A concise synthesis of the bioactive meroterpenoid natural product (±)-liphagal, a potent PI3K inhibitor

Total Syntheses of Liphagal: A Potent and Selective Phosphoinositide 3-Kinase α (PI3Kα) Inhibitor from the Marine Sponge Aka coralliphaga

“…To take the synthesis forward, installation of the formyl group was carried out by bromine/lithium exchange of a mixture of 5a and 5b (1:2. reported the formal total synthesis of (±)-1. 13 Their retrosynthetic plan is illustrated in Scheme 8, which is similar to that reported by Andersen et al 6 (see Scheme 3 in section 2-1-1). (17), which has already been converted to (±)-1, can be produced from brominated dienylbenzofuran 6 by biomimetic polyene cyclization followed by formylation on the aromatic ring (6 → 5 → 17).…”

“…VII → 1, pathway B in Scheme 1) by the Andersen, 6,15 Mehta, 13 Kumar, 14 and Ferreira 19 groups; ii) biomimetic ring expansion (pinacol-type rearrangement) approach (cf. IIIb → IVb, pathway A in Scheme 1) by the George, 11,12 Alvarez-Manzaneda, 16 and our 18 groups; and iii) nonbiomimetic approach (cf.…”

“…14 Their retrosynthetic plan is outlined in Scheme 12, which, for some reason, is almost the same as that described by Mehta et al 13 …”

“…Biosynthesis of corallidictyals A (3) and B (4) proposed by George et al 12 The unique structural features, attractive biological activities, limited availability from natural resources, and plausible biosynthetic pathway have made liphagal (1) an exceptionally intriguing and timely target for total synthesis. In 2006, the first total synthesis of racemic (±)-1 was presented by Andersen et al 6 Subsequently, the formal total syntheses of (±)-1 were reported by Mehta et al (2009) 13 and Kumar et al (2011), 17 and our group (2014). 18 Recently, the formal total synthesis of (±)-1 was reported by Ferreira et al (2017).…”

Is their potential for post-synthetic brominating reactions on benzene bridged PMOs?

“…Br 2 [30][31][32] 0.25 g benzene bridged PMO material was added to a threenecked flask, equipped with a condenser, and brought to reflux together with 50 mL of tetrachloromethane (Acros, 99%). Next, a catalytic amount of AlCl 3 (Acros, anhydrous, 99%) was added, followed by the addition of 0.3 mL of liquid bromine.…”