SYNTHETIC STUDIES ON OLIGOMYCINS - SYNTHESIS OF THE OLIGOMYCIN-B SPIROKETAL AND POLYPROPIONATE PORTIONS

The oligomycin B spiroketal portion, [2S,2(2R),3S,6R,8S,8(3R),9S,10R,1 1S]-2[2- ylsilyloxy)propyl]-8-[3(hydroxymethyl)pentyl]-3,9, 11-trimeth yl-1,7- dioxaspiro[5.5]undecane-5,10-diol (2), and polypropionate port ion, ethyl (2E,4S,5R,6R,7S,8S,9R,10S,12R,13S,14R,16E)-5-(t- ethylsilyl oxy)-7,9-(isopropylidenedioxy)-12,13-(4- ylidenedioxy)-4,6,8,10,12,14- hexamethyl-11-oxo-18- phenylsulfonyloctadeca-2,16-dienoate (3), have b een synthesized. The C19-C21 Wittig salt, [(2S,3R)-2-ethyl-3,4-(isopro pylidenedixoy)butyl]- triphenylphosphonium iodide (6), prepared from 2 -butene-1,4-diol via Sharpless epoixidation, was coupled with the C22- C27 aldehyde, benzyl yl-alpha,beta-L-galacto-hexodialdopyranoside-(1,5 ) (7), prepared from (Z)-2-butene-1,4-diol via Sharpless epoxidation a nd the Brown's crotylboration. The resulting coupling product was tran sformed to the C19-C27 lactone, ,6S,6(3R,4R)]-6-[3-ethyl-4,5-(isopropy lidenedixoy) xy)-3,5-dimethyl-3,4,5,6-tetrahydro-2H-pyran-2-one (4). T he C28-C34 organostannane compound, 4S,5S,7RS)-2-(t-butyldiphenylsilyl oxy)-5-methyl-7- (tributylstannyl)-4-(triethylsilyloxy)-7-[(2- trimeth ylsilylethoxy)-methoxy]heptane (5b), was prepared from (R)-methyl 3-hy droxybutyrate via the Brown's crotylboration and the Still's stannylat ion. After lithiation of 5b with butyllithium, the resulting alpha-alk oxy organolithium compound was coupled with 4 and the product was conv erted to the C19-C34 spiroketal, 8-[3-ethyl-4,5-(isopropylidenedioxy)p entyl]-10-(4- xy)-3,9,11-trimethyl-1,7-dioxaspiro[5.5]undecan-5- ol (3 7). The synthetic 2, derived from 37, was identical to the oligomycins (A, B, C mixture) degradation product in all respects, which elucidat es the absolute stereochemistry of oligomycin B (1b). the C3-C9 aldehy de, (2-trimethylsilylethoxy)methyl xy-3-O-(4-methoxybenzyl)-2,4,6-C-me thyl-D-glycero- alpha-L-ido-heptodialdopyranoside-(1,5) (9), was prepa red from (2S)-3-(t-butyldimethylsilyloxy)-2-methylpropanal via Keck's crotylstannane addition and Brown's crotylboration. The aldol coupling between the zinc enolate of the C10-C16 ketone, t-butyldimethylsilyl 3,5-di-C-methyl-alpha-L-xylo-octopyranosid-6-ulose (10), prepared from methyl (R)-(+)-lactate via Brown's crotylboration and a metallated me thoxyallene addition, and aldehyde 9 gave the C8-C9 syn, C9-C10 syn pr oduct, which was transformed to the oligomycin B polypropionate portio n 3 through elongation of the C1-C2 and C17-C18 carbon units.