Use of 5-methoxy, 6-methoxy and 7-methoxy-α-tetralones in the Synthesis of Diterpenes, Sesquiterpenes and Other Natural Products

Abstract

The transformations of 5-methoxy, 6-methoxy and 7-methoxy-a-tetralones are described. Studies on the synthesis of diterpenes veadeiroic acid 12, triptolide 18, sesquiterpenes biflorin 25, mansonone F 26, cacalol 39 and a potential intermediate for 11-deoxydaunomycinone 59 from 5-methoxy-a-tetralone 1 are discussed. Several intermediates for diterpenoid compounds and a total synthesis of phytoalexin orchinol 53 from 6-methoxy-a-tetralone 2 have been accomplished. 7-Methoxy-a-tetralone 3 has proved to be a suitable starting material for a simple and short synthesis of cadinene dihydrochloride 45.

Diterpenoids

“…The use of methoxy a-tetralones in the synthesis of tricyclic diterpenes has been reviewed. 114 Four new podocarpanes and three 3,4-secopodocarpanes, exemplified by 27, have been isolated from Aleurites moluccana. 115,116 They were assigned the ent-configuration, which is unusual for podocarpanes.…”

Rapid Generation of 2‐Acyl‐4‐phenyltetralones from 1,1‐Diacylphenylcyclopropanes

“…The α‐tetralone scaffold can be found within numerous medicinally relevant compounds, such as cladosporone A ( 1 ), [1] actinoranone ( 2 ), [2] and aureomycin ( 3 ), [3] among others (Figure 1). Perhaps more critical is the role of α‐tetralones in synthesis, where they have been extensively exploited as versatile starting materials and intermediates in the generation of more complex molecules [4–9] . For instance, the industrial synthesis of the commonly prescribed selective serotonin reuptake inhibitor (SSRI) sertraline ( 4 ) proceeds via a critical α‐tetralone intermediate, dubbed sertraline tetralone ( 5 , Scheme 1).…”

“…Perhaps more critical is the role of α-tetralones in synthesis, where they have been extensively exploited as versatile starting materials and intermediates in the generation of more complex molecules. [4][5][6][7][8][9] For instance, the industrial synthesis of the commonly prescribed selective serotonin reuptake inhibitor (SSRI) sertraline (4) proceeds via a critical αtetralone intermediate, dubbed sertraline tetralone (5, Scheme 1). [10] Classically, α-tetralones can be constructed using the Haworth reaction, which employs a Friedel-Crafts acylation with succinic anhydride followed by reduction of the subsequent aryl ketone and finally, an intramolecular Friedel-Crafts acylation.…”

An efficient approach for the synthesis of 6,7-dimethoxy-2-tetralone and 5,6-dimethoxy-1-tetralone

“…In some of these methods we have observed (i) long reaction sequences affording low to moderate yield, (ii) difficult experimental procedures which require skilled experimentalists to reproduce the results, (iii).the use of expensive reagents (rhodium, triphenylphosphonium chloride, ionic liquids etc) and (iv) the use of reagents (diazoketone,ethylene gas, βketosulfoxide etc) which are injurious for health. Analysing some of these draw backs and considering our interest on the synthesis of α and β-substituted tetralones 11 we believe that still a more efficient and facile synthesis can be developed for tetralones 1 and 2 which have proved to be potential intermediate for the synthesis of several bioactive compounds. We have sought a facile synthesis of the tetralones 1 and 2 by a single route instead of independent approach for each of these tetralones.…”