Total synthesis of the marine sponge metabolites (+)-rottnestol, (+)-raspailol A and (+)-raspailol B.
The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.
Czuba
Ivona R
IR
School of Chemistry, The University of Melbourne, Victoria, 3010, Australia.
Zammit
Steven
S
Rizzacasa
Mark A
MA
D000475:Alkenes / Q000138:chemical synthesis*; D000818:Animals; D005663:Furans / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives; D009005:Monosaccharides / Q000138:chemical synthesis*; D009947:Organotin Compounds / Q000737:chemistry; D011090:Polyenes / Q000737:chemistry; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D005663:Furans; D009005:Monosaccharides; D009947:Organotin Compounds; D011090:Polyenes; C480999:raspailol A; C480998:raspailol B; C481000:rottnestol; D008697:Methane