A Concise Synthesis of the Naphthalene Portion of Purpuromycin

Abstract

A concise synthesis of naphthalene compounds for incorporation into a synthetic sequence for the rubromycin family of natural products is presented. These highly substituted naphthalenes are generated in seven and nine steps, respectively, from 2,4,5-trimethoxybenzaldehyde. Three ring-forming methods were explored and the controlled oxygenation of different positions was investigated to yield differentially substituted/protected systems. Key steps to the final products include a Stobbe condensation to form the ring system and a novel series of regioselective oxidations to introduce the required oxygen functionality. These naphthalene products incorporate orthogonal protecting groups and are suitable for combination with a variety of coupling partners.

A Convergent Total Synthesis of the Telomerase Inhibitor (±)‐γ‐Rubromycin

“…Our synthesis started with the preparation of pentamethoxynaphthyl-substituted alcohol 10 which was accessible from 2,4,5-trimethoxybenzaldehyde over 10 steps on a multigram scale following a procedure described by Kozlowski. [21] Unfortunately, we were not able to convert alcohol 10 into a compound with a suitable leaving group such as bromide 8; due to the extraordinarily electron-rich naphthalene ring the electrophile to be generated is apparently too labile (Scheme 2). As a consequence, the planned strategy could not be applied to the synthesis of enone 6, although this approach was successful for simpler benzyl-substituted model substrates (e.g.…”

Eine konvergente Totalsynthese des Telomerase‐Inhibitors (±)‐γ‐Rubromycin

“…Derartige Verbindungen sind nicht nur attraktiv, da sie bereits alle zum Aufbau des Isocumarinfragments bençtigten funktionellen Gruppen enthalten, sondern auch wegen ihres Oxidationsgrades als Naphthochinon. Unsere Synthese begann mit dem Aufbau des Pentamethoxynaphthyl-substituierten Alkohols 10, der nach einer von uns modifizierten Methode von Kozlowski [21] ausgehend von 2,4,5-Trimethoxybenzaldehyd in 10 Stufen im Multigramm-Maßstab zugänglich war. Das Enon 6 sollte aus der Umsetzung des Bromids 8 mit lithiiertem Methoxyallen (9) [20] hervorgehen (Schema 1).…”

“…Unsere Synthese begann mit dem Aufbau des Pentamethoxynaphthyl-substituierten Alkohols 10, der nach einer von uns modifizierten Methode von Kozlowski [21] ausgehend von 2,4,5-Trimethoxybenzaldehyd in 10 Stufen im Multigramm-Maßstab zugänglich war. Es gelang allerdings nicht, den Alkohol 10 in eine Verbindung mit einer geeigneten Abgangsgruppe, z.…”

Practical synthesis of polysubstituted naphthalene derivatives via HNTf2-catalyzed benzannulation reaction

“…[1][2][3][4][5][6][7][8][9] Additionally, this particular aromatic structure can be found in numerous optical and electronic materials [10][11][12] and constitutes the backbone of many chiral ligands. 13 Nafacillin, 14 suramin, 15,16 which play a vital role in the control of microbial infection, are typical examples of drugs that present a naphthalene moiety ( Figure 1).…”