A general method for the synthesis of bastaranes and isobastaranes: first total synthesis of bastadins 5, 10, 12, 16, 20, and 21.
A general strategy for the synthesis of twenty naturally occurring bastadins (all but bastadin 3) is presented. A key retrosynthetic disconnection of the two amide bonds, common in all target molecules, bisects the macrocyclic core into two diaryl ether fragments, an alpha,omega-diamine (western part) and an alpha,omega-dicarboxylic acid (eastern part). Efficient preparation of the synthetically challenging o-mono or dibromo-substituted diaryl ether linkages was achieved employing the diaryl iodonium salt method. Regarding the western part, variations of the aliphatic chain were more efficiently secured by the preparation of two different alpha,omega-aminonitrile moieties. Cobalt boride mediated reduction of the nitrile functionality established the required diamines and, at the same time, provided the necessary variation of the aromatic-ring bromination pattern. Regarding the eastern part, two different dicarboxyl precursors had to be prepared in order to accommodate bromination-pattern variations. Coupling and subsequent macrolactamization of different combinations of these key intermediates may lead at will to any member of this family of marine natural products. Four bastaranes (bastadins 5, 10, 12 and 16) and two isobastaranes (bastadins 20 and 21) were synthesized as a demonstration of the flexibility and efficiency of the approach presented.
Couladouros
Elias A
EA
Chemistry Laboratories, Agricultural University of Athens, Iera Odos 75, GR 118 55 Athens, Greece. ecoula@chem.demokritos.gr
Pitsinos
Emmanuel N
EN
Moutsos
Vassilios I
VI
Sarakinos
Georgios
G
D001966:Bromine; D003035:Cobalt; D007202:Indicators and Reagents; D007769:Lactams; D008958:Models, Molecular; D008968:Molecular Conformation; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000737:chemistry*
D007202:Indicators and Reagents; D007769:Lactams; D010647:Phenyl Ethers; D003035:Cobalt; D001966:Bromine