuring an intramolecular aza‐xylylene Diels–Alder reaction. The required arylthiocarbamate has been constructed using an efficient oxidative cyclization strategy. A novel synthetic approach to chlorine‐substituted allylic alcohols using an unprecedented palladium‐catalyzed cross‐coupling reaction of α,β‐unsaturated ketones and protected propargylic alcohols is reported.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Cycloaddition reactions for antiviral compounds

“…52 Several total syntheses 53 of racemic (6)-Virantmycin, natural (2)-Virantmycin, and the unnatural (1)-antipode were proposed, stressing the importance and the promising pharmacological profile of the substance. 54 The identification of biologically active organic compounds is of utmost importance both for basic research and drug development. However, one of the most versatile and convergent strategies for the construction of tetrahydroquinoline alkaloids is the HDA reaction of o-azaxylylenes, which are formed by a 1,4-elimination from a suitable benzylic halide precursor and suitable dienophiles.…”

Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers

“…virantmycin [4] and chartellin [5] ), have led to an increased awareness of these scaffolds. [8] Fort he in situ generation of aza-ortho-quinone methides various methods have been proven of value,among them the base-induced 1,4-elimination of ortho-chloromethyl aniline derivatives, [2][3][4]9] thermally induced dehydration of benzyl alcohols, [10] and photochemically induced enolizations of ortho-carbonyl anilides. [8] Fort he in situ generation of aza-ortho-quinone methides various methods have been proven of value,among them the base-induced 1,4-elimination of ortho-chloromethyl aniline derivatives, [2][3][4]9] thermally induced dehydration of benzyl alcohols, [10] and photochemically induced enolizations of ortho-carbonyl anilides.…”

Asymmetrische Brønsted‐Säure‐katalysierte Substitution von Diarylmethanolen mit Thiolen und Alkoholen zur Synthese von chiralen Thioethern und Ethern

“…B. Virantmycin [4] und Chartellin [5] ), die die Attraktivität dieser vielfältigen Intermediate steigern.…”

“…[1] Es ist vor allem der elegante Zugang zu Te trahydrochinolinen und Indolen [2,3] sowie die zunehmende Verwendung in komplexen Naturstoffsynthesen (z. B. Virantmycin [4] und Chartellin [5] ), die die Attraktivität dieser vielfältigen Intermediate steigern. [6] Dennoch sind Aza-ortho-chinonmethide,g erade im Vergleich zu den sauerstoffanalogen Chinonmethiden, [7] noch immer nicht ausreichend untersucht.…”