Total Synthesis ofrac‐γ‐Indomycinone by Baker–Venkataraman Rearrangement

Abstract

Keywords:Total synthesis / Anthrapyranone antibiotics / γ-Indomycinone / Baker-Venkataraman rearrangement / Radical brominationThe total synthesis of racemic γ-indomycinone (rac-3) was achieved by Baker-Venkataraman rearrangement of ester 11 to the diketone 12, acid-catalyzed cyclization to the anthrapyranone 13, followed by methyl ether cleavage and acetylation to 16, selective bromination of the branched side chain with simultaneous S N 1-type hydroxy substitution to 23 and

Novel 1,4,5,8‐Phenanthrenediquinones and Unusual Deoxygenation with Trimethylsilyl Iodide

“…However, with both reagents a clean halogenation at C-3 of the quinoid ring to form 5a or 5b was observed (Scheme 1). A similar bromination of an aromatic ring was previously noted in a reaction with boron tribromide, [11] but the chlorination with boron trichloride was unexpected. (4) with BCl 3 and BBr 3 , leading to the halides 5a and 5b, respectively.…”

General Approach to Anthrapyran Antibiotics Exemplified by the Synthesis of rac‐γ‐Indomycinone

“…From the polar fraction obtained by silica gel chromatography the γ-indomycinone methyl ether 24a was isolated, identical in all aspects with a previously prepared sample. [10] The methyl ether was subjected to ether cleavage by using boron trichloride to afford racemic γ-indomycinone (24b), identical with an authentic sample of the natural product kindly provided by Prof. Laatsch. [10] …”

“…[2][3][4][5][6][7][8][9][10] Side chains with different lengths are attached to C-2 of the anthrapyran core. Unfortunately, to date a common approach to the different aglycon cores with one, two, four, or six carbon atoms in the side chain at C-2 is missing.…”

“…In the following stages the synthetic route deviated from earlier procedures. [10] The aim was to incorporate the methyl branching of the side chain, present in most naturally occurring anthrapyran antibiotics, [1] at an early stage of the synthesis maintaining the flexibility in the nature of the final side chain. For that purpose, the propionyl ester 9 was prepared (98 %) from 8b and subjected to a lithium hydride catalyzed Baker-Venkataraman rearrangement [6,13,14] to afford the ethyl diketone 10 in 92 % yield.…”

“…This established an ethyl side chain in the subsequent acidcatalyzed cyclization to the anthrapyran 11. Since boron tribromide cleavage of aryl methyl ethers is prone to bromination of the aromatic nucleus, [10] the methyl ether in 11 was cleaved to the phenol 12a by employing boron trichloride (93 %).…”