Carbohydrate-based routes to salicylate natural products: formal total synthesis of (+)-apicularen A from d-glucal

A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products

“…4 The potent biological activity, structural novelty and limited availability of these salicylate anti-tumour natural products has resulted in the development of numerous synthetic approaches 5 culminating in recent total syntheses of salicylihalamide A by De Brabander et al, 6a Fürstner et al, 6b Labrecque et al, 6c Smith and Zheng 6d and Snider and Song, 6e of lobatamide C by Porco et al, 6f and of apicularen A by De Brabander's group, 6g together with a formal total synthesis of the latter compound. 7 This paper details the formal total synthesis of apicularen A using a carbohydrate based route. 7 -Glucal is used to prepare the protected, side-chain truncated macrolide (Ϫ)-6 (Scheme 1); (ϩ)-6 has been utilised by De Brabander et al during their total synthesis of apicularen A.…”

“…7 This paper details the formal total synthesis of apicularen A using a carbohydrate based route. 7 -Glucal is used to prepare the protected, side-chain truncated macrolide (Ϫ)-6 (Scheme 1); (ϩ)-6 has been utilised by De Brabander et al during their total synthesis of apicularen A. 5d, 6g We also report our findings concerning the base-induced ring opening of the tetrahydropyran ring in an apicularen intermediate.…”

Total Synthesis of Salicylihalamides A and B

“…R f = 0. 46 (petroleum ether/ethyl acetate, 3:1); [a] 1037, 1097, 1178, 1249, 1364, 1513, 2855, 2929, 2952, 3070 cm À1 ; MS (EI): m/z (%): 411 (2), 271 (3), 241 (10), 229 (46), 195 (5), 165 (8), 145 (14), 122 (14), 121 (100), 91 (13) -7-methyl-9-decene (25): Lithium triethylborohy-dride (1 m solution in THF, 0.55 mL, 0.55 mmol) was added dropwise to a cooled (0 8C) solution of tosylate 24 (100 mg, 154 mmol) in THF (1.5 mL). Stirring was continued for 12 h while the mixture was allowed to warm to room temperature.…”

“…In addition, formal total syntheses [13,14] and synthetic studies have been published. [15] A synthesis of salicylihalamide basically has to address three issues.…”

Synthesis of the Core Structure of Salicylihalamide A by Intramolecular Suzuki Reaction

“…From a synthetic point of view the benzolactone enamides represent challenging targets. In the meantime, total syntheses of apicularen A and salicylihalamide were reported. In addition, synthetic approaches to the core structure of these natural products 12,13 and studies aimed at the enamide side chains 14 have been published.…”